Well Integrity Mechanism, Failure, and Testing in Shallow Marine Sediments.

The leak-off test (LOT) is an in-situ method for testing casing shoe integrity in a well. It is used to evaluate the cement and formation integrity relative to the well plan specifications. The results determine whether any remedial cementing or corrective actions are required and are a basis for planning future wells in the area. Typical analysis of LOTs assumes an elastic wellbore and involves identification of linear trends on the recorded plots. However, LOTs recorded in shallow marine sediments (SMS) are inherently nonlinear and their analysis is a problem. Starting from the analyses of shallow soil properties, LOT plots, and leak-off pressure data, the dissertation presents the results of a theoretical study (analytical and numerical-finite element analysis) into potential for damage to cement integrity at the casing shoe resulting from leak-off test in SMS. Stress, strain and displacement around the open hole are analyzed before and during LOT. Three types of possible failures from LOTs were considered: vertical fracture, horizontal fracture, and cement parting. It is proved that vertical fracture is the most unlikely failure of the three. Although horizontal fractures are initiated at low pressure in the plastic zone around the wellbore, they cannot propagate beyond the plastic zone until wellbore pressures exceed overburden pressures. Cement parting, on the other hand, may propagate upwards at pressures lower than overburden pressure. The study identifies two factors, related directly to drilling technology, that control critical pressure of cement parting: contact stress and drilling fluid penetration. It is shown in the study that changes in cementing and drilling practices can improve casing shoe integrity and reduce the need for remedial cement squeezes. A general pressure-volume model of a LOT is presented including volumetric effects of wellbore expansion, mud loss into the rock, and propagation of both cement parting and plastic fracture. Software entitled LOTUMS was developed to simulate LOTs in SMS. A method is also proposed to identify the mechanisms controlling LOT results using known overburden pressure and the shape of LOT plot

Lung cancer gene expression database analysis incorporating prior knowledge with support vector machine-based classification method

<p>Abstract</p> <p>Background</p> <p>A reliable and precise classification is essential for successful diagnosis and treatment of cancer. Gene expression microarrays have provided the high-throughput platform to discover genomic biomarkers for cancer diagnosis and prognosis. Rational use of the available bioinformation can not only effectively remove or suppress noise in gene chips, but also avoid one-sided results of separate experiment. However, only some studies have been aware of the importance of prior information in cancer classification.</p> <p>Methods</p> <p>Together with the application of support vector machine as the discriminant approach, we proposed one modified method that incorporated prior knowledge into cancer classification based on gene expression data to improve accuracy. A public well-known dataset, Malignant pleural mesothelioma and lung adenocarcinoma gene expression database, was used in this study. Prior knowledge is viewed here as a means of directing the classifier using known lung adenocarcinoma related genes. The procedures were performed by software R 2.80.</p> <p>Results</p> <p>The modified method performed better after incorporating prior knowledge. Accuracy of the modified method improved from 98.86% to 100% in training set and from 98.51% to 99.06% in test set. The standard deviations of the modified method decreased from 0.26% to 0 in training set and from 3.04% to 2.10% in test set.</p> <p>Conclusion</p> <p>The method that incorporates prior knowledge into discriminant analysis could effectively improve the capacity and reduce the impact of noise. This idea may have good future not only in practice but also in methodology.</p

Comparison of linear discriminant analysis methods for the classification of cancer based on gene expression data

<p>Abstract</p> <p>Background</p> <p>More studies based on gene expression data have been reported in great detail, however, one major challenge for the methodologists is the choice of classification methods. The main purpose of this research was to compare the performance of linear discriminant analysis (LDA) and its modification methods for the classification of cancer based on gene expression data.</p> <p>Methods</p> <p>The classification performance of linear discriminant analysis (LDA) and its modification methods was evaluated by applying these methods to six public cancer gene expression datasets. These methods included linear discriminant analysis (LDA), prediction analysis for microarrays (PAM), shrinkage centroid regularized discriminant analysis (SCRDA), shrinkage linear discriminant analysis (SLDA) and shrinkage diagonal discriminant analysis (SDDA). The procedures were performed by software R 2.80.</p> <p>Results</p> <p>PAM picked out fewer feature genes than other methods from most datasets except from Brain dataset. For the two methods of shrinkage discriminant analysis, SLDA selected more genes than SDDA from most datasets except from 2-class lung cancer dataset. When comparing SLDA with SCRDA, SLDA selected more genes than SCRDA from 2-class lung cancer, SRBCT and Brain dataset, the result was opposite for the rest datasets. The average test error of LDA modification methods was lower than LDA method.</p> <p>Conclusions</p> <p>The classification performance of LDA modification methods was superior to that of traditional LDA with respect to the average error and there was no significant difference between theses modification methods.</p

Phosphatidylinositol 3-kinase inhibitor(LY294002) induces apoptosis of human nasopharyngeal carcinoma in vitro and in vivo

BACKGROUND: To evaluate whether PI3K/Akt pathway could effect on apoptosis and its mechanism in nasopharyngeal carcinoma cells. METHODS: The activation of the PI3K/Akt and its effect on CNE-2Z cells in vivo and in vitro was investigated by MTT assay, flow cytometry, western blot, ELISA, terminal deoxyribonucleotide transferase-mediated nick-end labeling assays (TUNEL), and immunohistochemical analyses, using PI3K inhibitor, LY294002. RESULTS: The results showed that LY294002 inhibited the phosphorylating of Akt (S473), cell proliferation, and induced apoptosis in CNE-2Z cells. However, our experiment results also demonstrated that apoptosis-induced LY294002 was directly regulated by caspase-9 activation pathway. CONCLUSION: These data suggested that PI3K inhibitor, LY294002, induced apoptosis by caspase-9 activation pathway and might be as a potentially useful target for therapeutic intervention in nasopharyngeal carcinoma patients

Reliability and accuracy of interview data in non-smoking female lung cancer case-control study

<p>Abstract</p> <p>Background</p> <p>Valid interview data is critical to the final results of the study. The purpose of this study was to investigate the reliability of epidemiological data obtained in non-smoking female lung cancer case-control study in China.</p> <p>Methods</p> <p>Fifty-six pairs of cases and controls, 10% percent of all the collected subjects were re-interviewed by three interviewers who underwent identical standardized training. A limited number of questions included in the original survey were asked again, the responses from the re-interview were compared with the original interview. Kappa was calculated by negative rates of agreement, positive rates of agreement and total rates of agreement to the accordance degree between the two interviews.</p> <p>Results</p> <p>The Kappa values were all more than 0.5 in all the studied indexes. The Kappa values descended from 0.92 in family history of cancer to 0.56 in oral contraception use. Errors in collecting and classifying data did occur, and were especially common for complicated clinical events, such as a drug exposure occurring many years before.</p> <p>Conclusion</p> <p>We identified four sources of this variability, three in collecting the data, and one in coding. As a result of these findings, strategies are proposed for improving the quality of interview data obtained in epidemiological research. Before finding a good solution, the strategy of data collecting and coding should be simple and easy to inspect.</p

Investigating the effects of climate variations on bacillary dysentery incidence in northeast China using ridge regression and hierarchical cluster analysis

<p>Abstract</p> <p>Background</p> <p>The effects of climate variations on bacillary dysentery incidence have gained more recent concern. However, the multi-collinearity among meteorological factors affects the accuracy of correlation with bacillary dysentery incidence.</p> <p>Methods</p> <p>As a remedy, a modified method to combine ridge regression and hierarchical cluster analysis was proposed for investigating the effects of climate variations on bacillary dysentery incidence in northeast China.</p> <p>Results</p> <p>All weather indicators, temperatures, precipitation, evaporation and relative humidity have shown positive correlation with the monthly incidence of bacillary dysentery, while air pressure had a negative correlation with the incidence. Ridge regression and hierarchical cluster analysis showed that during 1987–1996, relative humidity, temperatures and air pressure affected the transmission of the bacillary dysentery. During this period, all meteorological factors were divided into three categories. Relative humidity and precipitation belonged to one class, temperature indexes and evaporation belonged to another class, and air pressure was the third class.</p> <p>Conclusion</p> <p>Meteorological factors have affected the transmission of bacillary dysentery in northeast China. Bacillary dysentery prevention and control would benefit from by giving more consideration to local climate variations.</p

Case report: Resolution of Guillain-Barré syndrome in a patient with dual primary tumors after treatment with rituximab

Guillain-Barré syndrome (GBS) is a rare immune-related adverse event (irAE) that can occur in solid tumors such as hepatocellular carcinoma, gastric cancer, breast cancer, and colorectal cancer. It is characterized by progressive myasthenia and mild sensory abnormalities. The emergence of immune checkpoint inhibitors (ICIs) has significantly improved cancer patients’ life expectancy but can also trigger various irAEs, including GBS. We report a rare case of GBS in a 64-year-old male patient with dual primary tumors of the colon and stomach who received toripalimab and chemotherapy for liver metastases. After five treatments, the patient experienced weakness and numbness in his limbs. Lumbar puncture, electromyography, and other tests confirmed the diagnosis of GBS. Intravenous immunoglobulin (IVIG) and methylprednisolone did not improve the patient’s symptoms, but rituximab, which is not a standard regimen for GBS, was effective in eliminating B cells and improving symptoms. Following this, we effectively shifted from a regimen combining immunotherapy and chemotherapy to a targeted therapy regimen, resulting in prolonged patient survival. Currently, limited studies have been undertaken to evaluate the efficacy of rituximab in managing refractory neurological adverse events associated with ICI therapy. Using this case, we reviewed similar cases and formed our views

Tumor promoter TPA activates Wnt/β-catenin signaling in a casein kinase 1-dependent manner.

The tumor promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA) has been defined by its ability to promote tumorigenesis on carcinogen-initiated mouse skin. Activation of Wnt/β-catenin signaling has a decisive role in mouse skin carcinogenesis, but it remains unclear how TPA activates Wnt/β-catenin signaling in mouse skin carcinogenesis. Here, we found that TPA could enhance Wnt/β-catenin signaling in a casein kinase 1 (CK1) ε/δ-dependent manner. TPA stabilized CK1ε and enhanced its kinase activity. TPA further induced the phosphorylation of LRP6 at Thr1479 and Ser1490 and the formation of a CK1ε-LRP6-axin1 complex, leading to an increase in cytosolic β-catenin. Moreover, TPA increased the association of β-catenin with TCF4E in a CK1ε/δ-dependent way, resulting in the activation of Wnt target genes. Consistently, treatment with a selective CK1ε/δ inhibitor SR3029 suppressed TPA-induced skin tumor formation in vivo, probably through blocking Wnt/β-catenin signaling. Taken together, our study has identified a pathway by which TPA activates Wnt/β-catenin signaling