517 research outputs found

    Comparison of Artificial Neural Network and Logistic Regression Models for Predicting In-Hospital Mortality after Primary Liver Cancer Surgery

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    BACKGROUND: Since most published articles comparing the performance of artificial neural network (ANN) models and logistic regression (LR) models for predicting hepatocellular carcinoma (HCC) outcomes used only a single dataset, the essential issue of internal validity (reproducibility) of the models has not been addressed. The study purposes to validate the use of ANN model for predicting in-hospital mortality in HCC surgery patients in Taiwan and to compare the predictive accuracy of ANN with that of LR model. METHODOLOGY/PRINCIPAL FINDINGS: Patients who underwent a HCC surgery during the period from 1998 to 2009 were included in the study. This study retrospectively compared 1,000 pairs of LR and ANN models based on initial clinical data for 22,926 HCC surgery patients. For each pair of ANN and LR models, the area under the receiver operating characteristic (AUROC) curves, Hosmer-Lemeshow (H-L) statistics and accuracy rate were calculated and compared using paired T-tests. A global sensitivity analysis was also performed to assess the relative significance of input parameters in the system model and the relative importance of variables. Compared to the LR models, the ANN models had a better accuracy rate in 97.28% of cases, a better H-L statistic in 41.18% of cases, and a better AUROC curve in 84.67% of cases. Surgeon volume was the most influential (sensitive) parameter affecting in-hospital mortality followed by age and lengths of stay. CONCLUSIONS/SIGNIFICANCE: In comparison with the conventional LR model, the ANN model in the study was more accurate in predicting in-hospital mortality and had higher overall performance indices. Further studies of this model may consider the effect of a more detailed database that includes complications and clinical examination findings as well as more detailed outcome data

    IgG-class anti-PF4/heparin antibodies and symptomatic DVT in orthopedic surgery patients receiving different anti-thromboembolic prophylaxis therapeutics

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    <p>Abstract</p> <p>Background</p> <p>Heparin-induced thrombocytopenia (HIT) is a thromboembolic complication that can occur with unfractionated heparin (UFH) or low molecular weight heparin (LMWH). Our objective was to determine and compare the incidence of IgG-class HIT antibodies in patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) with different antithrombotic prophylaxis therapies and their contributions to the occurrence of venous thromboembolism (VTE).</p> <p>Methods</p> <p>A prospective observational study was performed for 374 Japanese patients undergoing THA or TKA to determine the incidence of VTE. IgG-class anti-PF4/heparin antibodies were measured using IgG-specific EIA before and after the operation.</p> <p>Results</p> <p>In the clinical outcome, the incidence of symptomatic deep vein thrombosis (DVT) was 15.0% (56/374, TKA; 35, THA; 21) and pulmonary emboli (PE) were not observed. The total seroconversion incidence of IgG-class PF4/heparin antibodies was 19.8% (74/374). The seroconversion incidence of IgG-class PF4/heparin antibodies was higher in patients receiving UFH (32.7%) compared to those receiving LMWH (9.5%) or fondaparinux (14.8%). Furthermore, the seroconversion incidence was significantly higher in patients undergoing TKA compared to those undergoing THA. Based on multivariate analysis, seroconversion of the IgG-class PF4/heparin antibodies was independent a risk factor for symptomatic DVT.</p> <p>Conclusion</p> <p>Our findings show that the seroconversion of IgG-class anti-PF4/heparin antibodies differed with various anti-thrombotic prophylaxis therapeutics and was associated with the risk of DVT in a subset of patients undergoing total joint arthroplasty (TKA and THA).</p

    Cultural factors that affected the spatial and temporal epidemiology of kuru

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    Kuru is a prion disease which became epidemic among the Fore and surrounding linguistic groups in Papua New Guinea, peaking in the late 1950s. It was transmitted during the transumption (endocannibalism) of dead family members at mortuary feasts. In this study, we aimed to explain the historical spread and the changing epidemiological patterns of kuru by analysing factors that affected its transmission. We also examined what cultural group principally determined a family’s behaviour during mortuary rituals. Our investigations showed that differences in mortuary practices were responsible for the initial pattern of the spread of kuru and the ultimate shape of the epidemic, and for subsequent spatio-temporal differences in the epidemiology of kuru. Before transumption stopped altogether, the South Fore continued to eat the bodies of those who had died of kuru, whereas other linguistic groups, sooner or later, stopped doing so. The linguistic group was the primary cultural group that determined behaviour but at linguistic boundaries the neighbouring group’s cultural practices were often adopted. The epidemiological changes were not explained by genetic differences, but genetic studies led to an understanding of genetic susceptibility to kuru and the selection pressure imposed by kuru, and provided new insights into human history and evolution

    The association of RANTES polymorphism with severe acute respiratory syndrome in Hong Kong and Beijing Chinese

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    <p>Abstract</p> <p>Background</p> <p>Chemokines play important roles in inflammation and antiviral action. We examined whether polymorphisms of <it>RANTES, IP-10 </it>and <it>Mig </it>affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS).</p> <p>Methods</p> <p>We tested the polymorphisms of <it>RANTES, IP-10 </it>and <it>Mig </it>for their associations with SARS in 495 Hong Kong Chinese SARS patients and 578 controls. Then we tried to confirm the results in 356 Beijing Chinese SARS patients and 367 controls.</p> <p>Results</p> <p><it>RANTES </it>-28 G allele was associated with SARS susceptibility in Hong Kong Chinese (<it>P </it>< 0.0001, OR = 2.80, 95%CI:2.11–3.71). Individuals with <it>RANTES </it>-28 CG and GG genotypes had a 3.28-fold (95%CI:2.32–4.64) and 3.06-fold (95%CI:1.47–6.39) increased risk of developing SARS respectively (<it>P </it>< 0.0001). This -28 G allele conferred risk of death in a gene-dosage dependent manner (<it>P </it>= 0.014) with CG and GG individuals having a 2.12-fold (95% CI: 1.11–4.06) and 4.01-fold (95% CI: 1.30–12.4) increased risk. For the replication of <it>RANTES </it>data in Beijing Chinese, the -28 G allele was not associated with susceptibility to SARS. However, -28 CG (OR = 4.27, 95%CI:1.64–11.1) and GG (OR = 3.34, 95%CI:0.37–30.7) were associated with admission to intensive care units or death due to SARS (<it>P </it>= 0.011).</p> <p>Conclusion</p> <p><it>RANTES </it>-28 G allele plays a role in the pathogenesis of SARS.</p

    Yeast Based Small Molecule Screen for Inhibitors of SARS-CoV

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    Severe acute respiratory coronavirus (SARS-CoV) emerged in 2002, resulting in roughly 8000 cases worldwide and 10% mortality. The animal reservoirs for SARS-CoV precursors still exist and the likelihood of future outbreaks in the human population is high. The SARS-CoV papain-like protease (PLP) is an attractive target for pharmaceutical development because it is essential for virus replication and is conserved among human coronaviruses. A yeast-based assay was established for PLP activity that relies on the ability of PLP to induce a pronounced slow-growth phenotype when expressed in S. cerevisiae. Induction of the slow-growth phenotype was shown to take place over a 60-hour time course, providing the basis for conducting a screen for small molecules that restore growth by inhibiting the function of PLP. Five chemical suppressors of the slow-growth phenotype were identified from the 2000 member NIH Diversity Set library. One of these, NSC158362, potently inhibited SARS-CoV replication in cell culture without toxic effects on cells, and it specifically inhibited SARS-CoV replication but not influenza virus replication. The effect of NSC158362 on PLP protease, deubiquitinase and anti-interferon activities was investigated but the compound did not alter these activities. Another suppressor, NSC158011, demonstrated the ability to inhibit PLP protease activity in a cell-based assay. The identification of these inhibitors demonstrated a strong functional connection between the PLP-based yeast assay, the inhibitory compounds, and SARS-CoV biology. Furthermore the data with NSC158362 suggest a novel mechanism for inhibition of SARS-CoV replication that may involve an unknown activity of PLP, or alternatively a direct effect on a cellular target that modifies or bypasses PLP function in yeast and mammalian cells

    Stereoselective handling of perhexiline:Implications regarding accumulation within the human myocardium

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    Purpose: Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine whether the acute accumulation of perhexiline in the myocardium is stereoselective and (2) investigate the relationship between duration of short-term therapy and the potential stereoselective effects of perhexiline within myocardium. Method: Patients (n = 129) from the active arm of a randomised controlled trial of preoperative perhexiline in cardiac surgery were treated with oral perhexiline for a median of 9 days. Correlates of atrial and ventricular concentrations of enantiomers were sought via univariate followed by multivariate analyses. Results: Myocardial uptake of both (+) and (βˆ’) perhexiline was greater in ventricles than in atria, and there was more rapid clearance of (βˆ’) than (+) perhexiline. The main determinants of atrial uptake of both (+) and (βˆ’) perhexiline were the plasma concentrations [(+) perhexiline: β =β€‰βˆ’0.256, p = 0.015; (βˆ’) perhexiline: β =β€‰βˆ’0.347, p = 0.001] and patients’ age [(+) perhexiline: β = 0.300, p = 0.004; (βˆ’) perhexiline: β = 0.288, p = 0.005]. Atrial uptake of (+) enantiomer also varied directly with duration of therapy (β = 0.228, p = 0.025), while atrial uptake of (βˆ’) perhexiline varied inversely with simultaneous heart rate (β =β€‰βˆ’0.240, p = 0.015). Conclusion: (1) Uptake of both perhexiline enantiomers into atrium is greater with advanced age and displays evidence of both saturability and minor stereoselectivity. (2) Atrial uptake of (βˆ’) perhexiline may selectively modulate heart rate reduction
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