BackgroundBetter knowledge of the dose-toxicity relationship is essential for safe dose escalation to improve local control in cervical cancer radiotherapy. The conventional dose-toxicity model is based on the dose volume histogram, which is the parameter lacking spatial dose information. To overcome this limit, we explore a comprehensive rectal dose-toxicity model based on both dose volume histogram and dose map features for accurate radiation toxicity prediction.MethodsForty-two cervical cancer patients treated with combined external beam radiotherapy (EBRT) and brachytherapy (BT) were retrospectively studied, including 12 with Grade ≥ 2 rectum toxicity and 30 patients with Grade 0–1 toxicity (non-toxicity patients). The cumulative equivalent 2-Gy rectal surface dose was deformably summed using the deformation vector fields obtained through a recent developed local topology preserved non-rigid point matching algorithm. The cumulative three-dimensional (3D) dose was flattened and mapped to a two-dimensional (2D) plane to obtain the rectum surface dose map (RSDM). The dose volume parameters (DVPs) were calculated from the 3D rectum surface, while the texture features and the dose geometric parameters (DGPs) were extracted from the 2D RSDM. Representative features further computed from DVPs, textures and DGPs by principle component analysis (PCA) and statistical analysis were respectively fed into a support vector machine equipped with a sequential feature selection procedure. The predictive powers of the representative features were compared with the GEC-ESTRO dosimetric parameters D0.1/1/2cm3.ResultsSatisfactory predictive accuracy of sensitivity 74.75 and 84.75%, specificity 72.67 and 79.87%, and area under the receiver operating characteristic curve (AUC) 0.82 and 0.91 were respectively achieved by the PCA features and statistical significant features, which were superior to the D0.1/1/2cm3 (AUC 0.71). The relative area in dose levels of 64Gy, 67Gy, 68Gy, 87Gy, 88Gy and 89Gy, perimeters in dose levels of 89Gy, as well as two texture features were ranked as the important factors that were closely correlated with rectal toxicity.ConclusionsOur extensive experimental results have demonstrated the feasibility of the proposed scheme. A future large patient cohort study is still needed for model validation.Electronic supplementary materialThe online version of this article (10.1186/s13014-018-1068-0) contains supplementary material, which is available to authorized users.

When multiple imperfect dichotomous diagnostic tests are applied to an individual, it is possible that some or all of their results remain dependent even after conditioning on the true disease status. The estimates could be biased if this conditional dependence is ignored when using the test results to infer about the prevalence of a disease or the accuracies of the diagnostic tests. However, statistical methods correcting for this bias by modelling higher-order conditional dependence terms between multiple diagnostic tests are not well addressed in the literature. This paper extends a Bayesian fixed effects model for 2 diagnostic tests with pairwise correlation to cases with 3 or more diagnostic tests with higher order correlations. Simulation results show that the proposed fixed effects model works well both in the case when the tests are highly correlated and in the case when the tests are truly conditionally independent, provided adequate external information is available in the form of fixed constraints or prior distributions. A data set on the diagnosis of childhood pulmonary tuberculosis is used to illustrate the proposed model.

When two imperfect diagnostic tests are carried out on the same subject, their results may be correlated even after conditioning on the true disease status. While past work has focused on the consequences of ignoring conditional dependence, the degree to which conditional dependence can be induced has not been systematically studied. We examine this issue in detail by introducing a hypothetical missing covariate that affects the sensitivities of two imperfect dichotomous tests. We consider four forms for this covariate, normal, uniform, dichotomous and trichotomous. In the case of a dichotomous covariate, we derive an expression showing that the conditional covariance is a function of the product of the changes in test sensitivities (or specificities) between the subgroups defined by the covariate. The maximum possible covariance is induced by a dichotomous covariate with a very strong effect on both tests. Through simulations, we evaluate the extent to which fitting a latent class model ignoring each type of covariate but including a general covariance term can adjust for the correlation induced by the covariate. We compare the results to when the conditional dependence is ignored. We find that the bias because of ignoring conditional dependence is generally small even for moderate covariate effects, and when bias is present, a model including a covariance term works well. We illustrate our methods by analyzing data from a childhood tuberculosis study. Copyright © 2016 John Wiley & Sons, Ltd.

The status of K+ is important for plant health. However, little is known about if high-affinity potassium transporter HKTs may help K+ retention under salt stress. Here, we determined the effect of Arabidopsis thaliana transporter gene (AtHKT1) on the K+ status, Na+-induced toxicity, and salt tolerance in tobacco (Nicotiana tabacum L.). Six AtHKT1 transformed tobacco lines (T1, T2, … T6) were contrasted with a non-transgenic plantlet at the whole-plant and molecule levels. AtHKT1 gene was expressed in the xylems of stem, root and leaf vein in the transgenic tobacco, with the line T3 having highest expression. At Day 15, in the 200 mmol L−1 NaCl stress treatment, the transgenic plants remained a healthy K+ status, while the control plants decreased K+ content by 70% and Na+ contents in leaves and stems were 1.7 times that in the transgenic line. The AtHKT1 expression enhanced the activities of SOD, CAT and POD, raised chlorophyll and soluble sugar contents and root activity, and decreased MDA and proline contents and electrolyte leakage destruction. The constitutive over-expression of AtHKT1 that helps maintain a healthy K+ status while reducing Na+ toxicity may serve as a possible mechanism in maximizing productivity of tobacco under salt stress.

BackgroundRecently developed stereotactic partial breast irradiation (S-PBI) allows delivery of a high biologically potent dose to the target while sparing adjacent critical organs and normal tissue. With S-PBI tumoricidal doses, accurate and precise dose delivery is critical to achieve high treatment quality. This study is to investigate both rigid and non-rigid components of target geometric error and their corresponding margins in S-PBI and identify correlated clinical factors.MethodsForty-three early-stage breast cancer patients with implanted gold fiducial markers were enrolled in the study. Fiducial positions recorded on the orthogonal kV images on a Cyberknife system during treatment were used to estimate intra-fraction errors and composite errors (including intra-fraction errors and residual errors after patient setup). Both rigid and non-rigid components of intra-fraction and composite errors were analyzed and used to estimate rigid and non-rigid margins, respectively. Univariate and multivariate linear regressions were conducted to evaluate correlations between clinical factors and errors.ResultsFor the study group, the intra-fraction rigid and non-rigid errors are 2.0 ± 0.6 mm and 0.3 ± 0.2 mm, respectively. The composite rigid and non-rigid errors are 2.3 ± 0.5 mm and 1.3 ± 0.8 mm, respectively. The rigid margins in the left-right, anterior-posterior, and superior-inferior directions are estimated as 2.1, 2.4, and 2.3 mm, respectively. The estimated non-rigid margin, assumed to be isotropic, is 1.7 mm. The outer breast quadrants are more susceptible to composite errors occurrence than the inner breast quadrants. The target to chest wall distance is the clinical factor correlated with target geometric errors.ConclusionsThis is the first comprehensive analysis of breast target geometric rigid and non-rigid errors in S-PBI. Upon the estimation, the non-rigid margin is comparable to rigid margin, and therefore should be included in planning target volume as it cannot be accounted for by the Cyberknife system. Treatment margins selection also need to consider the impact of relevant clinical factor.Electronic supplementary materialThe online version of this article (10.1186/s13014-017-0889-6) contains supplementary material, which is available to authorized users.

BackgroundThe tuberculin skin test (TST) and interferon-gamma-release-assays (IGRAs) are utilized in screening programmes for presumed latent tuberculosis infection (LTBI) in health care workers (HCWs). However, inter-test comparison yields high rates of discordance, which is poorly understood. The aim of the study was therefore to identify factors associated with discordance amongst HCWs in a TB and HIV endemic setting.Methods505 HCWs were screened for LTBI in South Africa using the TST and two IGRA assays (QuantiFERON-TB-Gold-In-Tube (QFT-GIT) and TSPOT.TB). Factors associated with discordance were analyzed using a multinomial logistic regression model.ResultsTST-IGRA discordance was negatively associated with longer duration of employment for both TSPOT.TB (OR = 0.92; 95% confidence interval (CI) 0.85–0.99) and QFT-GIT (OR = 0.90; 95% CI 0.84–0.96). Marked test discordance occurred in HIV-infected individuals who were more likely to have TSPOT.TB + ve / TST-ve discordance (OR 4.44; 95% CI 1.14–17.27) or TSPOT.TB + ve / QFT-GIT-ve test discordance (OR 5.72; 95% CI 1.95–16.78). Those engaged in home care were less likely to have QFT-GIT + ve/TSPOT.TB -ve / discordance (OR 0.32; 95% CI 0.10–0.95).ConclusionThe marked TST-IGRA and IGRA-IGRA discordance in HIV-infected individuals suggest greater sensitivity of TSPOT.TB in immunocompromised persons or potential greater reactivity of TSPOT.TB in this population.

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In this paper, we consider some potential pitfalls of the growing use of quasi-likelihood-based information criteria for longitudinal data to select a working correlation structure in a generalized estimating equation framework. In particular, we examine settings where the fully conditional mean does not equal the marginal mean as well as hypothesis testing following selection of the working correlation matrix. Our results suggest that the use of any information criterion for selection of the working correlation matrix is inappropriate when the conditional mean model assumption is violated. We also find that type I error differs from the nominal level in moderate sample sizes following selection of the form of the working correlation but improves as sample size is increased as the selection is then concentrated on a single correlation structure. Our results serve to underline the potential dangers that can arise when using information criteria to select correlation structure in routine data analysis.