Plan quality and robustness in field junction region for craniospinal irradiation with VMAT

PurposeTo propose a “staggered overlap” technique in volumetric modulated arc therapy (VMAT) for craniospinal irradiation (CSI) and compare the dose distribution and plan robustness with “overlap” technique and “gradient optimization” approach.Methods and Materials6 patients previously treated in our clinic were retrospectively selected. 9 VMAT plans of each patient were optimized with “staggered overlap”, “overlap” and “gradient optimization” in overlapping region of 3 cm, 6 cm, and 9 cm separately. For the “staggered overlap” plan, adjacent field sets were intentionally overlapped by staggering field edges in an appropriate step size to avoid sharp dose gradient. Evaluation metrics including V_95%, D_2%, D_98%, conformity number (CN) and homogeneity index (HI) were employed to evaluate the dose distribution. Moreover, shifts of the upper spinal field isocenter in each direction were performed to simulate junction errors for robustness analysis.ResultsThe CN and HI of VMAT plans with “staggered overlap” were 0.82 (0.811–0.822) and 0.113 (0.112–0.114), while they were 0.778 (0.776–0.782) and 0.131 (0.130–0.131) for plans with “gradient optimization”. In the robustness study, <3% dose deviations were found for 5 mm shifts in lateral and vertical directions with all techniques. In cranial-caudal direction, “overlap” technique created hot spots (D_2% > 170%) and cold spots (D_98% < 44%) in the junction region with 10 mm shifts. The dose deviations were decreased to 22% for plans with “staggered overlap” and 9 cm overlapping region.Conclusion“Staggered overlap” technique provides better plan quality as compared to “gradient optimization” approach and makes the plan more robust against junction errors as compared to “overlap” technique.     

Does a quorum sensing mechanism direct the behavior of immune cells?

Quorum sensing is a decision-making process used by decentralized groups such as colonies of bacteria to trigger a coordinated behavior. The existence of decentralized coordinated behavior has also been suggested in the immune system. In this paper, we explore the possibility for quorum sensing mechanisms in the immune response. Cytokines are good candidates as inducer of quorum sensing effects on migration, proliferation and differentiation of immune cells. The existence of a quorum sensing mechanism should be explored experimentally. It may provide new perspectives into immune responses and could lead to new therapeutic strategies.     

Robustness of Multiple Comparison Procedures: Treatment versus Control

Computer simulation techniques were used to investigate the Type I and Type II error rates of one parametric (Dunnett) and two nonparametric multiple comparison procedures for comparing treatments with a control under nonnormality and variance homogeneity. It was found that Dunnett's procedure is quite robust with respect to violations of the normality assumption. Power comparisons show that for small sample sizes Dunnett's procedure is superior to the nonparametric procedures also in non-normal cases, but for larger sample sizes the multiple analogue to Wilcoxon and Kruskal-Wallis rank statistics are superior to Dunnett's procedure in all considered nonnormal cases. Further investigations under nonnormality and variance heterogeneity show robustness properties with respect to the risks of first kind and power comparisons yield similar results as in the equal variance case.     

Robust Hotelling-Type T2 Statistics

To test an assumed mean vector, and to test the equality of two mean vectors, robust statistics are developed which have exactly the same form as the Hotelling T² statistics. These statistics are shown to have remarkable type I error robustness and power.     

Impact of environmental disturbances on estimated genetic parameters and breeding values for growth traits in pigs

Due to the diversification of farming systems and climate change, farm animals are exposed to environmental disturbances to which they respond differently depending on their robustness. Disturbances such as heat stress or sanitary challenges (not always recorded, especially when they are of short duration and low intensity) have a transitory impact on animals, resulting in changes in phenotypes of production (feed intake, BW, etc.). The aim of this study was to evaluate the impact of such unknown disturbances on the estimated genetic parameters and breeding values (BV) for production traits. A population of 6 120 individuals over five generations divided into eight batches of 10 pens was generated, each individual underwent an ?100-day test period. A longitudinal phenotype mimicking piglet weight during the fattening period was simulated for each individual in two situations: disturbed and non-disturbed. The disturbed phenotype was modified according to the robustness of the animal and the intensity and duration of the disturbance that the animal was subjected to. Various sets of simulations (1 000 replicates per set) were considered depending on the type of disturbance (at the level of the batch, pen, or individual), the genetic correlation (negative, neutral, or positive) between the two components of the robustness (resistance and resilience), the genetic correlation (negative, neutral, or positive) between growth and the components of robustness, and the heritability of the components of robustness (weak or moderate). An animal model was used to estimate the genetic parameters and BV for two production traits: the BW at 100 days of age (BW₁₀₀) and average daily gain (ADG). The estimated heritability of the production traits was lower in the disturbed situation compared to the non-disturbed one (reduction of 0.08 and 0.05 points respectively for BW₁₀₀ and ADG). The correlations between estimated breeding values of the observed phenotypes (EBV) and BV for production traits in absence of disturbance were lower in the disturbed situation (reduction of 0.04 and 0.06 points for BW₁₀₀ and ADG respectively) while the partial correlation between EBV and BV for robustness was not significantly different from 0 in the two situations. These results suggest that selection in a well-controlled environment with random disturbances of low intensities does not allow to improve animal robustness while it is less effective for improving production traits than selection under no environmental disturbances.     

Trade-Offs Between Efficiency and Robustness in Bacterial Metabolic Networks Are Associated with Niche Breadth

The relation between structure and function in biologic networks is a central point of systems biology research. Key functional features—notably, efficiency and robustness—are linked to the topologic structure of a network, and there appears to be a degree of trade-off between these features, i.e., simulation studies indicate that more efficient networks tend to be less robust. Here, we investigate this issue in metabolic networks from 105 lineages of bacteria having a wide range of ecologies. We take quantitative measurements on each network and integrate this network data with ecologic data using a phylogenetic comparative model. In this setting, we find that biologic conclusions obtained with classical phylogenetic comparative methods are sensitive to correlations between model covariates and phylogenetic branch length. To avoid this problem, we propose a revised statistical framework—hierarchical mixed-effect regression—to accommodate phylogenetic nonindependence. Using this approach, we show that the cartography of metabolic networks does indeed reflect a trade-off between efficiency and robustness. Furthermore, ecologic characteristics related to niche breadth are strong predictors of network shape. Given the broad variation in niche breadth seen among species, we predict that there is no universally optimal balance between efficiency and robustness in bacterial metabolic networks and, thus, no universally optimal network structure. These results highlight the biologic relevance of variation in network structure and the potential role of niche breadth in shaping metabolic strategies of efficiency and robustness. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Ransom A. Myers Died March 27th, 2007. He will be missed.     

On latent-variable model misspecification in structural measurement error models for binary response

Summary .  We consider structural measurement error models for a binary response. We show that likelihood-based estimators obtained from fitting structural measurement error models with pooled binary responses can be far more robust to covariate measurement error in the presence of latent-variable model misspecification than the corresponding estimators from individual responses. Furthermore, despite the loss in information, pooling can provide improved parameter estimators in terms of mean-squared error. Based on these and other findings, we create a new diagnostic method to detect latent-variable model misspecification in structural measurement error models with individual binary response. We use simulation and data from the Framingham Heart Study to illustrate our methods.     

A model for the spatiotemporal organization of DNA replication in <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis>

DNA replication in eukaryotes is considered to proceed according to a precise program in which each chromosomal region is duplicated in a defined temporal order. However, recent studies reveal an intrinsic temporal disorder in the replication of yeast chromosome VI. Here we provide a model of the chromosomal duplication to study the temporal sequence of origin activation in budding yeast. The model comprises four parameters that influence the DNA replication system: the lengths of the chromosomes, the explicit chromosomal positions for all replication origins as well as their distinct initiation times and the replication fork migration rate. The designed model is able to reproduce the available experimental data in form of replication profiles. The dynamics of DNA replication was monitored during simulations of wild type and randomly perturbed replication conditions. Severe loss of origin function showed only little influence on the replication dynamics, so systematic deletions of origins (or loss of efficiency) were simulated to provide predictions to be tested experimentally. The simulations provide new insights into the complex system of DNA replication, showing that the system is robust to perturbation, and giving hints about the influence of a possible disordered firing. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

基于独立元分析的脑磁图源定位

在脑磁图源定位问题中,通常感兴趣的是脑内众多神经活动源中的一个或几个,而传统源定位方法,如多信号分类方法,需要将所有源的位置都确定后,通过重组信号波形才能获得所感兴趣源的位置信息。为了提高定位效率,文章作者提出了一种结合独立元分析的脑磁图源定位方法。实验结果表明,该方法能加快定位的速度,同时能够在一定程度上克服噪声的影响,具有更强的抗噪声能力。