Flexible Modelling of Discrete Failure Time Including Time-Varying Smooth Effects

Discrete survival models have been extended in several ways. More flexible models are obtained by including time-varying coefficients and covariates which determine the hazard rate in an additive but not further specified form. In this paper a general model is considered which comprises both types of covariate effects. An additional extension is the incorporation of smooth interaction between time and covariates. Thus in the linear predictor smooth effects of covariates which may vary across time are allowed. It is shown how simple duration models produce artefacts which may be avoided by flexible models. For the general model which includes parametric terms, time-varying coefficients in parametric terms and time-varying smooth effects estimation procedures are derived which are based on the regularized expansion of smooth effects in basis functions

Localized Regression

The main problem with localized discriminant techniques is the curse of dimensionality, which seems to restrict their use to the case of few variables. This restriction does not hold if localization is combined with a reduction of dimension. In particular it is shown that localization yields powerful classifiers even in higher dimensions if localization is combined with locally adaptive selection of predictors. A robust localized logistic regression (LLR) method is developed for which all tuning parameters are chosen data¡adaptively. In an extended simulation study we evaluate the potential of the proposed procedure for various types of data and compare it to other classification procedures. In addition we demonstrate that automatic choice of localization, predictor selection and penalty parameters based on cross validation is working well. Finally the method is applied to real data sets and its real world performance is compared to alternative procedures

Generalized additive modelling with implicit variable selection by likelihood based boosting

The use of generalized additive models in statistical data analysis suffers from the restriction to few explanatory variables and the problems of selection of smoothing parameters. Generalized additive model boosting circumvents these problems by means of stagewise fitting of weak learners. A fitting procedure is derived which works for all simple exponential family distributions, including binomial, Poisson and normal response variables. The procedure combines the selection of variables and the determination of the appropriate amount of smoothing. As weak learners penalized regression splines and the newly introduced penalized stumps are considered. Estimates of standard deviations and stopping criteria which are notorious problems in iterative procedures are based on an approximate hat matrix. The method is shown to outperform common procedures for the fitting of generalized additive models. In particular in high dimensional settings it is the only method that works properly

Boosting Ridge Regression

Ridge regression is a well established method to shrink regression parameters towards zero, thereby securing existence of estimates. The present paper investigates several approaches to combining ridge regression with boosting techniques. In the direct approach the ridge estimator is used to fit iteratively the current residuals yielding an alternative to the usual ridge estimator. In partial boosting only part of the regression parameters are reestimated within one step of the iterative procedure. The technique allows to distinguish between variables that are always included in the analysis and variables that are chosen only if relevant. The resulting procedure selects variables in a similar way as the Lasso, yielding a reduced set of influential variables. The suggested procedures are investigated within the classical framework of continuous response variables as well as in the case of generalized linear models. In a simulation study boosting procedures for different stopping criteria are investigated and the performance in terms of prediction and the identification of relevant variables is compared to several competitors as the Lasso and the more recently proposed elastic net

Chemical composition of soil and vegetation of large petrochemical complex of Tobolsk

For the study, sites were selected that were located in the immediate vicinity of the construction site of a large petrochemical complex. The chemical composition of the total phytomass of monitoring sites was determined. The accumulation range, the most accumulated heavy metals and trace elements, varied within the limits: Zn (0,88-5,45); Cd (0.10-0.13); Co (0.20-0.18); Pb (0.42-0.52); Cr (0.14-1.48); Ni (1.72-5.19) mg / kg. The biogenic and salt compositions of the soil were studied. It was revealed that the soils of the plots are nonsaline, slightly acidic, biogenic elements are concentrated in the upper horizons

Harmonization of growth hormone measurements with different immunoassays by data adjustment

Background: The aim of our study was to evaluate the between-assay variability of commercially available immunoassays for the measurement of human growth hormone (hGH). In addition, we asked whether the comparability of the diagnosis of childhood onset growth hormone deficiency could be improved by adjusting hGH results by statistical methods, such as linear regression, conversion factors, and quantile transformation. Methods: In archived sera from 312 children and adolescents (age: 17 days-17 years) hGH values between 0.01 and 16.5 ng/mL were determined by using the following immunoassays: AutoDELFIA (PerkinElmer), BC-IRMA (Beckman-Coulter), ELISA (Mediagnost), IMMULITE 2000 (Siemens), iSYS (IDS), Liaison (DiaSorin), UniCel DxI 800 Access (BeckmanCoulter) and "In house"-RIA (Tubingen). Results: The assays differed in median hGH concentrations by as much as 5.44 ng/mL (Immulite), and as little as 2.67 ng/mL (BC-IRMA). The mean difference between assays ranged from 0.35 to 2.71 ng/mL, whereas several samples displayed differences up to 11.4 ng/mL. The best correlation (r=0.992) was found between AutoDELFIA and Liasion, the lowest (r=0.864) was between an in-house RIA and iSYS. The between-assay CV (mean +/- SD) of values within the cut-off range was 24.3%+/- 7.4%, resulting in an assay-dependent diagnosis of growth hormone deficiency (GHD) in more than 27% of patients. Yet, adjustment of this data by linear regression or a conversion factor reduced the CV below 14%, and the ratio of assay-dependent diagnoses below 8%. Using quantile transformation, the CV and ratio were reduced to 11.4% and < 1%, respectively. Conclusions: hGH measurements using different assays vary significantly. Linear regression, conversion factors, or particularly quantile transformation are useful tools to improve comparability in the diagnostic procedure for the confirmation of GHD in childhood and adolescence

On the Short-Time Compositional Stability of Periodic Multilayers

The short-time stability of concentration profiles in coherent periodic multilayers consisting of two components with large miscibility gap is investigated by analysing stationary solutions of the Cahn-Hilliard diffusion equation. The limits of the existence and stability of periodic concentration profiles are discussed as a function of the average composition for given multilayer period length. The minimal average composition and the corresponding layer thickness below which artificially prepared layers dissolve at elevated temperatures are calculated as a function of the multilayer period length for a special model of the composition dependence of the Gibbs free energy. For period lengths exceeding a critical value, layered structures can exist as metastable states in a certain region of the average composition. The phase composition in very thin individual layers, comparable with the interphase boundary width, deviates from that of the corresponding bulk phase.Comment: 29 pages including 7 figures, to be published in Thin Solid Film

Biological Significance of Anti-GH Antibodies in Children Treated with rhGH

Background: The occurrence of antidrug antibodies is common in children treated with recombinant human growth hormone (rhGH). However, their clinical significance is unclear. Objective: This study aimed to examine the clinical significance of anti-GH antibodies by analyzing the phenotype of patients who tested positive in relation to the quantity of anti-GH antibodies. Method: In this laboratory-based retrospective study encompassing a time span of 6 years, all positive samples were identified, and senders were contacted. Anti-GH antibodies were measured using a radioprecipitation assay; positive samples underwent a confirmatory assay. Results: Out of a total of 104 samples from 66 patients, positive test results were found in 28 samples from 13 patients. Clinical data were available from all but one. The group with positive test results comprised 6 patients with a normal response to GH provocative tests (group A) and 6 with an insufficient response or with isolated GH deficiency (IGHD) type 1A (group B). Diagnoses in group A were neurosecretory dysfunction, bioinactive GH syndrome and constitutional delay of growth and puberty. Diagnoses in group B were IGHD type 1A, septo-optic dysplasia, and cerebral midline defect with multiple pituitary hormone deficiency. Insufficient growth response to rhGH was absent except in one sibling pair with IGHD type 1A and a patient with cerebral midline defect. These patients had the highest concentrations of anti-GH antibodies. Conclusions: The biological significance of anti-GH antibodies seems to be limited to patients with high concentrations of anti-GH antibodies. For all other patients, we recommend a careful “wait and see” strategy and monitoring antibody titers

Graft-versus-Host disease Prophylaxis with Everolimus and Tacrolimus Is Associated with a High Incidence of Sinusoidal Obstruction Syndrome and Microangiopathy: Results of the EVTAC Trial

AbstractA calcineurin inhibitor combined with methotrexate is the standard prophylaxis for graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Everolimus, a derivative of sirolimus, seems to mediate antileukemia effects. We report on a combination of everolimus and tacrolimus in 24 patients (median age, 62 years) with either myelodysplastic syndrome (MDS; n = 17) or acute myeloid leukemia (AML; n = 7) undergoing intensive conditioning followed by HSCT from related (n = 4) or unrelated (n = 20) donors. All patients engrafted, and only 1 patient experienced grade IV mucositis. Nine patients (37%) developed acute grade II-IV GVHD, and 11 of 17 evaluable patients (64%) developed chronic extensive GVHD. Transplantation-associated microangiopathy (TMA) occurred in 7 patients (29%), with 2 cases of acute renal failure. The study was terminated prematurely because an additional 6 patients (25%) developed sinusoidal obstruction syndrome (SOS), which was fatal in 2 cases. With a median follow-up of 26 months, the 2-year overall survival rate was 47%. Although this new combination appears to be effective as a prophylactic regimen for acute GVHD, the incidence of TMA and SOS is considerably higher than seen with other regimens