Maximally selected chi-square statistics and binary splits of nominal variables

We address the problem of maximally selected chi-square statistics in the case of a binary Y variable and a nominal X variable with several categories. The distribution of the maximally selected chi-square statistic has already been derived when the best cutpoint is chosen from a continuous or an ordinal X, but not when the best split is chosen from a nominal X. In this paper, we derive the exact distribution of the maximally selected chi-square statistic in this case using a combinatorial approach. Applications of the derived distribution to variable selection and hypothesis testing are discussed based on simulations. As an illustration, our method is applied to a pregnancy and birth data set

Detection of Uniform and Non-Uniform Differential Item Functioning by Item Focussed Trees

Detection of differential item functioning by use of the logistic modelling approach has a long tradition. One big advantage of the approach is that it can be used to investigate non-uniform DIF as well as uniform DIF. The classical approach allows to detect DIF by distinguishing between multiple groups. We propose an alternative method that is a combination of recursive partitioning methods (or trees) and logistic regression methodology to detect uniform and non-uniform DIF in a nonparametric way. The output of the method are trees that visualize in a simple way the structure of DIF in an item showing which variables are interacting in which way when generating DIF. In addition we consider a logistic regression method in which DIF can by induced by a vector of covariates, which may include categorical but also continuous covariates. The methods are investigated in simulation studies and illustrated by two applications.Comment: 32 pages, 13 figures, 7 table

The BIOKLIM project: biodiversity research between climate change and wilding in a temperate montane forest : the conceptual framework

To understand the rapid rate of change in global biodiversity, it is necessary to analyse the present condition of ecosystems and to elucidate relationships of species to their environment. The BIOKLIM Project (Biodiversity and Climate Change Project) is intended to close this gap in our knowledge of montane and high montane forests of Central European low mountain ranges, one of the most threatened mixed montane systems worldwide. The Bavarian Forest National Park is characterised by its altitude range of ca. 800 m and a strongly developed gradient of forest structure. Relicts of old growth forests (areas of former local nature reserves) and dead stands, mostly killed by bark beetles, are accompanied by widely varying levels of woody debris and light. The gradients comprise a wide range of abiotic and forest structure factors, making the study area well suited for a multidisciplinary investigation of biodiversity. Unconstrained ordination (CA) of six taxa (vascular plants, wood inhabiting fungi, birds, carabids, spiders and molluscs) indicate the altitudinal gradient to be the main driver for distribution patterns of species assemblages. Objectives, structure, study design and data sampling of the BIOKLIM Project are described in detail. We set up 293 sampling plots along four main straight transects following the altitudinal gradient. All abiotic and stand structure data regarded as relevant are available for each plot. Vascular plants, wood inhabiting fungi and birds were sampled or mapped on all 293 plots. For the other 22 investigated taxa we used subsamples pre-stratified according to the sampling methods. The necessity of dealing with spatial autocorrelation, arising from sampling along linear transects, is described. Finally, study approach of our biodiversity project is compared with others involving altitudinal gradients. Worldwide, only a few multidisciplinary biodiversity studies have been previously conducted on long altitudinal gradients. However, in most cases sampling techniques were similar to ours, which allows comparison of results between continents. Keywords: Climate Change, Biodiversity, species-environment relationshipsUm die rasante Veränderung globaler Biodiversität zu verstehen, ist es erforderlich, den gegenwärtigen Zustand von Ökosystemen zu analysieren und die Zusammenhänge zwischen Arten und deren Umwelt aufzulösen. Das BIOKLIMProjekt (Biodiversität und Klima Projekt) hat zum Ziel, diese Wissenslücken für Wälder montaner und hochmontaner Mittelgebirge zu schließen. Der Nationalpark Bayerischer Wald ist neben dem Höhengradient (ca. 800 m) durch einen starken Strukturgradient geprägt. Dieser resultiert aus Restvorkommen sehr alter Bestände (ehem. Naturschutzgebiete) sowie dem Wirken des Borkenkäfers seit ca. zwei Jahrzehnten und einem dadurch verbundenen z. T. sehr hohen Totholzvorrat. Die Gradienten umfassen eine breite Spanne von abiotischen Faktoren und Bestandesstrukturen und machen den Nationalpark zu einem gut geeigneten Untersuchungsgebiet für interdisziplinäre Biodiversitätsforschung. Korrespondenzanalysen (CA) für 6 taxonomische Gruppen (Gefäßpflanzen, Holzpilze, Vögel, Laufkäfer, Spinnen und Mollusken) machen die starke Abhängigkeit der Artengruppen vom Höhengradienten deutlich. Es werden detailliert die Zielsetzungen, Projektaufbau, das Untersuchungsdesign sowie die Erfassungsmethoden des BIOKLIM-Projektes beschrieben. 293 Probepunkte wurden entlang von 4 Transekten, welche dem Höhengradienten folgen, eingerichtet. Zu jedem Probekreis stehen alle als relevant erachteten Daten zur Abiotik und Bestandesstruktur zur Verfügung. Gefäßpflanzen, Holzpilze und Vögel wurden auf allen 293 Probepunkten erfasst. Für die anderen 22 untersuchten Artengruppen wurde in Abhängigkeit von der Methode ein stratifiziertes Design gewählt. Lösungsansätze zum Umgang mit Autokorrelation, die durch die Anordnung von Probekreisen entlang von Linien (Transekte) bedingt ist, werden dargestellt. Schließlich wird das BIOKLIM-Projekt mit den wenigen weltweiten Biodiversitätsprojekten verglichen und diskutiert. In den meisten Fällen sind die Erhebungsmethoden ähnlich, sodass Vergleiche der Ergebnisse zwischen verschiedenen Kontinenten möglich werden. Schlüsselwörter: Klimawandel, Biodiversität, Arten-Umwelt-Beziehun

Predictive value of clinical and 18F-FDG-PET/CT derived imaging parameters in patients undergoing neoadjuvant chemoradiation for esophageal squamous cell carcinoma.

Aim of this study was to validate the prognostic impact of clinical parameters and baseline 18F-FDG-PET/CT derived textural features to predict histopathologic response and survival in patients with esophageal squamous cell carcinoma undergoing neoadjuvant chemoradiation (nCRT) and surgery. Between 2005 and 2014, 38 ESCC were treated with nCRT and surgery. For all patients, the 18F-FDG-PET-derived parameters metabolic tumor volume (MTV), SUVmax, contrast and busyness were calculated for the primary tumor using a SUV-threshold of 3. The parameter uniformity was calculated using contrast-enhanced computed tomography. Based on histopathological response to nCRT, patients were classified as good responders (< 10% residual tumor) (R) or non-responders (≥ 10% residual tumor) (NR). Regression analyses were used to analyse the association of clinical parameters and imaging parameters with treatment response and overall survival (OS). Good response to nCRT was seen in 27 patients (71.1%) and non-response was seen in 11 patients (28.9%). Grading was the only parameter predicting response to nCRT (Odds Ratio (OR) = 0.188, 95% CI: 0.040-0.883; p = 0.034). No association with histopathologic treatment response was seen for any of the evaluated imaging parameters including SUVmax, MTV, busyness, contrast and uniformity. Using multivariate Cox-regression analysis, the heterogeneity parameters busyness (Hazard Ratio (HR) = 1.424, 95% CI: 1.044-1.943; p = 0.026) and contrast (HR = 6.678, 95% CI: 1.969-22.643; p = 0.002) were independently associated with OS, while no independent association with OS was seen for SUVmax and MTV. In patients with ESCC undergoing nCRT and surgery, baseline 18F-FDG-PET/CT derived parameters could not predict histopathologic response to nCRT. However, the PET/CT derived features busyness and contrast were independently associated with OS and should be further investigated

miR-21, miR-99b and miR-375 combination as predictive response signature for preoperative chemoradiotherapy in rectal cancer.

INTRODUCTION: Preoperative chemoradiotherapy (CRT) is a standard treatment for locally advanced rectal cancer patients. Despite the benefits of CRT, its use in non-responder patients can be associated with increased toxicities and surgical resection delay. The identification of CRT response biomarkers, such as microRNAs, could improve the management of these patients. We have studied the microRNA expression in pretreatment endoscopy biopsies from rectal cancer patients treated with CRT to identify potential microRNAs able to predict CRT response and clinical outcome of these patients. MATERIAL AND METHODS: RNA from pretreatment endoscopy biopsies from 96 rectal cancer patients treated with preoperative CRT were studied. Pathological response was graded according to the tumor regression grade (TRG) Dworak classification. In the screening phase, 377 miRNAs were studied in 12 patients with extreme responses (TRG0-1 vs TRG4). The potential role as predictive biomarkers for CRT response, disease-free survival (DFS) and overall survival (OS) of the miRNAs identified in the screening phase were validated in the whole cohort. RESULTS: In the screening phase, an 8-miRNAs CRT-response signature was identified: let-7b, let-7e, miR-21, miR-99b, miR-183, miR-328, miR-375 and miR-483-5p. In the validation phase, miR-21, miR-99b and miR-375 emerged as CRT response-related miRNAs while miR-328 and let-7e emerged as prognostic markers for DFS and OS. Interestingly, ROC curve analysis showed that the combination of miR-21, miR-99b and miR-375 had the best capacity to distinguish patients with maximum response (TRG4) from others. CONCLUSIONS: miR-21, miR-99b and miR-375 could add valuable information for individualizing treatment in locally advanced rectal cancer patients

Immune senescence and immune activation in elderly colorectal cancer patients

In our previous study, we found that low thymic output and short telomere length were associated with a higher risk of tumor in elderly cancer patients. Here, we aimed to examine in depth the impact of immunological and biological senescence and immune activation on disease outcome in elderly patients with colorectal cancer (CRC).Peripheral blood samples from 81 CRC patients were studied for immune activation, immune senescence and recent thymic emigrant (RTE) CD4 and CD8 cells by flow cytometry. T-cell receptor rearrangement excision circle (TREC) levels and telomere lengths were measured by real-time PCR. Plasma levels of microbial translocation markers, LPS and sCD14, were quantified by ELISA. While TREC levels and telomere length were not prognostic of disease outcome, high percentages of immune senescent and immune activated CD8 cells were associated with a higher risk of a negative event (relapse, progression, or death) in all studied patients and disease relapse in I-Ill staged patients. Levels of sCD14 and LPS were higher in patients who will experience a negative event than in patients who will not. In conclusion, in elderly CRC patients higher immunological senescence and immune activation negatively impact the disease outcome; how these characteristics influence the antineoplastic treatments remains to be investigated