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Objectives Identification of biomarkers associated with clinical benefit may be crucial in establishing optimal treatment choice for patients with squamous cell carcinoma (SCC) of the lung after first-line chemotherapy. In this study, the ability of the VeriStrat serum protein test to predict differential clinical benefit with afatinib versus erlotinib, and the association of VeriStrat status with clinical outcomes irrespective of EGFR-TKI used, was assessed in a retrospective analysis of the phase III LUX-Lung 8 trial. Materials and methods Pretreatment plasma samples were analyzed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Spectra were evaluated to assign a VeriStrat ‘Good’ (VS-G) or VeriStrat ‘Poor’ (VS-P) classification. Overall survival (OS), progression-free survival, and other endpoints were assessed with respect to pretreatment VeriStrat status; OS was the primary efficacy variable. Outcomes with other efficacy endpoints were similar. Results Of 795 patients randomized in LUX-Lung 8, 675 were classified (VS-G: 412; VS-P: 263). In the VS-G group, OS was significantly longer with afatinib versus erlotinib (HR 0.79 [95% CI: 0.63–0.98]). In the VS-P group, there was no significant difference in OS between afatinib and erlotinib (HR 0.90 [0.70–1.16]). However, there was no interaction between VeriStrat classification and treatment group for OS (pinteraction = 0.5303). OS was significantly longer in VS-G versus VS-P patients, both in the overall VeriStrat-classified population (HR 0.41 [0.35–0.49]) and afatinib-treated patients (HR 0.40 [0.31–0.51]). Multivariate analysis showed that VeriStrat was an independent predictor of OS in afatinib-treated patients, regardless of ECOG PS or best response to first-line chemotherapy. Conclusion VS-G classification is strongly associated with favorable survival outcomes with either afatinib or erlotinib compared with VS-P classification. In VS-G patients, survival outcomes with afatinib are superior to those with erlotinib. VeriStrat classification may guide treatment decisions in patients with SCC of the lung. ClinicalTrials.gov registration number: NCT01523587. © 2017

Homozygous mutations in the Cyclin dependent kinase 5 regulatory subunit-associated protein 2 geneCDK5RAP2cause primary autosomal recessive microcephaly (MCPH). MCPH is characterized by a pronounced reduction of brain volume, particularly of the cerebral cortex, and mental retardation. Though it is [for full text, please go to the a.m. URL], 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

Introduction: Implantation of textile meshes can cause severe complications like migration, erossion, shrinkage, deformation and fistula formation. In some of these cases the indication for surgical correction is beyond despute, but often “only” funtional problems or unspecific discomfort[for full text, please go to the a.m. URL], 128. Kongress der Deutschen Gesellschaft für Chirurgie

Background- Percutaneous cardiac interventions are currently performed under x-ray guidance. Magnetic resonance imaging (MRI) has been used to guide intravascular interventions in the past, but mainly in animals. Translation of MR-guided interventions into humans has been limited by the lack of MR-compatible and safe equipment, such as MR guide wires with mechanical characteristics similar to standard guide wires. The aim of the present study was to evaluate the safety and efficacy of a newly developed MR-safe and compatible passive guide wire in aiding MR-guided cardiac interventions in a swine model and describe the 2 first-in-man solely MR-guided interventions. Methods and Results- In the preclinical trial, the new MR-compatible wire aided the performance of 20 interventions in 5 swine. These consisted of balloon dilation of nondiseased pulmonary and aortic valves, aortic arch, and branch pulmonary arteries. After ethics and regulatory authority approval, the 2 first-in-man MR-guided interventions were performed in a child and an adult, both with elements of valvar pulmonary stenosis. Catheter manipulations were monitored with real-time MRI sequence with interactive modification of imaging plane and slice position. Temporal resolution was 11 to 12 frames/s. Catheterization procedure times were 110 and 80 minutes, respectively. Both patients had successful relief of the valvar stenosis and no procedural complications. Conclusions- The described preclinical study and case reports are encouraging that with the availability of the new MR-compatible and safe guide wire, certain percutaneous cardiac interventions will become feasible to perform solely under MR guidance in the future. A clinical trial is underway in our institution.

Objectives: To visualize the coronary sinus using magnetic resonance (MR), and to demonstrate the feasibility of MR-guided intubation of the cardiac venous system (CVS) in swine. Materials and Methods: A total of 6 pigs were investigated. All experiments were performed using an interventional 1.5-Tesla MRI system. The CVS was visualized using an inversion-recovery navigator-gated whole-heart steady-state free-precession sequence after administration of gadobenate dimeglumine contrast agent. The coronary sinus was then intubated under MR-guidance with a passive MR-compatible guidewire modified by incorporation of iron oxide markers for improved visualization and a nonbraided Cobra-catheter. MR-guided interventions were monitored using a steady-state free-precession real-time imaging sequence. Time needed was measured for MR-guided intubation of the CVS and compared with the time needed for fluoroscopy guided intubation of the CVS. Results: Visualization and intubation of the coronary sinus and its site branches was feasible in all cases. Time spent for MR-guided intubation of the CVS was comparable to time spent for fluoroscopy-guided intubation (8.2 ± 2 minutes vs. 8.3 ± 1.3 minutes; P = 0.85). Conclusions: MR-visualization and MR-guided intubation of the coronary sinus and its side branches is feasible. The feasibility of MR-guided intubation of the CVS might have relevance for procedures like cardiac resynchronization therapy and percutaneous transcatheter mitral annuloplasty, requiring improved 3-dimensional knowledge about cardiac vein anatomy in the near future.

Several feature types have been used with EEG-based Brain-Computer Interfaces Among the most popular are logarithmic band power estimates with more or less subject-specific optimization of file frequency bands. In this paper we introduce a feature called Time Domain Parameter that is defined by the generalization of the Hjorth parameters. Time Domain Parameters are Studied Under two different conditions. The first setting is defined when no data from a Subject is available. In this condition our results show that Time Domain Parameters outperform all band power features tested with all spatial filters applied. The second setting is the transition from calibration (no feedback) to feedback, in which the frequency content of the signals can change for some subjects We compare Time Domain Parameters with logarithmic band power in subject-specific bands and show that these features are advantageous in this situation as well.

Against the background that recent studies on embodied conversational agents demonstrate the importance of their behavior, an experimental study is presented that assessed the effects of different nonverbal behaviors of an embodied conversational agent on the users Ì experiences and evaluations as well as on their behavior. 50 participants conducted a conversation with different versions of the virtual agent Max, whose nonverbal communication was manipulated with regard to eyebrow movements and self- touching gestures. In a 2x2 between subjects design each behavior was varied in two levels: occurrence of the behavior compared to the absence of the behavior. Results show that self-touching gestures compared to no self-touching gestures have positive effects on the experiences and evaluations of the user, whereas eyebrow raising evoked less positive experiences and evaluations in contrast to no eyebrow raising. The nonverbal behavior of the participants was not affected by the agent's nonverbal behavior.

We propose a novel method to model nonlinear regression problems by adapting the principle of penalization to Partial Least Squares (PLS). Starting with a generalized additive model, we expand the additive component of each variable in terms of a generous amount of B-Splines basis functions. In order to prevent overfitting and to obtain smooth functions, we estimate the regression model by applying a penalized version of PLS. Although our motivation for penalized PLS stems from its use for B-Splines transformed data, the proposed approach is very general and can be applied to other penalty terms or to other dimension reduction techniques. It turns out that penalized PLS can be computed virtually as fast as PLS. We prove a close connection of penalized PLS to the solution of preconditioned linear systems. In the case of high-dimensional data, the new method is shown to be an attractive competitor to other techniques for estimating generalized additive models. If he number of predictor variables is high compared to the number of examples, traditional techniques often suffer from overfitting. We illustrate that penalized PLS performs well in these situations. - generalized additive model ; dimension reduction ; nonlinear regression ; conjugate gradient

The aim of this study was to investigate the effect of different light-curing units and irradiation modes on the mechanical fatigue strength and degree of conversion of a restorative resin composite. Conventional halogen, plasma arc and blue LED light-curing units were used for polymerization of a resin composite (Tetric® Ceram, Ivoclar, Vivadent, Liechtenstein). Initial fracture strength (FS) and flexural fatigue limit (FFL) as well as degree of conversion (DC) were measured. The FFL was determined under cyclic loading for 105 cycles in terms of a staircase approach. The specimens were stored for 14 days in 37 °C distilled water prior to testing. The curing efficiency was observed with Fourier transform infrared micromultiple internal reflectance spectroscopy. The measurements were carried out at 0.5 and 2.5 mm distance from the directly irradiated surface after 14 days storage in dark and dry conditions at 37 °C. The highest FS, FFL and DC were observed from high energy curing devices and from extended curing intervals. The conventional halogen light exhibited the most homogenous in-depth curing efficiency along with a low loss of mechanical resistance under cyclic fatigue. Evaluation of flexural fatigue limit and curing efficiency correlate in terms of decreased mechanical strength due to insufficient light-curing intervals or light intensities. Initial promising fracture strengths do not correlate with a clinically more relevant fatigue loading and with the in-depth degree of conversion, both accounting for a significantly reduced strength performance. © 2004 Academy Dental Materials. Published by Elsevier Ltd. All rights reserved.