Parametric versus Nonparametric Treatment of Unobserved Heterogeneity in Multivariate Failure Times

Two contrary methods for the estimation of a frailty model of multivariate failure times are presented. The assumed Accelerated Failure Time Model includes censored data, observed covariates and unobserved heterogeneity. The parametric estimator maximizes the marginal likelihood whereas the method which does not require distributional assumptions combines the GEE approach (Liang and Zeger, 1986) with the Buckley-James (1979) estimator for censored data. Monte Carlo experiments are conducted to compare the methods under various conditions with regard to bias and efficiency. The ML estimator is found to be rather robust against some misspecifications and both methods seem to be interesting alternatives in uncertain circumstances which lack exact solutions. The methods are applied to data of recurrent purchase acts of yogurt brands

Cortical substrate of bladder control in SCI and the effect of peripheral pudendal stimulation

We investigate (i) the central representation of lower urinary tract (LUT) control and (ii–iii) the acute and 23 short-term central neuromodulatory effect of peripheral pudendal nerve stimulation in incomplete spinal 24 cord injured (SCI) patients using functional magnetic resonance imaging (fMRI). The urinary bladder of eight 25 SCI patients has been passively filled and emptied using a catheter, to identify the neural substrate of bladder 26 control (i), and with simultaneous peripheral pudendal nerve stimulation to investigate its acute central 27 neuromodulatory effect (ii). To identify the potential effects of pudendal nerve stimulation treatment (iii), 28 six patients underwent a 2-week training using pudendal nerve stimulation followed by another fMRI 29 session of bladder filling. The pre- and post-training fMRI results have been compared and correlated with 30 the patient's pre- and post-training urological status. Our results suggest that the central representation of 31 bladder filling sensation is preserved in the subacute stage of incomplete SCI. However, compared to earlier 32 data from healthy subjects, it shows decreased neural response in right prefrontal areas and increased in left 33 prefrontal regions, indicating diminished inhibitory micturition control as well as, compensatory or de- 34 compensatory reorganization of bladder control. We also provide evidence for a neuromodulatory effect of 35 acute pudendal nerve stimulation, which was most prominent in the right posterior insula, a brain region 36 implicated in homeostatic interoception in human. Pudendal stimulation training also induced significant 37 neuromodulation, predominantly signal increases, in the normal cortical network of bladder control. 38 Correlations with the patient's urological status indicate that this neuromodulatory effect may reflect the 39 clinical improvement following training

Parametric versus Nonparametric Treatment of Unobserved Heterogeneity in Multivariate Failure Times

Two contrary methods for the estimation of a frailty model of multivariate failure times are presented. The assumed Accelerated Failure Time Model includes censored data, observed covariates and unobserved heterogeneity. The parametric estimator maximizes the marginal likelihood whereas the method which does not require distributional assumptions combines the GEE approach (Liang and Zeger, 1986) with the Buckley-James (1979) estimator for censored data. Monte Carlo experiments are conducted to compare the methods under various conditions with regard to bias and efficiency. The ML estimator is found to be rather robust against some misspecifications and both methods seem to be interesting alternatives in uncertain circumstances which lack exact solutions. The methods are applied to data of recurrent purchase acts of yogurt brands

Ink Formulation for Printed Organic Electronics: Investigating Effects of Aggregation on Structure and Rheology of Functional Inks Based on Conjugated Polymers in Mixed Solvents

The utilization of solution‐processable organic semiconducting (OSC) polymers and the development of industrial‐relevant printing techniques enable cost‐efficient fabrication of optoelectronic devices for the mass market. Yet, the adaptation of viscoelastic properties of a functional ink to the respective printing technology is challenging. One crucial parameter is the formulation of the ink, which can be adjusted by selecting the combination of solvents that are mixed with the OSC. The current study considers model functional inks composed of a poly‐phenylene‐vinylene‐based OSC and two solvents, empirically known to be good. Their quality is quantified using the Hansen solubility parameters. The influence of the composition of the solvent mixture on structural, dynamical, and rheological behavior of the ink is investigated with light scattering, viscometry, and rheometry. Although both solvents are considered good, polymer aggregation is found at all compositions. Aggregation depends on composition in a nontrivial way. For dilute and semi‐dilute inks, the effects of aggregates on the ink viscosity are hidden by the difference in viscosities of the neat solvents. For elevated concentrations, the aggregates produce a hysteresis in the shear‐dependent viscosity, which should be considered when developing a functional ink for a particular printing technique

The operationalized psychodynamic diagnostics system. Clinical relevance, reliability and validity

In this paper, we present a multiaxial system for psychodynamic diagnosis, which has attained wide usage in Germany in the last 10 years. First we will discuss the 4 operationalized psychodynamic diagnostics (OPD) axes: illness experience and treatment assumptions, relationships, mental conflicts, and structure, then clinical applications will be outlined. Focus psychodynamic formulations can be employed both with inpatients and with outpatients. Studies show good reliability in a research context and acceptable reliability for clinical purposes. Validity will be separately summarized as content, criterion, and construct validity. Validity studies indicate good validity for the individual axes. Numerous studies on the OPD indicate areas of possible improvement, for example for clinical purposes the OPD should be more practically formulated

Encapsulated high temperature PCM as active filler material in a thermocline-based thermal storage system

A great concern in Concentrated Solar Power (CSP) is to boost energy harvesting systems, by finding materials with enhanced thermal performance. Phase Change Materials (PCM) have emerged as a promising option, due to their high thermal storage density compared to sensible storage materials currently used in CSP. A thermal storage system for solar power plants is proposed, a thermocline tank with PCM capsules together with filler materials, based on multi-layered solid-PCM (MLSPCM) thermocline-like storage tank concept [1,2]. A detailed selection of the most suitable high temperature PCM, their containment materials and encapsulation methods are shown

Ising Universality in Three Dimensions: A Monte Carlo Study

We investigate three Ising models on the simple cubic lattice by means of Monte Carlo methods and finite-size scaling. These models are the spin-1/2 Ising model with nearest-neighbor interactions, a spin-1/2 model with nearest-neighbor and third-neighbor interactions, and a spin-1 model with nearest-neighbor interactions. The results are in accurate agreement with the hypothesis of universality. Analysis of the finite-size scaling behavior reveals corrections beyond those caused by the leading irrelevant scaling field. We find that the correction-to-scaling amplitudes are strongly dependent on the introduction of further-neighbor interactions or a third spin state. In a spin-1 Ising model, these corrections appear to be very small. This is very helpful for the determination of the universal constants of the Ising model. The renormalization exponents of the Ising model are determined as y_t = 1.587 (2), y_h = 2.4815 (15) and y_i = -0.82 (6). The universal ratio Q = ^2/ is equal to 0.6233 (4) for periodic systems with cubic symmetry. The critical point of the nearest-neighbor spin-1/2 model is K_c=0.2216546 (10).Comment: 25 pages, uuencoded compressed PostScript file (to appear in Journal of Physics A

Anesthesia triggers drug delivery to experimental glioma in mice by hijacking caveolar transport

Abstract Background: Pharmaceutical intervention in the CNS is hampered by the shielding function of the blood-brain barrier (BBB). To induce clinical anesthesia, general anesthetics such as isoflurane readily penetrate the BBB. Here, we investigated whether isoflurane can be utilized for therapeutic drug delivery. Methods: Barrier function in primary endothelial cells was evaluated by transepithelial/transendothelial electrical resistance, and nanoscale STED and SRRF microscopy. In mice, BBB permeability was quantified by extravasation of several fluorescent tracers. Mouse models including the GL261 glioma model were evaluated by MRI, immunohistochemistry, electron microscopy, western blot, and expression analysis. Results: Isoflurane enhances BBB permeability in a time- and concentration-dependent manner. We demonstrate that, mechanistically, isoflurane disturbs the organization of membrane lipid nanodomains and triggers caveolar transport in brain endothelial cells. BBB tightness re-establishes directly after termination of anesthesia, providing a defined window for drug delivery. In a therapeutic glioblastoma trial in mice, simultaneous exposure to isoflurane and cytotoxic agent improves efficacy of chemotherapy. Conclusions: Combination therapy, involving isoflurane-mediated BBB permeation with drug administration has far-reaching therapeutic implications for CNS malignancies