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Weak Representation of the Cumulative Hazard Function under Semiparametric Random Censorship Models
(2001)
We study the estimation of some linear functionals which are based on an unknown lifetime distribution. The observations are assumed to be generated under the semi-parametric random censorship model (SRCM), that is, a random censorship model where the conditional expectation of the censoring indicator given the observation belongs to a parametric family. Under this setup a semi-parametric estimator of the survival function was introduced by the author. If the parametric model assumption is correct, it is known that the estimated functional which is based on this semi-parametric estimator is asymptotically at least as efficient as the corresponding one which rests on the nonparametric Kaplan–Meier estimator.
In this paper we show that the estimated functional which is based on this semi-parametric estimator is asymptotically efficient with respect to the class of all regular estimators under this semi-parametric model.
Based on an identifying Volterra type integral equation for randomly right censored observations from a lifetime distribution function F, we solve the corresponding estimating equation by an explicit and implicit Euler scheme. While the first approach results in some known estimators, the second one produces new semi-parametric and pre-smoothed Kaplan–Meier estimators which are real distribution functions rather than sub-distribution functions as the former ones are. This property of the new estimators is particular useful if one wants to estimate the expected lifetime restricted to the support of the observation time.
Specifically, we focus on estimation under the semi-parametric random censorship model (SRCM), that is, a random censorship model where the conditional expectation of the censoring indicator given the observation belongs to a parametric family. We show that some estimated linear functionals which are based on the new semi-parametric estimator are strong consistent, asymptotically normal, and efficient under SRCM. In a small simulation study, the performance of the new estimator is illustrated under moderate sample sizes. Finally, we apply the new estimator to a well-known real dataset.
This book provides a compact introduction to the bootstrap method. In addition to classical results on point estimation and test theory, multivariate linear regression models and generalized linear models are covered in detail. Special attention is given to the use of bootstrap procedures to perform goodness-of-fit tests to validate model or distributional assumptions. In some cases, new methods are presented here for the first time.
The text is motivated by practical examples and the implementations of the corresponding algorithms are always given directly in R in a comprehensible form. Overall, R is given great importance throughout. Each chapter includes a section of exercises and, for the more mathematically inclined readers, concludes with rigorous proofs. The intended audience is graduate students who already have a prior knowledge of probability theory and mathematical statistics.
This paper considers a paired data framework and discusses the question of marginal homogeneity of bivariate high-dimensional or functional data. The related testing problem can be endowed into a more general setting for paired random variables taking values in a general Hilbert space. To address this problem, a Cramér–von-Mises type test statistic is applied and a bootstrap procedure is suggested to obtain critical values and finally a consistent test. The desired properties of a bootstrap test can be derived that are asymptotic exactness under the null hypothesis and consistency under alternatives. Simulations show the quality of the test in the finite sample case. A possible application is the comparison of two possibly dependent stock market returns based on functional data. The approach is demonstrated based on historical data for different stock market indices.
A nonparametric goodness-of-fit test for random variables with values in a separable Hilbert space is investigated. To verify the null hypothesis that the data come from a specific distribution, an integral type test based on a Cramér-von-Mises statistic is suggested. The convergence in distribution of the test statistic under the null hypothesis is proved and the test's consistency is concluded. Moreover, properties under local alternatives are discussed. Applications are given for data of huge but finite dimension and for functional data in infinite dimensional spaces. A general approach enables the treatment of incomplete data. In simulation studies the test competes with alternative proposals.
Influence of refrigerated storage on tensile mechanical properties of porcine liver and spleen
(2015)
Reconstructive surgery and tissue replacements like ureters or bladders reconstruction have been recently studied, taking into account growth and remodelling of cells since living cells are capable of growing, adapting, remodelling or degrading and restoring in order to deform and respond to stimuli. Hence, shapes of ureters or bladders and their microstructure change during growth and these changes strongly depend on external stimuli such as training. We present the mechanical stimulation of smooth muscle cells in a tubular fibrin-PVDFA scaffold and the modelling of the growth of tissue by stimuli. To this end, mechanotransduction was performed with a kyphoplasty balloon catheter that was guided through the lumen of the tubular structure. The bursting pressure was examined to compare the stability of the incubated tissue constructs. The results showed the significant changes on tissues with training by increasing the burst pressure as a characteristic mechanical property and the smooth muscle cells were more oriented with uniformly higher density. Besides, the computational growth models also exhibited the accurate tendencies of growth of the cells under different external stimuli. Such models may lead to design standards for the better layered tissue structure in reconstructing of tubular organs characterized as composite materials such as intestines, ureters and arteries.
Zielführend moderieren
(2022)
In der Teamarbeit wird Moderation zum Erfolgsfaktor, der jedoch häufig unterschätzt wird. Ausgehend vom persönlichen Kompetenzniveau verknüpft dieses Buch Grundlagen und Methoden zu Wegen, um Ihre persönliche Entwicklung individuell zu begleiten: Neulinge finden hilfreiche Checklisten und Basistechniken für ihre ersten Moderationen, Fortgeschrittene wertvolle Praxistipps und Methoden für den Ausbau ihrer Moderationskompetenz. Profis schließlich genießen eine raffinierte Aussicht auf weniger bekannte Techniken und neue Anwendungen. Weiterführende Exkurse zum Meeting-Management und zur Online-Moderation runden den Anwendungshorizont ab.
Ob in Beruf, Studium oder Ehrenamt – derart ausgestattet gelingen Ihre eigene sowie die Entwicklung Ihres Teams durch zielführende Moderationen.
Damit Sie auch in den immer häufiger werdenden Onlineveranstaltungen als Moderator gut bestehen, sollten Sie wissen, was bei der Onlinemoderation im Besonderen zu beachten ist.
In diesem dritten Teil der Beitragsserie erfahren Sie, warum online anders als offline ist. Die technischen Möglichkeiten werden vorgestellt und auch wie diese zu nutzen sind. Schließlich erhalten Sie Tipps, die Sie beim Sprechen online beachten sollten.
Teamsitzungen, Arbeitsgruppentreffen, Kickoffs und Meetings – sie alle werden mit dem Ziel durchgeführt, innerhalb einer vorgegebenen Zeitspanne ein gemeinsames Arbeitsziel zu erreichen. Damit die Zielerreichung auch bei komplexeren Arbeitsaufträgen nicht vom Zufall abhängt, empfiehlt es sich, die Leitung des Ablaufs einem Moderator zu übertragen.
In diesem Beitrag einer mehrteiligen Serie wird beschrieben, über welches Mindset der Moderator verfügen sollte, welche grundsätzlichen Methoden hilfreich sind und was bei der Onlinemoderation im Besonderen zu beachten ist.
Damit Sie als Moderator effektiv und professionell moderieren können, sollten Sie die entsprechenden Methoden kennen.
Mit den richtigen Methoden können Sie Diskussionen leiten, Konflikte lösen, die Teilnehmer motivieren und dafür sorgen, dass die Ziele der Veranstaltung erreicht werden. Außerdem helfen sie Ihnen, eine positive Atmosphäre zu schaffen und das Interesse der Teilnehmer zu halten.
In diesem zweiten Beitrag der mehrteiligen Serie lernen Sie die grundsätzlichen Methoden kennen, um erfolgreiche Teamsitzungen, Arbeitsgruppentreffen, Kick-offs und Meetings durchzuführen.
Teamsitzungen, Arbeitsgruppentreffen, Kickoffs und Meetings – sie alle werden mit dem Ziel durchgeführt, innerhalb einer vorgegebenen Zeitspanne ein gemeinsames Arbeitsziel zu erreichen. Damit die Zielerreichung auch bei komplexeren Arbeitsaufträgen nicht vom Zufall abhängt, empfiehlt es sich, die Leitung des Ablaufs einem Moderator zu übertragen.
In diesem Beitrag einer mehrteiligen Serie wird beschrieben, über welches Mindset der Moderator verfügen sollte, welche grundsätzlichen Methoden hilfreich sind und was bei der Onlinemoderation im Besonderen zu beachten ist.
Teamsitzungen, Arbeitsgruppentreffen, Kickoffs und Meetings – sie alle werden mit dem Ziel durchgeführt, innerhalb einer vorgegebenen Zeitspanne ein gemeinsames Arbeitsziel zu erreichen. Damit die Zielerreichung auch bei komplexeren Arbeitsaufträgen nicht vom Zufall abhängt, empfiehlt es sich, die Leitung des Ablaufs einem Moderator zu übertragen.
In diesem Beitrag einer dreiteiligen Serie wird beschrieben, über welches Mindset der Moderator verfügen sollte, welche grundsätzlichen Methoden hilfreich sind und was bei der Onlinemoderation im Besonderen zu beachten ist.
Damit Sie als Moderator effektiv und professionell moderieren können, sollten Sie die entsprechenden Methoden kennen.
Mit den richtigen Methoden können Sie Diskussionen leiten, Konflikte lösen, die Teilnehmer motivieren und dafür sorgen, dass die Ziele der Veranstaltung erreicht werden. Außerdem helfen sie Ihnen, eine positive Atmosphäre zu schaffen und das Interesse der Teilnehmer zu halten.
In diesem zweiten Beitrag der mehrteiligen Serie lernen Sie die grundsätzlichen Methoden kennen, um erfolgreiche Teamsitzungen, Arbeitsgruppentreffen, Kick-offs und Meetings durchzuführen.
Damit Sie als Moderator effektiv und professionell moderieren können, sollten Sie die entsprechenden Methoden kennen.
Mit den richtigen Methoden können Sie Diskussionen leiten, Konflikte lösen, die Teilnehmer motivieren und dafür sorgen, dass die Ziele der Veranstaltung erreicht werden. Außerdem helfen sie Ihnen, eine positive Atmosphäre zu schaffen und das Interesse der Teilnehmer zu halten.
In diesem zweiten Beitrag der mehrteiligen Serie lernen Sie die grundsätzlichen Methoden kennen, um erfolgreiche Teamsitzungen, Arbeitsgruppentreffen, Kick-offs und Meetings durchzuführen.
Damit Sie auch in den immer häufiger werdenden Onlineveranstaltungen als Moderator gut bestehen, sollten Sie wissen, was bei der Onlinemoderation im Besonderen zu beachten ist.
In diesem dritten Teil der Beitragsserie erfahren Sie, warum online anders als offline ist. Die technischen Möglichkeiten werden vorgestellt und auch wie diese zu nutzen sind. Schließlich erhalten Sie Tipps, die Sie beim Sprechen online beachten sollten.
Magnetic nanoparticles (MNPs) are used as therapeutic and diagnostic agents for local delivery of heat and image contrast enhancement in diseased tissue. Besides magnetization, the most important parameter that determines their performance for these applications is their magnetic relaxation, which can be affected when MNPs immobilize and agglomerate inside tissues. In this letter, we investigate different MNP agglomeration states for their magnetic relaxation properties under excitation in alternating fields and relate this to their heating efficiency and imaging properties. With focus on magnetic fluid hyperthermia, two different trends in MNP heating efficiency are measured: an increase by up to 23% for agglomerated MNP in suspension and a decrease by up to 28% for mixed states of agglomerated and immobilized MNP, which indicates that immobilization is the dominant effect. The same comparatively moderate effects are obtained for the signal amplitude in magnetic particle spectroscopy.
Biomedical applications of magnetic nanoparticles (MNP) fundamentally rely on the particles’ magnetic relaxation as a response to an alternating magnetic field. The magnetic relaxation complexly depends on the interplay of MNP magnetic and physical properties with the applied field parameters. It is commonly accepted that particle core size is a major contributor to signal generation in all the above applications, however, most MNP samples comprise broad distribution spanning nm and more. Therefore, precise knowledge of the exact contribution of individual core sizes to signal generation is desired for optimal MNP design generally for each application. Specifically, we present a magnetic relaxation simulation-driven analysis of experimental frequency mixing magnetic detection (FMMD) for biosensing to quantify the contributions of individual core size fractions towards signal generation. Applying our method to two different experimental MNP systems, we found the most dominant contributions from approx. 20 nm sized particles in the two independent MNP systems. Additional comparison between freely suspended and immobilized MNP also reveals insight in the MNP microstructure, allowing to use FMMD for MNP characterization, as well as to further fine-tune its applicability in biosensing.
Many efforts are made worldwide to establish magnetic fluid hyperthermia (MFH) as a treatment for organ-confined tumors. However, translation to clinical application hardly succeeds as it still lacks of understanding the mechanisms determining MFH cytotoxic effects. Here, we investigate the intracellular MFH efficacy with respect to different parameters and assess the intracellular cytotoxic effects in detail. For this, MiaPaCa-2 human pancreatic tumor cells and L929 murine fibroblasts were loaded with iron-oxide magnetic nanoparticles (MNP) and exposed to MFH for either 30 min or 90 min. The resulting cytotoxic effects were assessed via clonogenic assay. Our results demonstrate that cell damage depends not only on the obvious parameters bulk temperature and duration of treatment, but most importantly on cell type and thermal energy deposited per cell during MFH treatment. Tumor cell death of 95% was achieved by depositing an intracellular total thermal energy with about 50% margin to damage of healthy cells. This is attributed to combined intracellular nanoheating and extracellular bulk heating. Tumor cell damage of up to 86% was observed for MFH treatment without perceptible bulk temperature rise. Effective heating decreased by up to 65% after MNP were internalized inside cells.
Heating efficiency of magnetic nanoparticles decreases with gradual immobilization in hydrogels
(2019)
Dual frequency magnetic excitation of magnetic nanoparticles (MNP) enables enhanced biosensing applications. This was studied from an experimental and theoretical perspective: nonlinear sum-frequency components of MNP exposed to dual-frequency magnetic excitation were measured as a function of static magnetic offset field. The Langevin model in thermodynamic equilibrium was fitted to the experimental data to derive parameters of the lognormal core size distribution. These parameters were subsequently used as inputs for micromagnetic Monte-Carlo (MC)-simulations. From the hysteresis loops obtained from MC-simulations, sum-frequency components were numerically demodulated and compared with both experiment and Langevin model predictions. From the latter, we derived that approximately 90% of the frequency mixing magnetic response signal is generated by the largest 10% of MNP. We therefore suggest that small particles do not contribute to the frequency mixing signal, which is supported by MC-simulation results. Both theoretical approaches describe the experimental signal shapes well, but with notable differences between experiment and micromagnetic simulations. These deviations could result from Brownian relaxations which are, albeit experimentally inhibited, included in MC-simulation, or (yet unconsidered) cluster-effects of MNP, or inaccurately derived input for MC-simulations, because the largest particles dominate the experimental signal but concurrently do not fulfill the precondition of thermodynamic equilibrium required by Langevin theory.
Magnetic nanoparticle relaxation in biomedical application: focus on simulating nanoparticle heating
(2021)
Frequency mixing magnetic detection (FMMD) is a sensitive and selective technique to detect magnetic nanoparticles (MNPs) serving as probes for binding biological targets. Its principle relies on the nonlinear magnetic relaxation dynamics of a particle ensemble interacting with a dual frequency external magnetic field. In order to increase its sensitivity, lower its limit of detection and overall improve its applicability in biosensing, matching combinations of external field parameters and internal particle properties are being sought to advance FMMD. In this study, we systematically probe the aforementioned interaction with coupled Néel–Brownian dynamic relaxation simulations to examine how key MNP properties as well as applied field parameters affect the frequency mixing signal generation. It is found that the core size of MNPs dominates their nonlinear magnetic response, with the strongest contributions from the largest particles. The drive field amplitude dominates the shape of the field-dependent response, whereas effective anisotropy and hydrodynamic size of the particles only weakly influence the signal generation in FMMD. For tailoring the MNP properties and parameters of the setup towards optimal FMMD signal generation, our findings suggest choosing large particles of core sizes dc > 25 nm nm with narrow size distributions (σ < 0.1) to minimize the required drive field amplitude. This allows potential improvements of FMMD as a stand-alone application, as well as advances in magnetic particle imaging, hyperthermia and magnetic immunoassays.
The hybrid K+/Ca2+ sensor based on laser scanned silicon transducer for multi-component analysis
(2002)
Purpose — to compare the chemical elemental composition of vitreous cavity content taken from cadaveric eyes compared to samples taken from the eyes with terminal stage refractory glaucoma with decompensated intraocular pressure (IOP). Material and methods. The vitreous contents of the eyes from 2 groups were studied. The 1st group included 15 cadaveric eyes; the 2nd group included 15 eyes with refractory glaucoma in the terminal stage of the disease with decompensated IOP in patients with hypertension pain. The vitreal content samples were taken in the course of antiglaucoma surgery aimed at preserving the eye as an organ and involving employment of drainage in the vitreous cavity. The study of virtual contents was carried out on energy dispersive spectrometer Oxford X-Max 50 integrated into scanning electron microscope Zeiss EVO LS10. Results. Increased concentrations of Kalium and Phosphorus were detected in the vitreous content of cadaveric eyes compared with the vitreal content from the eyes with terminal glaucoma with decompensated IOP taken in vivo (K — 0.172/0.093; P — 0.045/0.025 mmol/L). In the vitreous cavity in the eyes with end-stage glaucoma with decompensated IOP, the concentration of Nitrogen was higher in comparison with human cadaver eyes (2.030/1.424 mmol/L). Conclusion. The increased concentrations of Kalium and Phosphorus in the vitreous content of cadaveric eyes is associated with postmortem autolytic processes and with the release of intracellular content in the destruction of cell membranes. The increased Nitrogen concentration in the vitreal contents of the eyes with terminal stage glaucoma with decompensated IOP may be associated with the presence of osmotically active nitrogen-containing compounds in the eyes with increased IOP.
Optimization of passivation layers for corrosion protection of silicon-based microelectrode arrays
(2000)
Malaria infection remains a significant risk for much of the population of tropical and subtropical areas, particularly in developing countries. Therefore, it is of high importance to develop sensitive, accurate and inexpensive malaria diagnosis tests. Here, we present a novel aptamer-based electrochemical biosensor (aptasensor) for malaria detection by impedance spectroscopy, through the specific recognition between a highly discriminatory DNA aptamer and its target Plasmodium falciparum lactate dehydrogenase (PfLDH). Interestingly, due to the isoelectric point (pI) of PfLDH, the aptasensor response showed an adjustable detection range based on the different protein net-charge at variable pH environments. The specific aptamer recognition allows sensitive protein detection with an expanded detection range and a low detection limit, as well as a high specificity for PfLDH compared to analogous proteins. The specific feasibility of the aptasensor is further demonstrated by detection of the target PfLDH in human serum. Furthermore, the aptasensor can be easily regenerated and thus applied for multiple usages. The robustness, sensitivity, and reusability of the presented aptasensor make it a promising candidate for point-of-care diagnostic systems.
We present an electromechanically coupled Finite Element model for cardiac tissue. It bases on the mechanical model for cardiac tissue of Hunter et al. that we couple to the McAllister-Noble-Tsien electrophysiological model of purkinje fibre cells. The corresponding system of ordinary differential equations is implemented on the level of the constitutive equations in a geometrically and physically nonlinear version of the so-called edge-based smoothed FEM for plates. Mechanical material parameters are determined from our own pressure-deflection experimental setup. The main purpose of the model is to further examine the experimental results not only on mechanical but also on electrophysiological level down to ion channel gates. Moreover, we present first drug treatment simulations and validate the model with respect to the experiments.
We present an electromechanically coupled computational model for the investigation of a thin cardiac tissue construct consisting of human-induced pluripotent stem cell-derived atrial, ventricular and sinoatrial cardiomyocytes. The mechanical and electrophysiological parts of the finite element model, as well as their coupling are explained in detail. The model is implemented in the open source finite element code Code_Aster and is employed for the simulation of a thin circular membrane deflected by a monolayer of autonomously beating, circular, thin cardiac tissue. Two cardio-active drugs, S-Bay K8644 and veratridine, are applied in experiments and simulations and are investigated with respect to their chronotropic effects on the tissue. These results demonstrate the potential of coupled micro- and macroscopic electromechanical models of cardiac tissue to be adapted to experimental results at the cellular level. Further model improvements are discussed taking into account experimentally measurable quantities that can easily be extracted from the obtained experimental results. The goal is to estimate the potential to adapt the presented model to sample specific cell cultures.
Effectiveness of the edge-based smoothed finite element method applied to soft biological tissues
(2012)
Two single-incision mini-slings used for treating urinary incontinence in women are compared with respect to the stresses they produce in their surrounding tissue. In an earlier paper we experimentally observed that these implants produce considerably different stress distributions in a muscle tissue equivalent. Here we perform 2D finite element analyses to compare the shear stresses and normal stresses in the tissue equivalent for the two meshes and to investigate their failure behavior. The results clearly show that the Gynecare TVT fails for increasing loads in a zipper-like manner because it gradually debonds from the surrounding tissue. Contrary to that, the tissue at the ends of the DynaMesh-SIS direct may rupture but only at higher loads. The simulation results are in good agreement with the experimental observations thus the computational model helps to interpret the experimental results and provides a tool for qualitative evaluation of mesh implants.
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) today are widely used for the investigation of normal electromechanical cardiac function, of cardiac medication and of mutations. Computational models are thus established that simulate the behavior of this kind of cells. This section first motivates the modeling of hiPS-CM and then presents and discusses several modeling approaches of microscopic and macroscopic constituents of human-induced pluripotent stem cell-derived and mature human cardiac tissue. The focus is led on the mapping of the computational results one can achieve with these models onto mature human cardiomyocyte models, the latter being the real matter of interest. Model adaptivity is the key feature that is discussed because it opens the way for modeling various biological effects like biological variability, medication, mutation and phenotypical expression. We compare the computational with experimental results with respect to normal cardiac function and with respect to inotropic and chronotropic drug effects. The section closes with a discussion on the status quo of the specificity of computational models and on what challenges have to be solved to reach patient-specificity.