| 1. |
- Andersson, Helene, 1983, et al.
(författare)
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The influence of the molecular weight of the water-soluble polymer on phase-separated films for controlled release
- 2016
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 511:1, s. 223-235
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxypropyl cellulose (HPC) and ethyl cellulose (EC) can be used for extended release coatings, where the water-soluble HPC may act as a pore former. The aim was to investigate the effect of the molecular weight of HPC on the microstructure and mass transport in phase-separated freestanding EC/HPC films with 30% w/w HPC. Four different HPC grades were used, with weight averaged molecular weights (Mw) of 30.0 (SSL), 55.0 (SL), 83.5 (L) and 365 (M) kg/mol. Results showed that the phase-separated structure changed from HPC-discontinuous to bicontinuous with increasing Mw of HPC. The film with the lowest Mw HPC (SSL) had unconnected oval-shaped HPC-rich domains, leaked almost no HPC and had the lowest water permeability. The remaining higher Mw films had connected complex-shaped pores, which resulted in higher permeabilities. The highest Mw film (M) had the smallest pores and very slow HPC leakage, which led to a slow increase in permeability. Films with grade L and SL released most of their HPC, yet the permeability of the L film was three times higher due to greater pore connectivity. It was concluded that the phase-separated microstructure, the level of pore percolation and the leakage rate of HPC will be affected by the choice of HPC Mw grade used in the film and this will in turn have strong impact on the film permeability.
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| 2. |
- Häbel, Henrike, 1987, et al.
(författare)
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A three-dimensional anisotropic point process characterization for pharmaceutical coatings
- 2017
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Ingår i: Spatial Statistics. - : Elsevier BV. - 2211-6753. ; 22:2, s. 306-320
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 Elsevier B.V. Spatial characterization and modeling of the structure of a material may provide valuable knowledge on its properties and function. Especially, for a drug formulation coated with a polymer film, understanding the relationship between pore structure and drug release properties is important to optimize the coating film design. Here, we use methods from image analysis and spatial statistics to characterize and model the pore structure in pharmaceutical coatings. More precisely, we use and develop point process theory to characterize the branching structure of a polymer blended film with data from confocal laser scanning microscopy. Point patterns, extracted by identifying branching points of pore channels, are both inhomogeneous and anisotropic. Therefore, we introduce a directional version of the inhomogeneous K-function to study the anisotropy and then suggest two alternative ways to model the anisotropic three-dimensional structure. First, we apply a linear transformation to the data such that it appears isotropic and subsequently fit isotropic inhomogeneous Strauss or Lennard-Jones models to the transformed pattern. Second, we include the anisotropy directly in a Lennard-Jones and a more flexible step-function model with anisotropic pair-potential functions. The methods presented will be useful for anisotropic inhomogeneous point patterns in general and for characterizing porous material in particular.
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| 3. |
- Häbel, Henrike, 1987
(författare)
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Characterization of Micro-Structures in Materials
- 2015
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- On developing the next generation sustainable soft materials, it is often crucial to understand and control their properties and function. Whereas a characterization of three-dimensional data is desirable in corresponding studies, often two-dimensional data are less time consuming to obtain. Consequently, characterizing the three-dimensional micro-structure of a material from two-dimensional data would enable efficient screening of its properties. In this work, the challenge of characterizing two different materials from two-dimensional images obtained by scanning (transmission) electron microscopy is overcome by using tools from image analysis and spatial statistics. The two different materials are a colloidal nanoparticle gel and a polymer blended film. The characterization of the micro-structures in the materials is conducted in two main steps. First, the microscopy images are processed in order to identify the objects of interest. Second, the structures are characterized according to the objects of interest. In particular, the spatial arrangement of nanoparticles is evaluated by summary functions from spatial statistics. One such function based on the size of a cluster of particles has been developed in this project. For the pore space analysis of a polymer blended film, tools from image analysis are applied to measure and compare the shapes of pores in a statistical analysis. The results obtained in this work, may be useful for reconstructions of the micro-structure in materials in three dimensions. Such reconstructions can be used to analyze materials, which may not yet have even been synthesized, in simulation studies without experiments involving valuable resources. In that way, new sustainable high quality products may be developed.
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| 4. |
- Häbel, Henrike, 1987, et al.
(författare)
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Characterization of pore structure of polymer blended films used for controlled drug release
- 2016
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 222, s. 151-158
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Tidskriftsartikel (refereegranskat)abstract
- The characterization of the pore structure in pharmaceutical coatings is crucial for understanding and controlling mass transport properties and function in controlled drug release. Since the drug release rate can be associated with the film permeability, the effect of the pore structure on the permeability is important to study. In this paper, a new approach for characterizing the pore structure in polymer blended films was developed based on an image processing procedure for given two-dimensional scanning electron microscopy images of film cross-sections. The focus was on different measures for characterizing the complexity of the shape of a pore. The pore characterization developed was applied to ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) blended films, often used as pharmaceutical coatings, where HPC acts as the pore former. It was studied how two different HPC viscosity grades influence the pore structure and, hence, mass transport through the respective films. The film with higher HPC viscosity grade had been observed to be more permeable than the other in a previous study; however, experiments had failed to show a difference between their pore structures. By instead characterizing the pore structures using tools from image analysis, statistically significant differences in pore area fraction and pore shape were identified. More specifically, it was found that the more permeable film with higher HPC viscosity grade seemed to have more extended and complex pore shapes than the film with lower HPC viscosity grade. This result indicates a greater degree of connectivity in the film with higher permeability and statistically confirms hypotheses on permeability from related experimental studies.
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| 5. |
- Häbel, Henrike, 1987, et al.
(författare)
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Colloidal particle aggregation in three dimensions
- 2019
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Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 275:3, s. 149-158
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Tidskriftsartikel (refereegranskat)abstract
- Colloidal systems are of importance not only for everyday products, but also for the development of new advanced materials. In many applications, it is crucial to understand and control colloidal interaction. In this paper, we study colloidal particle aggregation of silica nanoparticles, where the data are given in a three-dimensional micrograph obtained by high-angle annular dark field scanning transmission electron microscopy tomography. We investigate whether dynamic models for particle aggregation, namely the diffusion limited cluster aggregation and the reaction limited cluster aggregation models, can be used to construct structures present in the scanning transmission electron microscopy data. We compare the experimentally obtained silica aggregate to the simulated postaggregated structures obtained by the dynamic models. In addition, we fit static Gibbs point process models, which are commonly used models for point patterns with interactions, to the silica data. We were able to simulate structures similar to the silica structures by using Gibbs point process models. By fitting Gibbs models to the simulated cluster aggregation patterns, we saw that a smaller probability of aggregation would be needed to construct structures similar to the observed silica particle structure.
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| 6. |
- Häbel, Henrike, 1987
(författare)
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From experiments with images to 3D models
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- For developing the next generation sustainable materials, it is often crucial to understand and control their properties and function. This work presents cross-disciplinary research starting with experimentally fabricated porous soft biomaterials and images of their micro-structure obtained by electron or laser microscopy. It is investigated how much information on the three-dimensional material structure can be extracted from two-dimensional images and how conclusions compare to three-dimensional image analysis. Based on the image data, spatial statistical models are constructed and fitted to two different materials: a colloidal nanoparticle gel and a porous polymer blended film. Colloidal systems are everywhere in our everyday life and of high interest for the development of new advanced materials. Polymer films are popular for pharmaceutical coatings which control the release of a drug to obtain important therapeutic benefits. Besides presenting image analysis routines, three-dimensional finite Gibbs point processes with inhomogeneous and anisotropic pair-potential functions are introduced. Observed point patterns are formed by silica particle positions or pore branching points located at intersections of at least three pore channels. Due to physical chemical forces between particles and polymers, it is assumed that the points interact with each other. The pairwise interaction is described in the pair-potential function of a Gibbs process. In this way, there is a link between static Gibbs point process models and dynamic physical chemical processes like colloidal particle aggregation and polymer phase separation. Furthermore, a new spatial statistical summary function is suggested for the cluster size analysis on different length scales in aggregated structures. This function is a useful tool for comparing two regimes for particle aggregation resulting in different size and shape distributions of particle clusters. More precisely, it is used to study the diffusion limited and the reaction limited cluster aggregation. The methods introduced in this work can be applied to point processes in general and are important contributions to the point process literature. The results are useful for setting up a virtual design framework for the study of properties of various materials, which may not yet have even been synthesized, in simulation studies instead of experiments involving valuable resources.
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| 7. |
- Häbel, Henrike, 1987, et al.
(författare)
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From static micrographs to particle aggregation dynamics in three dimensions
- 2016
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Ingår i: Journal of Microscopy. - : Wiley. - 1365-2818 .- 0022-2720. ; 262:1, s. 102-111
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Tidskriftsartikel (refereegranskat)abstract
- Studies on colloidal aggregation have brought forth theories on stability of colloidal gels and models for aggregation dynamics. Still, a complete link between developed frameworks and obtained laboratory observations has to be found. In this work, aggregates of silica nanoparticles (20 nm) are studied using diffusion limited cluster aggregation (DLCA) and reaction limited cluster aggregation (RLCA) models. These processes are driven by the probability of particles to aggregate upon collision. This probability of aggregation is one in the DLCA and close to zero in the RLCA process. We show how to study the probability of aggregation from static micrographs on the example of a silica nanoparticle gel at 9 wt%. The analysis includes common summary functions from spatial statistics, namely the empty space function and Ripley's K-function, as well as two newly developed summary functions for cluster analysis based on graph theory. One of the new cluster analysis functions is related to the clustering coefficient in communication networks and the other to the size of a cluster. All four topological summary statistics are used to quantitatively compare in plots and in a least-square approach experimental data to cluster aggregation simulations with decreasing probabilities of aggregation. We study scanning transmission electron micrographs and utilize the intensity - mass thickness relation present in such images to create comparable micrographs from three-dimensional simulations. Finally, a characterization of colloidal silica aggregates and simulated structures is obtained, which allows for an evaluation of the cluster aggregation process for different aggregation scenarios. As a result, we find that the RLCA process fits the experimental data better than the DLCA process.
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| 8. |
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| 9. |
- Karimi, Mahssa, et al.
(författare)
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A sleep apnea related risk of vehicle accident is reduced by CPAP - Swedish traffic accident data acquisition (STRADA) registry
- 2014
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Ingår i: 22nd Congress of the European Sleep Research Society, 16–20 September 2014, Tallinn, Estonia. Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 23:Suppl 1, s. 67-67
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Obstructive sleep apnea (OSA) is associated with excessive daytime sleepiness (EDS) and two to seven times increased risk of motor vehicle accidents (MVAs) compared with the general population. The MVA rate in patients with suspected OSA, clinical features and the effect of treatment on risk prediction was investigated. Methods: Clinical sleep laboratory patients were cross-analyzed with a matched control group from the general population. The 10-year incidence of MVA among patients (n = 1478, 70.4% males, mean age 54 (13) years) and accidents (n = 21118) in the general population was analyzed. Risk factors associated with MVA risk were determined in patients with OSA. Results: Observed accidents among patients (n = 74) were compared with the expected number (n = 29.91, risk ratio 2.47, P < 0.001) predicted from the control population. Observed MVAs were more prevalent among younger (18–44 years) patiens but estimated OSA related excess accident risk was most prominent in elderly (65–80 years, risk ratio 3.5) drivers. Risk factors within the OSA patient cohort (high traffic exposure≥15 000 km/year, Epworth Sleepiness Score ≥16, habitual sleep time ≤5 h/night and use of hypnotics) were associated with increased accident risk (odds ratio 1.2, 2.1, 2.7 and 2.1, respectively, all P ≤ 0.03. Compliance with CPAP (≥4 h/night), was associated with a reduction of MVA frequency (7.6 to 2.5 accidents/1000 drivers/year). Conclusions: The motor vehicle accident risk in this large cohort of unselected sleep apnea patients suggests a need for accurate tools to identify individuals at risk. Conventional metrics of sleep apnea severity (e.g. apnea-hypopnea-index) failed to identify patients at risk.
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| 10. |
- Mattfeldt, T., et al.
(författare)
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Block bootstrap methods for the estimation of the intensity of a spatial point process with confidence bounds
- 2013
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Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 251:1, s. 84-98
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Tidskriftsartikel (refereegranskat)abstract
- This paper deals with the estimation of the intensity of a planar point process on the basis of a single point pattern, observed in a rectangular window. If the model assumptions of stationarity and isotropy hold, the method of block bootstrapping can be used to estimate the intensity of the process with confidence bounds. The results of two variants of block bootstrapping are compared with a parametric approximation based on the assumption of a Gaussian distribution of the numbers of points in deterministic subwindows of the original pattern. The studies were performed on patterns obtained by simulation of well-known point process models (Poisson process, two Matern cluster processes, Matern hardcore process, Strauss hardcore process). They were also performed on real histopathological data (point patterns of capillary profiles of 12 cases of prostatic cancer). The methods are presented as worked examples on two cases, where we illustrate their use as a check on stationarity (homogeneity) of a point process with respect to different fields of vision. The paper concludes with various methodological discussions and suggests possible extensions of the block bootstrap approach to other fields of spatial statistics.
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