| 1. |
- Andersson, Claes, 1987, et al.
(author)
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A Bayesian hierarchical point process model for epidermal nerve fiber patterns
- 2019
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In: Mathematical Biosciences. - : Elsevier BV. - 1879-3134 .- 0025-5564. ; 313, s. 48-60
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Journal article (peer-reviewed)abstract
- We introduce the Thomas process in a Bayesian hierarchical setting as a model for point pattern data with a nested structure. This model is applied to a nerve fiber data set which consists of several point patterns of nerve entry points from 47 subjects divided into 3 groups, where the grouping is based on the diagnosed severity of a certain nerve disorder. The modeling assumption is that each point pattern is a realization of a Thomas process, with parameter values specific to the subject. These parameter values are in turn assumed to come from distributions that depend on which group the subject belongs to. To fit the model, we construct an MCMC algorithm, which is evaluated in a simulation study. The results of the simulation study indicate that the group level mean of each parameter is well estimated, but that the estimation of the between subject variance is more challenging. When fitting the model to the nerve fiber data, we find that the structure within clusters appears to be the same in all groups, but that the number of clusters decreases with the progression of the nerve disorder.
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| 2. |
- Andersson, Claes, 1987, et al.
(author)
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Discovering early diabetic neuropathy from epidermal nerve fiber patterns
- 2016
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In: Statistics in Medicine. - : Wiley. - 0277-6715 .- 1097-0258. ; 35:24, s. 4427-4442
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Journal article (peer-reviewed)abstract
- Epidermal nerve fibre (ENF) density and morphology are used to study small fibre involvement in diabetic, HIV, chemotherapy induced and other neuropathies. ENF density and summed length of ENFs per epidermal surface area are reduced, and ENFs may appear more clustered within the epidermis in subjects with small fibre neuropathy than in healthy subjects. Therefore, it is important to understand the spatial structure of ENFs. In this paper, we compare the ENF patterns between healthy subjects and subjects suffering from mild diabetic neuropathy. The study is based on suction skin blister specimens from the right foot of 32 healthy subjects and eight subjects with mild diabetic neuropathy. We regard the ENF entry point (location where the trunks of a nerve enters the epidermis) and ENF end point (termination of the nerve fibres) patterns as realizations of spatial point processes, and develop tools that can be used in the analysis and modelling of ENF patterns. We use spatial summary statistics and shift plots and define a new tool, reactive territory, to study the spatial patterns and to compare the patterns of the two groups. We will also introduce a simple model for these data in order to understand the growth process of the nerve fibres.
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| 3. |
- Andersson, Claes, 1987, et al.
(author)
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Hierarchical models for epidermal nerve fiber data
- 2018
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In: Statistics in Medicine. - : Wiley. - 0277-6715 .- 1097-0258. ; 37:3, s. 357-374
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Journal article (peer-reviewed)abstract
- While epidermal nerve fiber (ENF) data have been used to study the effects of small fiber neuropathies through the density and the spatial patterns of the ENFs, little research has been focused on the effects on the individual nerve fibers. Studying the individual nerve fibers might give a better understanding of the effects of the neuropathy on the growth process of the individual ENFs. In this study, data from 32 healthy volunteers and 20 diabetic subjects, obtained from suction induced skin blister biopsies, are analyzed by comparing statistics for the nerve fibers as a whole and for the segments that a nerve fiber is composed of. Moreover, it is evaluated whether this type of data can be used to detect diabetic neuropathy, by using hierarchical models to perform unsupervised classification of the subjects. It is found that using the information about the individual nerve fibers in combination with the ENF counts yields a considerable improvement as compared to using the ENF counts only. Copyright © 2017 John Wiley & Sons, Ltd.
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| 4. |
- Bolin, David, 1983, et al.
(author)
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Statistical Prediction of Global Sea Level From Global Temperature
- 2015
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In: Statistica Sinica. - : Statistica Sinica (Institute of Statistical Science). - 1017-0405. ; 25:1, s. 351-367
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Journal article (peer-reviewed)abstract
- Sea level rise is a threat to many coastal communities, and projection of future sea level for different climate change scenarios is an important societal task In this paper, we first construct a time series regression model to predict global sea level from global temperature. The model is fitted to two sea level data sets (with and without corrections for reservoir storage of water) and three temperature data sets. The effect of smoothing before regression is also studied. Finally, we apply a novel methodology to develop confidence bands for the projected sea level, simultaneously for 2000-2100, under different scenarios, using temperature projections from the latest climate modeling experiment. The main finding is that different methods for sea level projection, which appear to disagree, have confidence intervals that overlap, when taking into account the different sources of variability in the analyses.
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| 5. |
- Carmona, Pierre, 1995, et al.
(author)
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Controlling the structure of spin-coated multilayer ethylcellulose/ hydroxypropylcellulose films for drug release
- 2023
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In: International Journal of Pharmaceutics. - 0378-5173 .- 1873-3476. ; 644
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Journal article (peer-reviewed)abstract
- Porous phase-separated ethylcellulose/hydroxypropylcellulose (EC/HPC) films are used to control drug transport out of pharmaceutical pellets. Water-soluble HPC leaches out and forms a porous structure that controls the drug transport. Industrially, the pellets are coated using a fluidized bed spraying device, and a layered film exhibiting varying porosity and structure after leaching is obtained. A detailed understanding of the formation of the multilayered, phase-separated structure during production is lacking. Here, we have investigated multilayered EC/HPC films produced by sequential spin-coating, which was used to mimic the industrial process. The effects of EC/HPC ratio and spin speed on the multilayer film formation and structure were investigated using advanced microscopy techniques and image analysis. Cahn-Hilliard simulations were performed to analyze the mixing behavior. A gradient with larger structures close to the substrate surface and smaller structures close to the air surface was formed due to coarsening of the layers already coated during successive deposition cycles. The porosity of the multilayer film was found to vary with both EC/HPC ratio and spin speed. Simulation of the mixing behavior and in situ characterization of the structure evolution showed that the origin of the discontinuities and multilayer structure can be explained by the non-mixing of the layers.
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| 6. |
- Carmona, Pierre, 1995, et al.
(author)
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Cross-sectional structure evolution of phase-separated spin-coated ethylcellulose/hydroxypropylcellulose films during solvent quenching
- 2022
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In: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 12:40, s. 26078-26089
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Journal article (peer-reviewed)abstract
- Porous phase-separated ethylcellulose/hydroxypropylcellulose (EC/HPC) films are used to control drug transport out of pharmaceutical pellets. The films are applied on the pellets using fluidized bed spraying. The drug transport rate is determined by the structure of the porous films that are formed as the water-soluble HPC leaches out. However, a detailed understanding of the evolution of the phase-separated structure during production is lacking. Here, we have investigated EC/HPC films produced by spin-coating, which mimics the industrial manufacturing process. This work aimed to understand the structure formation and film shrinkage during solvent evaporation. The cross-sectional structure evolution was characterized using confocal laser scanning microscopy (CLSM), profilometry and image analysis. The effect of the EC/HPC ratio on the cross-sectional structure evolution was investigated. During shrinkage of the film, the phase-separated structure undergoes a transition from 3D to nearly 2D structure evolution along the surface. This transition appears when the typical length scale of the phase-separated structure is on the order of the thickness of the film. This was particularly pronounced for the bicontinuous systems. The shrinkage rate was found to be independent of the EC/HPC ratio, while the initial and final film thickness increased with increasing HPC fraction. A new method to estimate part of the binodal curve in the ternary phase diagram for EC/HPC in ethanol has been developed. The findings of this work provide a good understanding of the mechanisms responsible for the morphology development and allow tailoring of thin EC/HPC films structure for controlled drug release.
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| 7. |
- Carmona, Pierre, 1995, et al.
(author)
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Structure evolution during phase separation in spin-coated ethylcellulose/hydroxypropylcellulose films
- 2021
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In: Soft Matter. - : Royal Society of Chemistry. - 1744-683X .- 1744-6848. ; 17:14, s. 3913-3922
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Journal article (peer-reviewed)abstract
- Porous phase-separated films made of ethylcellulose (EC) and hydroxypropylcellulose (HPC) are commonly used for controlled drug release. The structure of these thin films is controlling the drug transport from the core to the surrounding liquids in the stomach or intestine. However, detailed understanding of the time evolution of these porous structures as they are formed remains elusive. In this work, spin-coating, a widely applied technique for making thin uniform polymer films, was used to mimic the industrial manufacturing process. The focus of this work was on understanding the structure evolution of phase-separated spin-coated EC/HPC films. The structure evolution was determined using confocal laser scanning microscopy (CLSM) and image analysis. In particular, we determined the influence of spin-coating parameters and EC : HPC ratio on the final phase-separated structure and the film thickness. The film thickness was determined by profilometry and it influences the ethanol solvent evaporation rate and thereby the phase separation kinetics. The spin speed was varied between 1000 and 10 000 rpm and the ratio of EC : HPC in the polymer blend was varied between 78 : 22 wt% and 40 : 60 wt%. The obtained CLSM micrographs showed phase separated structures, typical for the spinodal decomposition phase separation mechanism. By using confocal laser scanning microscopy combined with Fourier image analysis, we could extract the characteristic length scale of the phase-separated final structure. Varying spin speed and EC : HPC ratio gave us precise control over the characteristic length scale and the thickness of the film. The results showed that the characteristic length scale increases with decreasing spin speed and with increasing HPC ratio. The thickness of the spin-coated film decreases with increasing spin speed. It was found that the relation between film thickness and spin speed followed the Meyerhofer equation with an exponent close to 0.5. Furthermore, good correlations between thickness and spin speed were found for the compositions 22 wt% HPC, 30 wt% HPC and 45 wt% HPC. These findings give a good basis for understanding the mechanisms responsible for the morphology development and increase the possibilities to tailor thin EC/HPC film structures.
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| 8. |
- Carmona, Pierre, 1995, et al.
(author)
-
Structure formation and coarsening kinetics of phase-separated spin-coated ethylcellulose/hydroxypropylcellulose films
- 2022
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In: Soft Matter. - : Royal Society of Chemistry. - 1744-683X .- 1744-6848. ; 18:16, s. 3206-3217
-
Journal article (peer-reviewed)abstract
- Porous phase-separated ethylcellulose/hydroxypropylcellulose (EC/HPC) films are used to control drug transport from pharmaceutical pellets. The drug transport rate is determined by the structure of the porous films that are formed as water-soluble HPC leaches out. However, a detailed understanding of the evolution of the phase-separated structure in the films is lacking. In this work, we have investigated EC/HPC films produced by spin-coating, mimicking the industrial fluidized bed spraying. The aim was to investigate film structure evolution and coarsening kinetics during solvent evaporation. The structure evolution was characterized using confocal laser scanning microscopy and image analysis. The effect of the EC:HPC ratio (15 to 85 wt% HPC) on the structure evolution was determined. Bicontinuous structures were found for 30 to 40 wt% HPC. The growth of the characteristic length scale followed a power law, L(t) ∼ t(n), with n ∼ 1 for bicontinuous structures, and n ∼ 0.45-0.75 for discontinuous structures. The characteristic length scale after kinetic trapping ranged between 3.0 and 6.0 μm for bicontinuous and between 0.6 and 1.6 μm for discontinuous structures. Two main coarsening mechanisms could be identified: interfacial tension-driven hydrodynamic growth for bicontinuous structures and diffusion-driven coalescence for discontinuous structures. The 2D in-plane interface curvature analysis showed that the mean curvature decreased as a function of time for bicontinuous structures, confirming that interfacial tension is driving the growth. The findings of this work provide a good understanding of the mechanisms responsible for morphology development and open for further tailoring of thin EC/HPC film structures for controlled drug release. © 2022 The Royal Society of Chemistry
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| 9. |
- Comas, Carles, et al.
(author)
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A third order point process characteristic for multi-type point processes
- 2010
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In: Statistica Neerlandica. - : Wiley. - 0039-0402 .- 1467-9574. ; 64:1, s. 19-44
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Journal article (peer-reviewed)abstract
- The description and analysis of spatial point patterns have mainly been based on first- and second-order characteristics. However, and especially when analyzing complex and multivariate point patterns, the use of higher-order characteristics would be more informative. In this paper, we introduce a third-order characteristic for multi-type point processes, which is based on the number of r-close triples of points, where the three points are of three different types (species). This characteristic is useful, when the second-order characteristics indicate that the three point patterns are pairwise uncorrelated but there is some relationship between triples of points. Furthermore, we conjecture that the new statistic can be used to test independence between the three point processes.
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| 10. |
- Cronie, Ottmar, 1979, et al.
(author)
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Some edge correction methods for marked spatio-temporal point process models
- 2011
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In: Computational Statistics & Data Analysis. - : Elsevier BV. - 0167-9473 .- 1872-7352. ; 55:7, s. 2209-2220
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Journal article (peer-reviewed)abstract
- Three edge correction methods for (marked) spatio-temporal point processes are proposed. They are all based on the idea of placing an approximated expected behaviour of the process at hand (simulated realisations) outside the study region which interacts with the data during the estimation. These methods are applied to the so-called growth-interaction model. The specific choices of growth function and interaction function made are purely motivated by the forestry applications considered. The parameters of the growth and interaction functions, i.e. the parameters related to the development of the marks, are estimated using the least-squares approach together with the proposed edge corrections. Finally, the edge corrected estimation methods are applied to a data set of Swedish Scots pine.
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