| 1. |
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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 4. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 5. |
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| 6. |
- Bahaloo, Hassan, 1983-, et al.
(författare)
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On the failure initiation in the proximal human femur under simulated sideways fall
- 2018
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Ingår i: Annals of Biomedical Engineering. - : Springer. - 0090-6964 .- 1573-9686. ; 46, s. 270-283
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Tidskriftsartikel (refereegranskat)abstract
- The limitations of areal bone mineral density measurements for identifying at-risk individuals have led to the development of alternative screening methods for hip fracture risk including the use of geometrical measurements from the proximal femur and subject specific finite element analysis (FEA) for predicting femoral strength, based on quantitative CT data (qCT). However, these methods need more development to gain widespread clinical applications. This study had three aims: To investigate whether proximal femur geometrical parameters correlate with obtained femur peak force during the impact testing; to examine whether or not failure of the proximal femur initiates in the cancellous (trabecular) bone; and finally, to examine whether or not surface fracture initiates in the places where holes perforate the cortex of the proximal femur. We found that cortical thickness around the trochanteric-fossa is significantly correlated to the peak force obtained from simulated sideways falling (R 2 = 0.69) more so than femoral neck cortical thickness (R 2 = 0.15). Dynamic macro level FE simulations predicted that fracture generally initiates in the cancellous bone compartments. Moreover, our micro level FEA results indicated that surface holes may be involved in primary failure events.
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| 7. |
- Binder, Zev A., et al.
(författare)
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Epidermal Growth Factor Receptor Extracellular Domain Mutations in Glioblastoma Present Opportunities for Clinical Imaging and Therapeutic Development
- 2018
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 34:1, s. 163-177
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Tidskriftsartikel (refereegranskat)abstract
- We explored the clinical and pathological impact of epidermal growth factor receptor (EGFR) extracellular domain missense mutations. Retrospective assessment of 260 de novo glioblastoma patients revealed a significant reduction in overall survival of patients having tumors with EGFR mutations at alanine 289 (EGFR(A289D/T/V)). Quantitative multi-parametric magnetic resonance imaging analyses indicated increased tumor invasion for EGFR(A289D/T/V) mutants, corroborated in mice bearing intracranial tumors expressing EGFR(A289V) and dependent on ERK-mediated expression of matrix metalloproteinase-1. EGFR(A289V) tumor growth was attenuated with an antibody against a cryptic epitope, based on in silico simulation. The findings of this study indicate a highly invasive phenotype associated with the EGFR(A289V) mutation in glioblastoma, postulating EGFR(A289V) as a molecular marker for responsiveness to therapy with EGFR-targeting antibodies.
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| 8. |
- Braesch-Andersen, Anna, et al.
(författare)
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Application of phase-field fracture theories and digital volume correlation to synchrotron X-ray monitored fractures in human trabecular bone : A case study
- 2022
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier. - 1751-6161 .- 1878-0180. ; 135
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Tidskriftsartikel (refereegranskat)abstract
- Fracture processes of trabecular bone have been studied using various approaches over the years. However, reliable methods to analyse fracture at the single trabecula level are limited. In this study, a digital volume correlation (DVC) and a phase-field fracture model are applied and contrasted for human trabecular bone to analyse its failure under global compression at high resolution.A human trabecular bone sample was fractured in situ under synchrotron-based X-ray micro computed to-mography (CT). Reconstructed CT data was then used in DVC algorithms to obtain high-resolution displacement fields in the bone at different load steps. A high-resolution specimen-specific structural mesh was discretized from the CT data and used for the phase-field simulation of the fracturing bone.The DVC analysis showed opening mode cracks as well as shear mode cracks. Strains in cracked regions were analysed. The load distribution in the trabecular structure resulted in two completely separated fracture regions in the sample body. A phenomenon that was also captured in the phase-field model. The results encourage us to believe improvements in boundary conditions and material models are worthwhile pursuing. Findings in this study support further development of a phase-field method to analyse fracture in samples with complex morphology, such as trabecular bone, and the capacity of DVC to quantify strains and slowly growing stable fractures during step-wise loading of trabecular bone.
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| 9. |
- Carlsson, Jenny, et al.
(författare)
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Fracture in porous bone analysed with a numerical phase-field dynamical model
- 2023
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier. - 1751-6161 .- 1878-0180. ; 139
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Tidskriftsartikel (refereegranskat)abstract
- A dynamic phase-field fracture finite element model is applied to discretized high-resolution three-dimensional computed tomography images of human trabecular bone to analyse rapid bone fracture. The model is contrasted to quasi-static experimental results and a quasi-static phase-field finite element model. The experiment revealed complex stepwise crack evolution with multiple crack fronts, and crack arrests, as the global tensile displacement load was incrementally increased. The quasi-static phase-field fracture model captures the fractures in the experiment reasonably well, and the dynamic model converges towards the quasi-static model when mechanically loaded at low rates. At higher load rates, i.e., at larger impulses, inertia effects significantly contribute to an increased initial global stiffness, higher peak forces and a larger number of cracks spread over a larger volume. Since the fracture process clearly is different at large impulses compared to small impulses, it is concluded that dynamic fracture models are necessary when simulating rapid bone fracture.
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| 10. |
- Danaei, Goodarz, et al.
(författare)
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Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants
- 2015
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Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595 .- 2213-8587. ; 3:8, s. 624-637
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Tidskriftsartikel (refereegranskat)abstract
- Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
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| 11. |
- Du, Xiaoyu, et al.
(författare)
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Fabrication and characterization of sodium alginate-silicon nitride-PVA composite biomaterials with damping properties
- 2024
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier. - 1751-6161 .- 1878-0180. ; 155
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Tidskriftsartikel (refereegranskat)abstract
- Silicon nitride is utilized clinically as a bioceramic for spinal fusion cages, owing to its high strength, osteoconductivity, and antibacterial effects. Nevertheless, silicon nitride exhibits suboptimal damping properties, a critical factor in mitigating traumatic bone injuries and fractures. In fact, there is a scarcity of spinal implants that simultaneously demonstrate proficient damping performance and support osteogenesis. In our study, we fabricated a novel sodium alginate-silicon nitride/poly(vinyl alcohol) (SA-SiN/PVA) composite scaffold, enabling enhanced energy absorption and rapid elastic recovery under quasi-static and impact loading scenarios. Furthermore, the study demonstrated that the incorporation of physical and chemical cross-linking significantly improved stiffness and recoverable energy dissipation. Concerning the interaction between cells and materials, our findings suggest that the addition of silicon nitride stimulated osteogenic differentiation while inhibiting Staphylococcus aureus growth. Collectively, the amalgamation of ceramics and tough hydrogels facilitates the development of advanced composites for spinal implants, manifesting superior damping, osteogenic potential, and antibacterial properties. This approach holds broader implications for applications in bone tissue engineering.
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| 12. |
- Du, Xiaoyu, et al.
(författare)
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The porous cantilever beam as a model for spinal implants : Experimental, analytical and finite element analysis of dynamic properties
- 2023
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Ingår i: Mathematical Biosciences and Engineering. - : American Institute of Mathematical Sciences. - 1547-1063 .- 1551-0018. ; 20:4, s. 6273-6293
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Tidskriftsartikel (refereegranskat)abstract
- Investigation of the dynamic properties of implants is essential to ensure safety and compatibility with the host's natural spinal tissue. This paper presents a simplified model of a cantilever beam to investigate the effects of holes/pores on the structures. Free vibration test is one of the most effective methods to measure the dynamic response of a cantilever beam, such as natural frequency and damping ratio. In this study, the natural frequencies of cantilever beams made of polycarbonate (PC) containing various circular open holes were investigated numerically, analytically, and experimentally. The experimental data confirmed the accuracy of the natural frequencies of the cantilever beam with open holes calculated by finite element and analytical models. In addition, two finite element simulation methods, the dynamic explicit and modal dynamic methods, were applied to determine the damping ratios of cantilever beams with open holes. Finite element analysis accurately simulated the damped vibration behavior of cantilever beams with open holes when known material damping properties were applied. The damping behavior of cantilever beams with random pores was simulated, highlighting a completely different relationship between porosity, natural frequency and damping response. The latter highlights the potential of finite element methods to analyze the dynamic response of arbitrary and complex structures, towards improved implant design.
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| 13. |
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| 14. |
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| 15. |
- Grassi, Lorenzo, et al.
(författare)
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Validation of 3d finite element models from simulated Dxa images for Biofidelic simulations of sideways fall impact to the hip
- 2020
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 142
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Tidskriftsartikel (refereegranskat)abstract
- Computed tomography (CT)-derived finite element (FE) models have been proposed as a tool to improve the current clinical assessment of osteoporosis and personalized hip fracture risk by providing an accurate estimate of femoral strength. However, this solution has two main drawbacks, namely: (i) 3D CT images are needed, whereas 2D dual-energy x-ray absorptiometry (DXA) images are more generally available, and (ii) quasi-static femoral strength is predicted as a surrogate for fracture risk, instead of predicting whether a fall would result in a fracture or not. The aim of this study was to combine a biofidelic fall simulation technique, based on 3D computed tomography (CT) data with an algorithm that reconstructs 3D femoral shape and BMD distribution from a 2D DXA image. This approach was evaluated on 11 pelvis-femur constructs for which CT scans, ex vivo sideways fall impact experiments and CT-derived biofidelic FE models were available. Simulated DXA images were used to reconstruct the 3D shape and bone mineral density (BMD) distribution of the left femurs by registering a projection of a statistical shape and appearance model with a genetic optimization algorithm. The 2D-to-3D reconstructed femurs were meshed, and the resulting FE models inserted into a biofidelic FE modeling pipeline for simulating a sideways fall. The median 2D-to-3D reconstruction error was 1.02 mm for the shape and 0.06 g/cm3 for BMD for the 11 specimens. FE models derived from simulated DXAs predicted the outcome of the falls in terms of fracture versus non-fracture with the same accuracy as the CT-derived FE models. This study represents a milestone towards improved assessment of hip fracture risk based on widely available clinical DXA images.
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| 16. |
- Ho, Phay J., et al.
(författare)
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The role of transient resonances for ultra-fast imaging of single sucrose nanoclusters
- 2020
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Intense x-ray free-electron laser (XFEL) pulses hold great promise for imaging function in nanoscale and biological systems with atomic resolution. So far, however, the spatial resolution obtained from single shot experiments lags averaging static experiments. Here we report on a combined computational and experimental study about ultrafast diffractive imaging of sucrose clusters which are benchmark organic samples. Our theoretical model matches the experimental data from the water window to the keV x-ray regime. The large-scale dynamic scattering calculations reveal that transient phenomena driven by non-linear x-ray interaction are decisive for ultrafast imaging applications. Our study illuminates the complex interplay of the imaging process with the rapidly changing transient electronic structures in XFEL experiments and shows how computational models allow optimization of the parameters for ultrafast imaging experiments. X-ray free electron lasers provide high photon flux to explore single particle diffraction imaging of biological samples. Here the authors present dynamic electronic structure calculations and benchmark them to single-particle XFEL diffraction data of sucrose clusters to predict optimal single-shot imaging conditions.
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| 17. |
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| 18. |
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| 19. |
- Koh, Ilsoo, et al.
(författare)
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Ceramic cement as a potential stand-alone treatment for bone fractures: an in vitro study of ceramic-bone composites
- 2016
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161 .- 1878-0180. ; 61, s. 519-529
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Tidskriftsartikel (refereegranskat)abstract
- Background: A vertebral burst fracture (VBF) treated with vertebroplasty using a ceramic cement consists of four regions; native bone fragments, native ceramic cement, ceramic cement-trabecular bone (ceramic-bone) composite and ceramic-bone interface. Although the mechanical properties of native bone and native ceramic cements have been well investigated, the mechanical properties of ceramic-bone composite and ceramic-bone interface remain unknown. Therefore, the aim of this study was to determine the mechanical properties of ceramic-bone composites and ceramic-bone interfaces. Two types of ceramic cement, calcium aluminate (CAC) with (w/F) and without (wo/F) fiber reinforcement, were investigated. Methods: Ceramic-bone composite (Full, wo/F and w/F) and ceramic-bone interface (Fract, wo/F and w/F) groups were tested to determine their compressive and tensile properties. While a continuous bone cylinder was used for samples in the Full groups, each bone cylinder for the samples in the Fract groups contained a 3 mm geometrical discontinuity to mimic the fracture gaps in VBFs. Two Cement groups (wo/F and w/F) and a Bone group were included in the study as controls. Micro-CT images were used to determine the bone morphological parameters, as potential predictors of the mechanical properties of Full and Fract groups. Results: The compressive strengths of Full and Fract groups were substantially lower than native CAC, but higher than bone. The tensile strength of the Full group was equal to bone, while the tensile strength of the Fract group was equivalent to CAC. Variable relationships between the bone morphological parameters and mechanical properties of Full and Fract groups were observed. Fiber reinforcement at an injectable level had a minimal influence on the mechanical properties. Conclusions: CAC augmentation does not provide adequate stabilization of bone fragments. The interface between bone and cement represents a weak point. The effect of cement augmentation cannot be predicted by bone morphological properties.
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| 20. |
- Koh, Ilsoo, et al.
(författare)
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The compressive modulus and strength of saturated calcium sulphate dihydrate cements : Implications for testing standards
- 2014
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161 .- 1878-0180. ; 34, s. 187-198
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Tidskriftsartikel (refereegranskat)abstract
- Calcium sulphate-based bone cement is a bone filler with proven biological advantages including biodegradability, biocompatibility and osteoconductivity. Mechanical properties of such brittle ceramic cements are frequently determined using the testing standard designed for ductile acrylic cements. The aims of the study were (1) to validate the suitability of this common testing protocol using saturated calcium sulphate dihydrate (CSD), and (2) to compare the strength and effective modulus of non-saturated and saturated CSD, in order to determine the changes in the mechanical behavior of CSD upon saturation. Unconfined compression tests to failure were performed on 190 cylind- rical CSD samples. The samples were divided into four groups having different saturation levels (saturated, non-saturated) and end conditions (capped and non-capped). Two effective moduli were calculated per sample, based on the deformations measured using the machine platens and a sample-mounted extensometer. The effective moduli of non-saturated groups were found to be independent of the end conditions. The saturated and capped group showed no difference in the effective moduli derived from different measurement methods, while the saturated and non-capped group showed a significant difference between the machine platen- and extensometer-derived moduli. Strength and modulus values were significantly lower for saturated samples. It was assumed that the existence of water in saturated CSD alters the mechanical response of the material due to the changes in chemical and physical behaviors. These factors are considered to play important roles to decrease the shear strength of CSD. It was proposed that the reduction in CSD shear strength evokes local deformation at the platen–sample boundary, affecting the strength and effective moduli derived from the experiments. The results of this study highlighted the importance of appropriate and consistent testing methods when determining the mechanical properties of saturated ceramic cements.
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| 21. |
- Koh, Ilsoo, et al.
(författare)
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The effect of water on the mechanical properties of soluble and insoluble ceramic cements
- 2015
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier. - 1751-6161 .- 1878-0180. ; 51, s. 50-60
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Tidskriftsartikel (refereegranskat)abstract
- Ceramic cements are good candidates for the stabilization of fractured bone due to their potential ease of application and biological advantages. New formulations of ceramic cements have been tested for their mechanical properties, including strength, stiffness, toughness and durability. The changes in the mechanical properties of a soluble cement (calcium sulfate) upon water-saturation (saturation) was reported in our previous study, highlighting the need to test ceramic cements using saturated samples. It is not clear if the changes in the mechanical properties of ceramic cements are exclusive to soluble cements. Therefore the aim of the present study was to observe the changes in the mechanical properties of soluble and insoluble ceramic cements upon saturation. A cement with high solubility (calcium sulfate dihydrate, CSD) and a cement with low solubility (dicalcium phosphate dihydrate, DCPD) were tested. Three-point bending tests were performed on four different groups of: saturated CSD, non-saturated CSD, saturated DCPD, and non-saturated DCPD samples. X-ray diffraction analysis and scanning electron microscopy were also performed on a sample from each group. Flexural strength, effective flexural modulus and flexural strain at maximum stress, lattice volume, and crystal sizes and shape were compared, independently, between saturated and non-saturated groups of CSD and DCPD. Although material dissolution did not occur in all cases, all calculated mechanical properties decreased significantly in both CSD and DCPD upon saturation. The results indicate that the reductions in the mechanical properties of saturated ceramic cements are not dependent on the solubility of a ceramic cement. The outcome raised the importance of testing any implantable ceramic cements in saturated condition to estimate its in vivo mechanical properties. (C) 2015 Elsevier Ltd. All rights reserved.
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| 22. |
- Lepuschitz, Sarah, et al.
(författare)
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Multicenter Study of Cronobacter sakazakii Infections in Humans, Europe, 2017
- 2019
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Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 25:3, s. 515-522
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Tidskriftsartikel (refereegranskat)abstract
- Cronobacter sakazakii has been documented as a cause of life-threating infections, predominantly in neonates. We conducted a multicenter study to assess the occurrence of C. sakazakii across Europe and the extent of clonality for outbreak detection. National coordinators representing 24 countries in Europe were requested to submit all human C. sakazakii isolates collected during 2017 to a study center in Austria. Testing at the center included species identification by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, subtyping by whole-genome sequencing (WGS), and determination of antimicrobial resistance. Eleven countries sent 77 isolates, including 36 isolates from 2017 and 41 historical isolates. Fifty-nine isolates were confirmed as C. sakazakii by WGS, highlighting the challenge of correctly identifying Cronobacter spp. WGS-based typing revealed high strain diversity, indicating absence of multi-national outbreaks in 2017, but identified 4 previously unpublished historical outbreaks. WGS is the recommended method for accurate identification, typing, and detection of this pathogen.
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| 23. |
- Lewin, Susanne, et al.
(författare)
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Additively manufactured mesh-type titanium structures for cranial implants : E-PBF vs. L-PBF
- 2021
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Ingår i: Materials & design. - : Elsevier. - 0264-1275 .- 1873-4197. ; 197
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Tidskriftsartikel (refereegranskat)abstract
- A patient-specific titanium-reinforced calcium phosphate (CaP–Ti) cranial implant has recently shown promising clinical results. Currently, its mesh-type titanium structure is additively manufactured using laser beam powder bed fusion (L-PBF). Nevertheless, an electron-beam (E-PBF) process could potentially be more time efficient. This study aimed to compare the geometrical accuracy and mechanical response of thin titanium structures manufactured by L-PBF (HIPed) and E-PBF (as-printed). Tensile test (ø = 1.2 mm) and implant specimens were manufactured. Measurements by μCT revealed a deviation in cross-sectional area as compared to the designed geometry: 13–35% for E-PBF and below 2% for L-PBF. A superior mechanical strength was obtained for the L-PBF specimens, both in the tensile test and the implant compression tests. The global peak load in the implant test was 457 ± 9 N and 846 ± 40 N for E-PBF and L-PBF, respectively. Numerical simulations demonstrated that geometrical deviation was the main factor in implant performance and enabled quantification of this effect: 34–39% reduction in initial peak force based on geometry, and only 11–16% reduction based on the material input. In summary, the study reveals an uncertainty in accuracy when structures of sizes relevant to mesh-type cranial implants are printed by the E-PBF method.
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| 24. |
- Lewin, Susanne, et al.
(författare)
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Implicit and explicit finite element models predict the mechanical response of calcium phosphate-titanium cranial implants
- 2020
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier. - 1751-6161 .- 1878-0180. ; 112
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Tidskriftsartikel (refereegranskat)abstract
- The structural integrity of cranial implants is of great clinical importance, as they aim to provide cerebral protection after neurosurgery or trauma. With the increased use of patient-specific implants, the mechanical response of each implant cannot be characterized experimentally in a practical way. However, computational models provide an excellent possibility for efficiently predicting the mechanical response of patient-specific implants. This study developed finite element models (FEMs) of titanium-reinforced calcium phosphate (CaP-Ti) implants. The models were validated with previously obtained experimental data for two different CaP-Ti implant designs (D1 and D2), in which generically shaped implant specimens were loaded in compression at either quasi-static (1 mm/min) or impact (5 kg, 1.52 m/s) loading rates. The FEMs showed agreement with experimental data in the force-displacement response for both implant designs.The implicit FEMs predicted the peak load with an underestimation for D1 (9%) and an overestimation for D2 (11%). Furthermore, the shape of the force-displacement curves were well predicted. In the explicit FEMs, the first part of the force-displacement response showed 5% difference for D1 and 2% difference for D2, with respect to the experimentally derived peak loads. The explicit FEMs efficiently predicted the maximum dis-placements with 1% and 4% difference for D1 and D2, respectively. Compared to the CaP-Ti implant, an average parietal cranial bone FEM showed a stiffer response, greater energy absorption and less deformation under the same impact conditions.The framework developed for modelling the CaP-Ti implants has a potential for modelling CaP materials in other composite implants in future studies since it only used literature based input and matched boundary conditions. Furthermore, the developed FEMs make an important contribution to future evaluations of patient specific CaP-Ti cranial implant designs in various loading scenarios.
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| 25. |
- Lewin, Susanne, et al.
(författare)
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Mechanical behaviour of composite calcium phosphate-titanium cranial implants : Effects of loading rate and design
- 2020
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161 .- 1878-0180. ; 104
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Tidskriftsartikel (refereegranskat)abstract
- Cranial implants are used to repair bone defects following neurosurgery or trauma. At present, there is a lack of data on their mechanical response, particularly in impact loading. The aim of the present study was to assess the mechanical response of a recently developed composite calcium phosphate-titanium (CaP-Ti) implant at quasi-static and impact loading rates. Two different designs were tested, referred to as Design 1 (D1) and Design 2 (D2). The titanium structures in the implant specimens were additively manufactured by a powder-bed fusion process and subsequently embedded in a self-setting CaP material. D1 was conceptually representative of the clinically used implants. In D2, the titanium structure was simplified in terms of geometry in order to facilitate the manufacturing. The mechanical response of the implants was evaluated in quasi-static compression, and in impact using a drop-tower. Similar peak loads were obtained for the two designs, at the two loading rates: 808 ± 29 N and 852 ± 34 for D1, and 840 ± 40 N and 814 ± 13 for D2. A strain rate dependency was demonstrated for both designs, with a higher stiffness in the impact test. Furthermore, the titanium in the implant fractured in the quasi-static test (to failure) but not in the impact test (to 5.75 J) for D1. For D2, the displacement at peak load was significantly lower in the impact test than in the quasi-static test. The main difference between the designs was seen in the quasi-static test results where the deformation zones, i.e. notches in the titanium structure between the CaP tiles, in D1 likely resulted in a localization of the deformation, compared to in D2 (which did not have deformation zones). In the impact test, the only significant difference between the designs was a higher maximum displacement of D2 than of D1. In comparison with other reported mechanical tests on osteoconductive ceramic-based cranial implants, the CaP-Ti implant demonstrates the highest reported strength in quasi-static compression. In conclusion, the titanium structure seems to make the CaP-Ti implant capable of cerebral protection in impact situations like the one tested in this study.
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| 26. |
- Lindblad-Toh, Kerstin, et al.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 27. |
- López, Alejandro, et al.
(författare)
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Compressive mechanical properties and cytocompatibility of bone-compliant, linoleic acid-modified bone cement in a bovine model
- 2014
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161 .- 1878-0180. ; 32, s. 245-256
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Tidskriftsartikel (refereegranskat)abstract
- Adjacent vertebral fractures are a common complication experienced by osteoporosis patients shortly after vertebroplasty. Whether these fractures are due to the bone cement properties, the cement filling characteristics or to the natural course of the disease is still unclear. However, some data suggests that such fractures might occur because of an imbalance in the load distribution due to a mismatch between the elastic modulus (E) of the bone-cement composite, and that of the vertebral cancellous bone. In this study, the properties of bone-compliant linoleic acid-modified bone cements were assessed using a bovine vertebroplasty model. Two groups of specimens (cement-only and bone-cement composites), and four subgroups comprising bone cements with elastic moduli in the range of 870-3500 MPa were tested to failure in uniaxial compression. In addition, monomer release as well as time and concentration-dependent cytocompatibility was assessed through the cement extracts using a Saos-2 cell model. Composites augmented with bone-compliant cements exhibited a reduction in E despite their relatively high bone volume fraction (BVF). Moreover, a significant positive correlation between the BVF and the E for the composites augmented with 870 MPa modulus cements was found. This was attributed to the increased relative contribution of the bone to the mechanical properties of the composites with a decrease in E of the bone cement. The use of linoleic acid reduced monomer conversion resulting in six times more monomer released after 24 h. However, the cytocompatibility of the bone-compliant cements was comparable to that of the unmodified cements after the extracts were diluted four times. This study represents an important step towards introducing viable bone-compliant bone cements into vertebroplasty practice.
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| 28. |
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| 29. |
- Morin, Phillip A., et al.
(författare)
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Geographic and temporal dynamics of a global radiation and diversification in the killer whale
- 2015
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 24:15, s. 3964-3979
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Tidskriftsartikel (refereegranskat)abstract
- Global climate change during the Late Pleistocene periodically encroached and then released habitat during the glacial cycles, causing range expansions and contractions in some species. These dynamics have played a major role in geographic radiations, diversification and speciation. We investigate these dynamics in the most widely distributed of marine mammals, the killer whale (Orcinus orca), using a global data set of over 450 samples. This marine top predator inhabits coastal and pelagic ecosystems ranging from the ice edge to the tropics, often exhibiting ecological, behavioural and morphological variation suggestive of local adaptation accompanied by reproductive isolation. Results suggest a rapid global radiation occurred over the last 350000years. Based on habitat models, we estimated there was only a 15% global contraction of core suitable habitat during the last glacial maximum, and the resources appeared to sustain a constant global effective female population size throughout the Late Pleistocene. Reconstruction of the ancestral phylogeography highlighted the high mobility of this species, identifying 22 strongly supported long-range dispersal events including interoceanic and interhemispheric movement. Despite this propensity for geographic dispersal, the increased sampling of this study uncovered very few potential examples of ancestral dispersal among ecotypes. Concordance of nuclear and mitochondrial data further confirms genetic cohesiveness, with little or no current gene flow among sympatric ecotypes. Taken as a whole, our data suggest that the glacial cycles influenced local populations in different ways, with no clear global pattern, but with secondary contact among lineages following long-range dispersal as a potential mechanism driving ecological diversification.
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| 30. |
- Newell, Felicity, et al.
(författare)
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Whole-genome landscape of mucosal melanoma reveals diverse drivers and therapeutic targets
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge of key drivers and therapeutic targets in mucosal melanoma is limited due to the paucity of comprehensive mutation data on this rare tumor type. To better understand the genomic landscape of mucosal melanoma, here we describe whole genome sequencing analysis of 67 tumors and validation of driver gene mutations by exome sequencing of 45 tumors. Tumors have a low point mutation burden and high numbers of structural variants, including recurrent structural rearrangements targeting TERT, CDK4 and MDM2. Significantly mutated genes are NRAS, BRAF, NF1, KIT, SF3B1, TP53, SPRED1, ATRX, HLA-A and CHD8. SF3B1 mutations occur more commonly in female genital and anorectal melanomas and CTNNB1 mutations implicate a role for WNT signaling defects in the genesis of some mucosal melanomas. TERT aberrations and ATRX mutations are associated with alterations in telomere length. Mutation profiles of the majority of mucosal melanomas suggest potential susceptibility to CDK4/6 and/or MEK inhibitors.
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| 31. |
- Persson, Johan, et al.
(författare)
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Stiffness and strength of cranioplastic implant systems in comparison to cranial bone
- 2018
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Ingår i: Journal of Cranio-Maxillofacial Surgery. - : Elsevier BV. - 1010-5182 .- 1878-4119. ; 46:3, s. 418-423
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of this study was to evaluate skull replacement options after decompressive craniectomy by systematically investigating which combination of geometrical properties and material selection would result in a mechanical response comparable in stiffness to that of native skull bone and a strength as high or higher than the same. Materials and methods: The study was conducted using a Finite Element Model of the top part of a human skull. Native skull bone, autografts and commercial implants made of PEEK, solid titanium, two titanium meshes and a titanium-ceramic composite were modeled under a set load to evaluate deformation and maximum stress. Results: The computational result showed a large variation of the strength and effective stiffness of the autografts and implants. The stiffness of native bone varied by a factor of 20 and the strength by a factor of eight. The implants span the entire span of the native skull, both in stiffness and strength. Conclusion: All the investigated implant materials had a potential for having the same effective stiffness as the native skull bone. All the materials also had the potential to be as strong as the native bone. To match inherent properties, the best choice of material and thickness is thus patient specific, depending on the quality of the patient's native bone.
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| 32. |
- Röthlin, Philipp, et al.
(författare)
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Self-Compassion in Competitive Sport: The «Why», «How», «When» and «For Whom»
- 2022
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Ingår i: Proceedings from the 16th European Congress of Sport & Exercise Psychology (FEPSAC). - : FEPSAC. ; , s. 597-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The integration of self-compassion is becoming more common in sport; however, there are many considerations for how to effectively integrate self-compassion in differing sport contexts. The goals for participants in this applied workshop are to 1) to learn about self-compassion (Neff, 2003; Gilbert, 2009) and key research findings relevant to competitive sport (Mosewich et al., 2019), 2) experience a range of self-compassion exercises applicable in sport, and 3) reflect and critically discuss how to effectively deliver self-compassion exercises and embed self-compassion strategies in applied sport psychology settings. In doing so, we place a strong focus on considering important factors such as context and population. To achieve these goals, an international collaboration of experts will lead and demonstrate a variety of evidence-based self-compassion exercises with participants (e.g., imagery exercises, cognitive behavioral exercises, psychoeducation; e.g., Germer & Neff, 2019; Van den Brink & Koster, 2015). Participants will then (a) discuss in small groups how to best integrate the exercises into their specific sport context, (b) share the results of the group discussion within a plenary session, and (c) provide and receive feedback on the presented ideas from the other participants and the international experts. Overall, the workshop will emphasize how to integrate self-compassion into diverse sport contexts with a range of sport participants (e.g., athletes, coaches, officials). Throughout, reference will be made to current research findings as well as exemplary cases from the experience of the international experts. Participants will receive a compilation of all exercises and worksheets.
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| 33. |
- Widmer Soyka, Rene P., et al.
(författare)
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Numerical description and experimental validation of a rheology model for non-Newtonian fluid flow in cancellous bone
- 2013
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161 .- 1878-0180. ; 27, s. 43-53
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Tidskriftsartikel (refereegranskat)abstract
- Fluids present or used in biology, medicine and (biomedical) engineering are often significantly non-Newtonian. Furthermore, they are chemically complex and can interact with the porous matrix through which they flow. The porous structures themselves display complex morphological inhomogeneities on a wide range of length scales. In vertebroplasty, a shear-thinning fluid, e.g. poly(methyl methacrylate) (PMMA), is injected into the cavities of vertebral trabecular bone for the stabilization of fractures and metastatic lesions. The main objective of this study was therefore to provide a protocol for numerically investigating the rheological properties of PMMA-based bone cements to predict its spreading behavior while flowing through vertebral trabecular bone. A numerical upscaling scheme based on a dimensionless formulation of the Navier-Stokes equation is proposed in order to relate the pore-scale rheological properties of the PMMA that were experimentally estimated using a plate rheometer, to the continuum-scale. On the pore length scale, a viscosity change on the order of one magnitude was observed whilst, the shear-thinning properties caused a viscosity change on the order of only 10% on the continuum length scale and in a flow regime that is relevant for vertebroplasty. An experimental validation, performed on human cadaveric vertebrae (n=9), showed a significant improvement of the cement spreading prediction accuracy with a non-Newtonian formulation. A root mean square cement surface prediction error of 1.53 mm (assuming a Newtonian fluid) and 1.37 mm (assuming a shear-thinning fluid) was found. Our findings highlight the importance of incorporating the non-Newtonian fluids properties in computational models of porous media at the appropriate length scale.
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| 34. |
- Wu, Dan, 1990-, et al.
(författare)
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A combined experimental and numerical method to estimate the elastic modulus of single trabeculae
- 2022
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier. - 1751-6161 .- 1878-0180. ; 125
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Tidskriftsartikel (refereegranskat)abstract
- The elastic modulus at the single trabecular level is an important parameter for the understanding of the mechanical behavior of trabecular bone. Current methods are commonly limited by the irregular trabecular shape and the accuracy of displacement measurement. The aim of this study was to propose a method to estimate the trabecular modulus overcoming some of these limitations. For high-precision displacement measurements, insitu compression within a synchrotron radiation based X-ray tomograph was used. Trabecular displacements were subsequently estimated by a global digital volume correlation algorithm, followed by high-resolution finite element analyses to account for the irregular geometry. The trabecular elastic moduli were then estimated by comparing the loads from the finite element analyses with those of the experiments. With this strategy, the average elastic modulus was estimated to 3.83 +/- 0.54 GPa for three human trabeculae samples. Though limited by the sample size, the demonstrated method shows a potential to estimate the mechanical properties at the single trabecular level.
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| 35. |
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| 36. |
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| 37. |
- Wu, Dan, 1990-, et al.
(författare)
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Young’s modulus of trabecular bone at the tissue level : A review
- 2018
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 78, s. 1-12
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Forskningsöversikt (refereegranskat)abstract
- The tissue-level Young’s modulus of trabecular bone is important for detailed mechanical analysis of bone and bone-implant mechanical interactions. However, the heterogeneity and small size of the trabecular struts complicate an accurate determination. Methods such as micro-mechanical testing of single trabeculae, ultrasonic testing, and nanoindentation have been used to estimate the trabecular Young’s modulus. This review summarizes and classifies the trabecular Young’s moduli reported in the literature. Information on species, anatomic site, and test condition of the samples has also been gathered. Advantages and disadvantages of the different methods together with recent developments are discussed, followed by some suggestions for potential improvement, for future work. In summary, this review provides a thorough introduction to the approaches used for determining trabecular Young’s modulus, highlights important considerations when applying these methods and summarizes the reported Young’s modulus for follow-up studies on trabecular properties.
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| 38. |
- Zhou, Yijun, et al.
(författare)
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A convolutional neural network-based method for the generation of super-resolution 3D models from clinical CT images
- 2024
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Ingår i: Computer Methods and Programs in Biomedicine. - : Elsevier. - 0169-2607 .- 1872-7565. ; 245
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectiveThe accurate evaluation of bone mechanical properties is essential for predicting fracture risk based on clinical computed tomography (CT) images. However, blurring and noise in clinical CT images can compromise the accuracy of these predictions, leading to incorrect diagnoses. Although previous studies have explored enhancing trabecular bone CT images to super-resolution (SR), none of these studies have examined the possibility of using clinical CT images from different instruments, typically of lower resolution, as a basis for analysis. Additionally, previous studies rely on 2D SR images, which may not be sufficient for accurate mechanical property evaluation, due to the complex nature of the 3D trabecular bone structures. The objective of this study was to address these limitations.Methods: A workflow was developed that utilizes convolutional neural networks to generate SR 3D models across different clinical CT instruments. The morphological and finite-element-derived mechanical properties of these SR models were compared with ground truth models obtained from micro-CT scans.Results: A significant improvement in analysis accuracy was demonstrated, where the new SR models increased the accuracy by up to 700 % compared with the low-resolution data, i.e. clinical CT images. Additionally, we found that the mixture of different CT image datasets may improve the SR model performance.Conclusions: SR images, generated by convolutional neural networks, outperformed clinical CT images in the determination of morphological and mechanical properties. The developed workflow could be implemented for fracture risk prediction, potentially leading to improved diagnoses and subsequent clinical decision making.
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| 39. |
- Zhou, Yijun, et al.
(författare)
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A convolutional neural network-based method for the generation of super-resolution 3D models from clinical CT images
- 2024
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Ingår i: Computer Methods and Programs in Biomedicine. - : Elsevier. - 0169-2607 .- 1872-7565. ; 245
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Tidskriftsartikel (refereegranskat)abstract
- Background and ObjectiveThe accurate evaluation of bone mechanical properties is essential for predicting fracture risk based on clinical computed tomography (CT) images. However, blurring and noise in clinical CT images can compromise the accuracy of these predictions, leading to incorrect diagnoses. Although previous studies have explored enhancing trabecular bone CT images to super-resolution (SR), none of these studies have examined the possibility of using clinical CT images from different instruments, typically of lower resolution, as a basis for analysis. Additionally, previous studies rely on 2D SR images, which may not be sufficient for accurate mechanical property evaluation, due to the complex nature of the 3D trabecular bone structures. The objective of this study was to address these limitations.MethodsA workflow was developed that utilizes convolutional neural networks to generate super-resolution 3D models across different clinical CT instruments. The morphological and finite-element-derived mechanical properties of these super-resolution models were compared with ground truth models obtained from micro-CT scans.ResultsA significant improvement in analysis accuracy was demonstrated, where the new SR models increased the accuracy by up to 700% compared with the low-resolution data, i.e. clinical CT images. Additionally, we found that the mixture of different CT image datasets may improve the super-resolution model performance.ConclusionsSuper-resolution images, generated by convolutional neural networks, outperformed clinical CT images in the determination of morphological and mechanical properties. The developed workflow could be implemented for fracture risk prediction, potentially leading to improved diagnoses and subsequent clinical decision making.
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| 40. |
- Zhou, Yijun, 1993-, et al.
(författare)
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Optimization of Primary Screw Stability Using Neural Network-Based Models
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Screw implant stability in bone is crucial to the success of many orthopaedic procedures. However, there is no complete map over the relationship between the main screw design parameters and its primary stability in bone. This study presents a novel approach for optimizing screw design parameters using a combination of numerical pull-out simulations and surrogate modelling based on neural network models. The models, trained with various input parameters including bone morphological parameters and CT images, accurately predicted the results of the simulations. It was also found that the bone volume fraction, trabecular bone orientation, and screw insertion position are the three most critical parameters that can influence the prediction accuracy. A series of subsequent optimization tasks were conducted on 80 distinct trabecular bone samples, with optimized screw designs showing significant improvements in pull-out stiffness and strength (approximately 17 and 15%, respectively). The insights gained from this study could have far-reaching implications for personalized medicine and the development of patient-specific orthopaedic treatments.
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| 41. |
- Zhou, Yijun, 1993-, et al.
(författare)
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Validated, high-resolution, non-linear, explicit finite element models for simulating screw - bone interaction
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background and Objective: Primary stability evaluation of screw implants through pull-out or push-in experiments is commonly used to investigate the mechanism of screw loosening. Numerical models simulating these testing methods could provide an enhanced understanding of the underlying attachment mechanisms as well as save time and cost in the development of new screws. However, previous numerical models have been limited by compromises between modelling the trabecular structure at high resolution versus incorporating sophisticated mechanical properties and boundary conditions, leading to overestimated mechanical performance. The aim of this study was to overcome these limitations.Methods: We developed explicit models incorporating the microstructure of trabecular bone, with frictional contact, and a non-linear material model incorporating damage. One model digitally inserted the screw into the trabecular bone structure using Boolean operations, while another model simulated the screw's rotational insertion. Results: The results showed a strong correlation between numerical and experimental results (R2: 0.54-0.93) for force-displacement response in terms of stiffness and strength. We found that the damage induced by the screw insertion process is an important factor to be considered, as the absence of modelling it led to an overestimated stiffness in previous studies.Conclusions: The study highlights the importance of including frictional contact and also identified screw insertion damage as an important part of the simulating screw-bone interaction. Our findings demonstrate the potential of explicit finite element models for accurately replicating experimental push-in results and optimizing orthopaedic screws.
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| 42. |
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