| 1. |
- Dobbins, Sara E., et al.
(författare)
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Common variation at 10p12.31 near MLLT10 influences meningioma risk
- 2011
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Ingår i: Nature Genetics. - London : Nature America, Inc.. - 1061-4036 .- 1546-1718. ; 43:9, s. 825-827
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 x 10(-14)). This finding advances our understanding of the genetic basis of meningioma development.
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| 2. |
- Enciso-Mora, Victor, et al.
(författare)
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Deciphering the 8q24.21 association for glioma
- 2013
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:11, s. 2293-2302
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Tidskriftsartikel (refereegranskat)abstract
- We have previously identified tagSNPs at 8q24.21 influencing glioma risk. We have sought to fine-map the location of the functional basis of this association using data from four genome-wide association studies, comprising a total of 4147 glioma cases and 7435 controls. To improve marker density across the 700 kb region, we imputed genotypes using 1000 Genomes Project data and high-coverage sequencing data generated on 253 individuals. Analysis revealed an imputed low-frequency SNP rs55705857 (P = 2.24 x 10(-38)) which was sufficient to fully capture the 8q24.21 association. Analysis by glioma subtype showed the association with rs55705857 confined to non-glioblastoma multiforme (non-GBM) tumours (P = 1.07 x 10(-67)). Validation of the non-GBM association was shown in three additional datasets (625 non-GBM cases, 2412 controls; P = 1.41 x 10(-28)). In the pooled analysis, the odds ratio for low-grade glioma associated with rs55705857 was 4.3 (P = 2.31 x 10(-94)). rs55705857 maps to a highly evolutionarily conserved sequence within the long non-coding RNA CCDC26 raising the possibility of direct functionality. These data provide additional insights into the aetiological basis of glioma development.
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| 3. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 4. |
- Ghandour, Salim, et al.
(författare)
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A model for the biomechanical assessment of discoplasty in a laboratory setting
- 2021
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Percutaneous cement discoplasty is a spinal surgical technique which has been rarely tested outside the clinical setting. This study aimed at developing an ovine model framework to allow testing and optimization of discoplasty in a lab-controlled environment.
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| 5. |
- Ghandour, Salim, et al.
(författare)
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An ex-vivo Biomechanical Assessment of Cement Discoplasty
- 2021
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Spinal fusion is the golden standard for treating degenerative disc disease. However, elderly patients with underlying chronic conditions cannot undergo spinal fusion due to healing impairment, risks of infection, and/or even morbidity. Percutaneous Cement Discoplasty (PCD) is a relatively new procedure that involves injecting poly(methyl methacrylate) (PMMA) cement into the disc to reduce pain and attempt to maintain spinal curvature and height. Therefore, this minimally invasive method could be an advantageous option for patients for whom open surgery is deemed too risky [1]. While this technique has already been attempted clinically, to the authors knowledge, only one preliminary study on the biomechanics of PCD is currently available [2]. This study aims to develop a more clinically relevant and repeatable method to study PCD in a lab setting. To this end, ovine spine was tested in three different categories: healthy disc; injured disc; treated disc. A papain enzyme solution [3] was used to create the vacuum phenomena in the sheep spine to represent the injury as observed in a clinical setting. Preliminary compression testing showed promising results with a significant increase in stability of the segments after treatment. Further on, this testing method can be used to test different materials, surgical methods and biomechanical behaviour to further advance PCD.
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| 6. |
- Ghandour, Salim, et al.
(författare)
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An ex-vivo model for the biomechanical assessment of cement discoplasty
- 2022
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media S.A.. - 2296-4185. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Percutaneous Cement Discoplasty (PCD) is a surgical technique developed to relieve pain in patients with advanced degenerative disc disease characterized by a vacuum phenomenon. It has been hypothesized that injecting bone cement into the disc improves the overall stability of the spinal segment. However, there is limited knowledge on the biomechanics of the spine postoperatively and a lack of models to assess the effect of PCD ex-vivo. This study aimed to develop a biomechanical model to study PCD in a repeatable and clinically relevant manner. Eleven ovine functional spinal units were dissected and tested under compression in three conditions: healthy, injured and treated. Injury was induced by a papain buffer and the treatment was conducted using PMMA cement. Each sample was scanned with micro-computed tomography (CT) and segmented for the three conditions. Similar cement volumes (in %) were injected in the ovine samples compared to volumes measured on clinical PCD CT images. Anterior and posterior disc heights decreased on average by 22.5% and 23.9% after injury. After treatment, the anterior and posterior disc height was restored on average to 98.5% and 83.6%, respectively, of their original healthy height. Compression testing showed a similar stiffness behavior between samples in the same group. A decrease of 51.5% in segment stiffness was found after injury, as expected. The following PCD treatment was found to result in a restoration of stiffness—showing only a difference of 5% in comparison to the uninjured state. The developed ex-vivo model gave an adequate representation of the clinical vacuum phenomena in terms of volume, and a repeatable mechanical response between samples. Discoplasty treatment was found to give a restoration in stiffness after injury. The data presented confirm the effectiveness of the PCD procedure in terms of restoration of axial stiffness in the spinal segment. The model can be used in the future to test more complex loading scenarios, novel materials, and different surgical techniques.
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| 7. |
- Grzeszczak, Ana, 1995-, et al.
(författare)
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Mechanical and Structural Evaluation of Synthetic Trabecular Bone Models Printed with Stereolithography
- 2021
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Ingår i: Mechanical and Structural Evaluation of Synthetic Trabecular Bone Models Printed with Stereolithography.
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Konferensbidrag (refereegranskat)abstract
- Mechanical and Structural Evaluation of Synthetic Trabecular Bone Models Printed with StereolithographyA. Grzeszczak1, S. Lewin1, O. Eriksson2, J. Kreuger2, C. Persson11Department of Materials Science and Engineering, Uppsala University, Uppsala, Sweden2Department of Medical Cell Biology, Uppsala University, Uppsala, SwedenINTRODUCTION: Synthetic bone models are needed to train surgeons but also to test and design medical equipment. However, currently available models do not accurately mimic the complex structure of trabecular bone [1]. This study aimed to investigate the suitability of stereolithography (SLA) printing to produce synthetic trabecular bone models.METHODS: The synthetic bone models were printed by SLA using a CAD-model generated from micro-computed tomography (micro-CT) synchrotron images of human trabecular bone [2]. To adjust the printing parameters, the influence of the following variables on the mechanical properties was investigated: printer type, orientation, resolution and UV-curing time. Subsequently, the trabecular CAD-model was printed at the original scale (scale factor 1), and with several enlarging factors. Mechanical properties were evaluated by compression and screw pullout tests, and structure replicability was assessed with micro-CT.RESULTS & DISCUSSION: The elastic modulus of the control group was not statistically different from that of the other batches after the printing parameters configuration, standard parameters were therefore used. The orientation of the samples on the build platform of the printer did not seem to have an influence on the ratio Bone Volume/Total Volume for trabecular samples. For the bone models with scaling factors below 1.8, micro-CT image analysis showed major artefacts due to printing and a low accuracy in trabecular thickness distribution. Analysis of the total printed volume showed a difference to the original model higher than 50% for scale 1.5 and lower than 10% for scales 1.8 and above (Fig. 1). A refined overlap comparison with the original bone model showed that the scale 1.8 exhibited errors higher than 20%, implying printing inaccuracies of the smaller details. The pullout strength obtained for SLA-printed parts was higher than for existing synthetic models (Sawbones™) and cadaveric specimens, but within the same range as FDM-printed parts in poly(lactic acid) [2].CONCLUSIONS: Trabecular bone models with a scale factor of 1.8 or greater could be produced with acceptable accuracy, but models with smaller scale factors were not well printed. Nevertheless, for the same 3D model, a higher resolution was reached by SLA as compared to FDM [2].ACKNOWLEDGEMENTS: The authors are grateful to Adam Engberg at U-PRINT: Uppsala University’s 3D-printing facility at the Disciplinary Domain of Medicine and Pharmacy for support and advice on the printers. This research was funded by Sweden’s Innovation Agency VINNOVA, grant number 2019-00029.REFERENCES: [1] M. Poukalova et al., “Pullout strength of suture anchors: Effect of mechanical properties of trabecular bone,” J. Biomech., vol. 43, no. 6, pp. 1138–1145, Apr. 2010, doi: 10.1016/j.jbiomech.2009.12.007. [2] D. Wu, A. Spanou, A. Diez-Escudero, and C. Persson, “3D-printed PLA/HA composite structures as synthetic trabecular bone: A feasibility study using fused deposition modeling,” J. Mech. Behav. Biomed. Mater., vol. 103, p. 103608, Mar. 2020, doi: 10.1016/j.jmbbm.2019.103608.
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| 8. |
- Grzeszczak, Ana, 1995-, et al.
(författare)
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Stereolithography shows potential in additive manufacturing ofsynthetic trabecular bone structures
- 2021
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Ingår i: Stereolithography shows potential in additive manufacturing ofsynthetic trabecular bone structures.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Title and AuthorsTitle: Stereolithography shows potential in additive manufacturing of synthetic trabecular bone structures.Authors: Ana Grzeszczak, Susanne Lewin, Olle Eriksson, Johan Kreuger, Cecilia Persson IntroductionSynthetic bone models are needed to train surgeons but also to test and design medical devices such as screws for fracture fixation. However, currently available models do not accurately mimic the trabecular bone and its complex structure [1]. This study aimed to investigate if stereolithography (SLA) additive manufacturing could produce synthetic trabecular bone models with high accuracy. Experimental methods The synthetic bone models were printed by SLA (Formlabs Black resin, Form3 printer). The CAD-model had been generated from micro-computed tomography (micro-CT) synchrotron images of human trabecular bone [2]. The model was printed at the original scale (scale factor 1), and with upscaling factors up to 4.3. Structure replicability was assessed with micro-CT, and the mechanical properties were evaluated by compression and screw pullout tests. Dense cylinders of the printed material were also tested in compression for material characterization.Results and discussionThe elastic moduli obtained by compression of dense cylinders were approximately ten times lower than average values for human cortical bone. For the trabecular bone models with scaling factors below 1.8, micro-CT image analysis showed major artefacts due to printing and a low accuracy in trabecular thickness distribution. Analysis of the total printed volume showed a difference to the original model higher than 50% for scale 1.5 (Fig. 1). However, this difference was less than 10% for scales 1.8 and above, although a refined overlap comparison with the original bone model showed that the scale 1.8 exhibited errors higher than 20%, implying printing inaccuracies of the smaller details. The pullout strength of SLA-printed parts was higher than for existing synthetic models (Sawbones™) and cadaveric specimens, but within the same range as FDM-printed parts in poly(lactic acid) [2].ConclusionIn conclusion, trabecular bone models with a scale factor of 1.8 or larger could be printed with acceptable accuracy, but models with smaller scale factors were not well represented. However, for the same 3D model, a higher resolution was achieved by SLA as compared to FDM [2]. AcknowledgementsThe authors are grateful to Adam Engberg at U-PRINT: Uppsala University’s 3D-printing facility at the Disciplinary Domain of Medicine and Pharmacy for support and advice on the printers. This research was funded by Sweden’s Innovation Agency VINNOVA, grant number 2019-00029.References[1] M. Poukalova et al., “Pullout strength of suture anchors: Effect of mechanical properties of trabecular bone,” J. Biomech., vol. 43, no. 6, pp. 1138–1145, Apr. 2010, doi: 10.1016/j.jbiomech.2009.12.007.[2] D. Wu, A. Spanou, A. Diez-Escudero, and C. Persson, “3D-printed PLA/HA composite structures as synthetic trabecular bone: A feasibility study using fused deposition modeling,” J. Mech. Behav. Biomed. Mater., vol. 103, p. 103608, Mar. 2020, doi: 10.1016/j.jmbbm.2019.103608.
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| 9. |
- Grzeszczak, Ana, et al.
(författare)
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The Potential of Stereolithography for 3D Printing of Synthetic Trabecular Bone Structures
- 2021
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Ingår i: Materials. - : MDPI. - 1996-1944. ; 14:13
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Tidskriftsartikel (refereegranskat)abstract
- Synthetic bone models are used to train surgeons as well as to test new medical devices. However, currently available models do not accurately mimic the complex structure of trabecular bone, which can provide erroneous results. This study aimed to investigate the suitability of stereolithography (SLA) to produce synthetic trabecular bone. Samples were printed based on synchrotron micro-computed tomography (micro-CT) images of human bone, with scaling factors from 1 to 4.3. Structure replicability was assessed with micro-CT, and mechanical properties were evaluated by compression and screw pull-out tests. The overall geometry was well-replicated at scale 1.8, with a volume difference to the original model of <10%. However, scaling factors below 1.8 gave major print artefacts, and a low accuracy in trabecular thickness distribution. A comparison of the model-print overlap showed printing inaccuracies of similar to 20% for the 1.8 scale, visible as a loss of smaller details. SLA-printed parts exhibited a higher pull-out strength compared to existing synthetic models (Sawbones (TM)), and a lower strength compared to cadaveric specimens and fused deposition modelling (FDM)-printed parts in poly (lactic acid). In conclusion, for the same 3D model, SLA enabled higher resolution and printing of smaller scales compared to results reported by FDM.
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| 10. |
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| 11. |
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| 12. |
- Lewin, Catharina, et al.
(författare)
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Utlandsföddas mobilitet och resvanor i svensk trafikmiljö
- 2006
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this study was to increase knowledge concerning the situation of foreign-born in the Swedish transportation system and analyze their mobility and travel patterns. Foreign-born are defined as people born in another country than Sweden, but who have received residence permit and are registered in a Swedish municipality. The results are based on a literature review, register data, group interviews as well as a comprehensive survey. Approximately 12% of Sweden's inhabitants were born in another country. Register data show that the proportion of foreign-born that possess driver's licences and vehicles is lower than among Swedish-born, which limits the ability to travel among this group. The target group for the survey was foreign-born men and women who had relatively recently arrived in Sweden. The survey studied such factors as how they travel on short and longer trips in Sweden, their possession of vehicles and driver's licences and their feeling of safety when using different travel modes. The survey was answered by 3,215 students at special courses in Swedish for immigrants (svenska för invandrare, sfi) from 34 municipalities in different parts of Sweden. Half of the respondents came to Sweden less than two years prior to answering the survey in 2005. The respondents represented 136 different countries of origin. Comparisons have been made both between men and women, and between eight different zones with regards to where the respondents were born. Of the respondents, approximately 60% were women and almost half were 25-34 years old. Results show that approximately 45% of the men surveyed had a driver's licence that was permitted to be used in Sweden, compared to one in five women. The survey showed that the largest obstacles to getting a Swedish driver's licence was that it was expensive and that the language is difficult. Whereas 35% of the women answered that they did not know how to ride a bicycle, only 5% of the men provided this answer. Nearly eight of ten respondents claimed they need to learn more about traffic rules and behaviour. They would like information about this in Swedish. The respondents also stated that they prefer written information on signs at bus stops and train stations, as well as on busses and trains instead of only receiving information by loudspeaker. Many of the respondents feel unsafe in various traffic environments; as pedestrians, bicyclists, car drivers, and as passengers on public transportation.
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| 13. |
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| 14. |
- 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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| 15. |
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| 16. |
- Lewin, Susanne, et al.
(författare)
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Bone Volume Assessment Around Dental Implants After Open Maxillary Sinus Elevation Surgery : A Quantitative Approach to CBCT Images
- 2019
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Ingår i: International Journal of Oral & Maxillofacial Implants. - : QUINTESSENCE PUBLISHING CO INC. - 0882-2786 .- 1942-4434. ; 34:2, s. 489-498
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cone beam computed tomography (CBCT) is an important imaging technique in maxillofacial evaluations. However, application-specific image analysis methods aimed at extracting quantitative information from these images need to be further developed. The aim of this study was to provide a robust and objective method that could assess radiologic changes around dental implants after sinus elevation surgery with simultaneous implant placement.Materials and Methods: The study was performed retrospectively on patients fulfilling the inclusion criteria. The included patients had been CBCT scanned preoperatively, at baseline (early after surgery), and 6 months postoperatively. In order to quantify the radiologic changes, an image analysis workflow was developed based on the postoperative baseline and 6-month scans. The workflow included metal artifact reduction, registration, and a standardized protocol for semiautomatic segmentation. Validation of different steps of the method was conducted by comparing scans from all time points. Comparison of constant volumes (eg, screws and bony parts not subjected to change) was used. Additionally, the Dice similarity coefficient (DSC) was used to measure the overlap of the segmentations.Results: The study included nine maxillary sinuses from six patients. The bone formation was quantified and visualized in 3D. In the validation, no significant differences were found for the constant volumes at the different scanning time points. The DSC showed accurate results with values > 0.92.Conclusion: The method presented in this study provides an objective and robust evaluation of bone formation around dental implants. The same methodologies can be applied in other studies of dental CBCT images, eg, for comparison of grafting materials or surgical strategies.
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| 17. |
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| 18. |
- Lewin, Susanne, et al.
(författare)
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Evaluation of bone formation in calcium phosphate scaffolds with μCT-method validation using SEM
- 2017
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Ingår i: Biomedical Materials. - : Institute of Physics (IOP). - 1748-6041 .- 1748-605X. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- There is a plethora of calcium phosphate (CaP) scaffolds used as synthetic substitutes to bone grafts. The scaffold performance is often evaluated from the quantity of bone formed within or in direct contact with the scaffold. Micro-computed tomography (mu CT) allows three-dimensional evaluation of bone formation inside scaffolds. However, the almost identical x-ray attenuation of CaP and bone obtrude the separation of these phases in mu CT images. Commonly, segmentation of bone in mu CT images is based on gray scale intensity, with manually determined global thresholds. However, image analysis methods, and methods for manual thresholding in particular, lack standardization and may consequently suffer from subjectivity. The aim of the present study was to provide a methodological framework for addressing these issues. Bone formation in two types of CaP scaffold architectures (foamed and robocast), obtained from a larger animal study (a 12 week canine animal model) was evaluated by mu CT. In addition, cross-sectional scanning electron microscopy (SEM) images were acquired as references to determine thresholds and to validate the result. mu CT datasets were registered to the corresponding SEM reference. Global thresholds were then determined by quantitatively correlating the different area fractions in the mu CT image, towards the area fractions in the corresponding SEM image. For comparison, area fractions were also quantified using global thresholds determined manually by two different approaches. In the validation the manually determined thresholds resulted in large average errors in area fraction (up to 17%), whereas for the evaluation using SEM references, the errors were estimated to be less than 3%. Furthermore, it was found that basing the thresholds on one single SEM reference gave lower errors than determining them manually. This study provides an objective, robust and less error prone method to determine global thresholds for the evaluation of bone formation in CaP scaffolds.
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| 19. |
- Lewin, Susanne
(författare)
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Functional Aspects of Cranial Implants : Mechanical and Regenerative Properties
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In several neurosurgical procedures, the skull must be temporarily opened. The resulting bone defect can subsequently be reconstructed with a cranial implant. However, the complication rate of this surgical procedure is high (~20%). The most common complication for cranial implants is infection. Currently, the most frequently used implant materials are titanium alloys, PMMA or PEEK. An improved clinical outcome – in terms of increased bone regeneration, vascularization and soft tissue compatibility – could possibly be obtained through the use of bioactive and osteoconductive materials such as calcium phosphates (CaP).This thesis focuses on CaP–titanium composite (CaP–Ti) implants. This recently developed implant type is increasingly used with a promising outcome. However, a thorough understanding of its functional properties is lacking, something that is of high importance for their clinical use, but also for future biomaterial development. The overall aim of this thesis is to increase the knowledge of the in vivo functional aspects of CaP–Ti composite implants, with a specific focus on the mechanical and regenerative properties.The mechanical properties of the implant were investigated experimentally and numerically at quasi-static and impact loading rates. An important finding was that the titanium structure makes the CaP–Ti implant capable of cerebral protection in impact situations comparable to the one that was tested. Moreover, the mechanical response of the CaP–Ti implants could be predicted by the developed numerical models at both quasi-static and impact loading rates. The developed numerical framework makes an important contribution to future evaluations of patient-specific CaP–Ti cranial implant designs in various loading scenarios. A comparison of two additive manufacturing (3D-printing) processes demonstrated that lower geometrical accuracy and higher surface roughness made electron beam produced implants inferior in terms of mechanical strength, as compared to laser melted implants.In order to assess the regenerative properties, the volumetric balance of the implant was investigated by CT in ten patients. After one year, the total volume of the implant had decreased – mainly at the outside of the implants in the direction of the scalp. However, all patients had a volumetric increase at the interface between the implant and the bone defect. In a histological analysis of a retrieval specimen from one of the patients, the volumetric increase could be confirmed as bone regeneration, and the decrease as CaP degradation. Remodeling of the CaP into bone was also observed, but was not detected in the clinical CT. In retrieval specimens from an animal study, it was found that correlation of some µCT cross-sections to histology can result in improved and more robust quantitative µCT evaluations.
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| 20. |
- 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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| 21. |
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| 22. |
- Lewin, Susanne, et al.
(författare)
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Low-Modulus PMMA Has the Potential to Reduce Stresses on Endplates after Cement Discoplasty
- 2022
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Ingår i: Journal of Functional Biomaterials. - : MDPI. - 2079-4983. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Cement discoplasty has been developed to treat patients with advanced intervertebral disc degeneration. In discoplasty, poly(methylmethacrylate) (PMMA) bone cement is injected into the disc, leading to reduced pain and certain spinal alignment correction. Standard PMMA-cements have much higher elastic modulus than the surrounding vertebral bone, which may lead to a propensity for adjacent fractures. A PMMA-cement with lower modulus might be biomechanically beneficial. In this study, PMMA-cements with lower modulus were obtained using previously established methods. A commercial PMMA-cement (V-steady(R), G21 srl) was used as control, and as base cement. The low-modulus PMMA-cements were modified by 12 vol% (LA12), 16 vol% (LA16) and 20 vol% (LA20) linoleic acid (LA). After storage in 37 degrees C PBS from 24 h up to 8 weeks, specimens were tested in compression to obtain the material properties. A lower E-modulus was obtained with increasing amount of LA. However, with storage time, the E-modulus increased. Standard and low-modulus PMMA discoplasty were compared in a previously developed and validated computational lumbar spine model. All discoplasty models showed the same trend, namely a substantial reduction in range of motion (ROM), compared to the healthy model. The V-steady model had the largest ROM-reduction (77%), and the LA20 model had the smallest (45%). The average stress at the endplate was higher for all discoplasty models than for the healthy model, but the stresses were reduced for cements with higher amounts of LA. The study indicates that low-modulus PMMA is promising for discoplasty from a mechanical viewpoint. However, validation experiments are needed, and the clinical setting needs to be further considered.
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| 23. |
- 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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| 24. |
- Lewin, Susanne, et al.
(författare)
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Monetite-based composite cranial implants demonstrate long-term clinical volumetric balance by concomitant bone formation and degradation
- 2021
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Ingår i: Acta Biomaterialia. - : Elsevier. - 1742-7061 .- 1878-7568. ; 128, s. 502-513
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Tidskriftsartikel (refereegranskat)abstract
- The use of calcium phosphates (CaPs) as synthetic bone substitutes should ideally result in a volumetric balance with concomitant bone formation and degradation. Clinical data on such properties is nevertheless lacking, especially for monetite-based CaPs. However, a monetite-based composite implant has recently shown promising cranial reconstructions, with both CaP degradation and bone formation. In this study, the volumetric change at the implant site was quantified longitudinally by clinical computed tomography (CT). The retrospective CT datasets had been acquired postoperatively ( n = 10), in 1-year ( n = 9) and 3-year ( n = 5) follow-ups. In the 1-year follow-up, the total volumetric change at the implant site was-8 +/- 8%. A volumetric increase (bone formation) was found in the implant-bone interface, and a volumetric decrease was observed in the central region (CaP degradation). In the subjects with 2-or 3-year follow-ups, the rate of volumetric decrease slowed down or plateaued. The reported degradation rate is lower than previous clinical studies on monetite, likely due to the presence of pyrophosphate in the monetite-based CaP-formulation. A 31-months retrieval specimen analysis demonstrated that parts of the CaP had been remodeled into bone. The CaP phase composition remained stable, with 6% transformation into hydroxyapatite. In conclusion, this study demonstrates successful bone-bonding between the CaP-material and the recipient bone, as well as a long-term volumetric balance in cranial defects repaired with the monetitebased composite implant, which motivates further clinical use. The developed methods could be used in future studies for correlating spatiotemporal information regarding bone regeneration and CaP degradation to e.g. patient demographics. Statement of significance In bone defect reconstructions, the use of calcium phosphate (CaP) bioceramics ideally results in a volumetric balance between bone formation and CaP degradation. Clinical data on the volumetric balance is nevertheless lacking, especially for monetite-based CaPs. Here, this concept is investigated for a composite cranial implant. The implant volumes were quantified from clinical CT-data: postoperatively, one year and three years postoperatively. In total,-8 +/- 8% ( n = 9) volumetric change was observed after one year. But the change plateaued, with only 2% additional decrease at the 3-year follow-up ( n = 5), indicating a lower CaP degradation rate. Osseointegration was seen at the bone-implant interface, with a 9 +/- 7% volumetric change after one year. This study presented the first quantitative spatiotemporal CT analysis of monetite-based CaPs.
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| 27. |
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| 28. |
- Murtada, S.-I., et al.
(författare)
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Adaptation of active tone in the mouse descending thoracic aorta under acute changes in loading
- 2015
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Ingår i: Biomechanics and Modeling in Mechanobiology. - : Springer Berlin/Heidelberg. - 1617-7959 .- 1617-7940. ; 15, s. 579-592
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Tidskriftsartikel (refereegranskat)abstract
- Arteries can adapt to sustained changes in blood pressure and flow, and it is thought that these adaptive processes often begin with an altered smooth muscle cell activity that precedes any detectable changes in the passive wall components. Yet, due to the intrinsic coupling between the active and passive properties of the arterial wall, it has been difficult to delineate the adaptive contributions of active smooth muscle. To address this need, we used a novel experimental–computational approach to quantify adaptive functions of active smooth muscle in arterial rings excised from the proximal descending thoracic aorta of mice and subjected to short-term sustained circumferential stretches while stimulated with various agonists. A new mathematical model of the adaptive processes was derived and fit to data to describe and predict the effects of active tone adaptation. It was found that active tone was maintained when the artery was adapted close to the optimal stretch for maximal active force production, but it was reduced when adapted below the optimal stretch; there was no significant change in passive behavior in either case. Such active adaptations occurred only upon smooth muscle stimulation with phenylephrine, however, not stimulation with KCl or angiotensin II. Numerical simulations using the proposed model suggested further that active tone adaptation in vascular smooth muscle could play a stabilizing role for wall stress in large elastic arteries.
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| 29. |
- Riben, Christopher, et al.
(författare)
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Quantification of Bone Height and Bone Volume Around Dental Implants After Open Maxillary Sinus Elevation Surgery Using CBCT.
- 2023
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Ingår i: International Journal of Oral & Maxillofacial Implants. - : Quintessence Publishing. - 0882-2786 .- 1942-4434. ; 38:4, s. 789-800
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To assess, using CBCT, the volume and height of bone formation after open maxillary sinus elevation without the use of grafts.Materials and Methods: The study was retrospective and included 24 patients with a total of 67 implants. CBCT examinations were conducted at baseline (0 to 43 days postsurgery) and after an average healing period of 6.2 months (range: 5.1 to 7.8 months). The image analysis included metal artifact reduction, registration, and a standardized protocol for segmenting the anatomical structures of the maxillary sinus, including calculating the 3D volumetric changes after bone formation. Conventional manual 2D measurement of vertical bone formation was executed for comparison. Clinical factors assumed to be relevant for bone formation were obtained from patient medical records.Results: One implant was lost before prosthetic loading, representing an early implant loss rate of 1.5%. Differences in intra- and interexaminer reproducibility were registered for the conventional 2D method (P < .05). The average vertical bone formation measured with the 2D method was 4.8 mm (4.6 to 5.0 mm), covering 60.2% of the implant height within the sinus. The average volumetric bone formation measured with the developed 3D image-analysis method was 801 mm3 in total and 195 mm3 in a restricted region around each implant. Bone formation was registered in 62% of the volume of the restricted region. A correlation regarding bone formation was found between the two methods (R2 = 0.705). Clinical factors such as age, smoking, general health, and postoperative complications did not correlate with the amount of bone formed.Conclusion: CBCT image analysis is a promising method for objective 3D evaluation of bone formation after sinus elevation. A correlation was seen between the manually measured bone height (2D) and the bone volume in a restricted region around each implant using the developed method (3D). Reducing visual interpretation minimizes errors related to examiner reliability. Clinical factors did not significantly affect the volumetric bone formation.
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| 30. |
- Scott, Robert A., et al.
(författare)
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An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans
- 2017
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:11, s. 2888-2902
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Tidskriftsartikel (refereegranskat)abstract
- To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 x 10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.
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