| 1. |
- Forsell, Caroline, et al.
(författare)
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A method for determining minimal sets of markers for the estimation of center of mass, linear and angular momentum
- 2009
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Ingår i: Journal of Biomechanics. - : Elsevier BV. - 0021-9290 .- 1873-2380. ; 42:3, s. 361-365
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Tidskriftsartikel (refereegranskat)abstract
- A new method is proposed for finding small sets of points on the body giving sufficient information for estimating the whole body center of mass (CoM), as well as the linear momenta (LM) and angular momenta (AM). In the underlying model each point (whose trajectory is tracked by a marker) is a point mass: Hence the body is represented by a simple system of point masses. The first step is to determine the appropriate set of points and the mass of each point, which is assumed to be specific for the movement performed. The distribution of the mass to each marker is determined from training data for which the true (or reference) trajectories of the CoM, LM or AM are known. This leads to a quadratic optimization problem with inequality constraints. The use of the method is demonstrated on data from discus throw. Results indicate reasonably small errors, considering the magnitude of other error Sources, in CoM position (average magnitude of estimation error 1-2 cm), and moderate errors in AM (13-20% of peak Value).
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| 2. |
- Forsell, Caroline, et al.
(författare)
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Biomechanical Properties of the Thoracic Aneurysmal Wall : Differences Between Bicuspid Aortic Valve and Tricuspid Aortic Valve Patients
- 2014
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Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975 .- 1552-6259. ; 98:1, s. 65-71
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Tidskriftsartikel (refereegranskat)abstract
- Background. The prevalence for thoracic aortic aneurysms (TAAs) is significantly increased in patients with a bicuspid aortic valve (BAV) compared with patients who have a normal tricuspid aortic valve (TAV). TAA rupture is a life-threatening event, and biomechanics-based simulations of the aorta may help to disentangle the molecular mechanism behind its development and progression. The present study used polarized microscopy and macroscopic in vitro tensile testing to explore collagen organization and mechanical properties of TAA wall specimens from BAV and TAV patients. Methods. Circumferential sections of aneurysmal aortic tissue from BAV and TAV patients were obtained during elective operations. The distribution of collagen orientation was captured by a Bingham distribution, and finite element models were used to estimate constitutive model parameters from experimental load-displacement curves. Results. Collagen orientation was almost identical in BAV and TAV patients, with a highest probability of alignment along the circumferential direction. The strength was almost two times higher in BAV samples (0.834 MPa) than in TAV samples (0.443 MPa; p < 0.001). The collagen-related stiffness (C-f) was significantly increased in BAV compared with TAV patients (C-f = 7.45 MPa vs 3.40 MPa; p = 0.003), whereas the elastin-related stiffness was similar in both groups. A trend toward a decreased wall thickness was seen in BAV patients (p = 0.058). Conclusions. The aneurysmal aortas of BAV patients show a higher macroscopic strength, mainly due to an increased collagen-related stiffness, compared with TAV patients. The increased wall stiffness in BAV patients may contribute to the higher prevalence for TAAs in this group.
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| 3. |
- Forsell, Caroline, 1982-
(författare)
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Failure of vascular tissue with applications to the aneurysm wall, carotid plaque and myocardial tissue
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiovascular disease is the leading cause of death in the modern world. Examples are thoracic aortic aneurysm (TAA), abdominal aortic aneurysm (AAA) and stroke due to plaque rupture. Failure in soft tissues caused by medical devices is also a medical challenge. In all these cardiovascular events a better prediction of failure of the tissue and a better understanding about the tissue properties will help in predicament and treatment. For example the diameter-based indication for surgical repair of AAA and TAAs is not sufficient and refined methods are needed. In this thesis failures of some soft vascular tissues, was studied. Experiments have been combined with numerical modeling to understand the elastic and failure properties of AAA, TAA and plaque tissue as well as the ventricular wall. Vascular tissue is anisotropic, time-dependent, nonlinear and shows large deformations. Among others this thesis showed the importance of viscoelasticity which motivates to develop a new continuum mechanical framework. In addition a large part of this thesis dealt with anisotropy of vascular tissue. For the first time the collagen orientation distribution in the AAA wall has been identified. Collagen and its distribution orientation is also an important feature of this tissue. There was a correlation between the strength and stiffness of the AAA samples with the decreasing wall thickness. Increased stiffness was found in the aortic wall of patients with chronic obstructive pulmonary disease (COPD) compared to patients that did not have COPD. As well as difference in stiffness of TAA tissue, in patients with non-pathologic and pathologic aortic valves. Some of the findings in this thesis could have a long-term consequence for management of risk of rupture in AAA, TAA and plaque.
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| 4. |
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| 5. |
- Forsell, Charlotte, et al.
(författare)
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Genetic association to the amyloid plaque associated protein gene COL25A1 in Alzheimer's disease
- 2010
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Ingår i: Neurobiology of Aging. - Fayetteville, N.Y. : Ankho International. - 0197-4580 .- 1558-1497. ; 31:3, s. 409-415
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Tidskriftsartikel (refereegranskat)abstract
- The COL25A1 gene, located in 4q25, encodes the CLAC protein, which has been implicated in Alzheimer's disease (AD) pathogenesis. CLAC was originally identified in amyloid preparations from AD brain and has been shown to be associated with amyloid plaques, inhibition of Abeta-fibril elongation and increased protease resistance of Abeta-fibrils through direct binding to Abeta. These biochemical data as well as the genomic location of the COL25A1 gene in chromosome 4q25 where we previously have reported a weak linkage-signal in Swedish AD families encouraged us to perform a case-control association study of two LD blocks in COL25A1 using 817 AD cases and 364 controls. The LD blocks cover a putative Abeta-binding motif and the variable 3' end of the gene. The analyses indicated association to three of eight analysed SNPs. We found further support for the association by replication in a Swedish population-based longitudinal sample set (n=926). Thus, in addition to the biochemical data, there is now genetic evidence of association between COL25A1 and risk for Alzheimer's disease.
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| 6. |
- Forsell, Caroline, et al.
(författare)
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Impact of material anisotropy on deformation of myocardial tissue due to pacemaker electrodes
- 2011
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Ingår i: ASME 2011 Summer Bioengineering Conference, SBC 2011. - 9780791854587 ; , s. 789-790
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Konferensbidrag (refereegranskat)abstract
- A Pacemaker electrode can penetrate the heart wall, and to design a penetration-resistent lead tip sound knowledge regarding failure of ventricular tissue is required. Numerical simulations can be particular helpful in that respect, but depend on a reliable constitutive description for ventricular tissue. In this study an anisotropic hyperelastic model for the myocardium has been implemented and compared to predictions from an isotropic description. Specifically, the response due to pushing a rigid punch into the myocardium was studied. Results between anisotropic and isotropic descriptions of the myocardium differed significantly, which justified the implementation of an anisotropic model for the myocardium.
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| 7. |
- Forsell, Caroline, et al.
(författare)
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Modeling of myocardial splitting due to deep penetration
- 2010
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Ingår i: CONSTITUTIVE MODELS FOR RUBBER VI. - BOCA RATON : CRC PRESS-TAYLOR & FRANCIS GROUP. - 9780415563277 ; , s. 449-452
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Konferensbidrag (refereegranskat)abstract
- The risk for pacemaker lead perforation, a rare but serious clinical complication, is thought to be minimized by perforation resistant device design. Fracture properties of ventricular tissue play a central role in such optimization studies, however, this information is currently not provided by the open literature; even failure models for soft biological tissue in general are rare. Incompressible finite deformations, material nonlinearity and time-dependent anisotropic properties require sophisticated approaches to identify and model failure of such a material. In this study we investigated myocardial failure due to deep penetration, where previously collected data from in-vitro experiments are integrated in a non-linear Finite Element model. In details, the proposed model describes tissue splitting by a cohesive process zone, and hence, tissue failure is modeled as a gradual process, where all inelastic phenomena are accumulated and mathematically captured by a traction separation law. The cohesive zone is embedded in a fibrous bulk material thought to capture the properties of passive myocardial tissue, where a transversely isotropic hyper-elastic constitutive description proposed in the literature was utilized. The developed numerical model integrates latest experimental data and is able to replicate quantitative and qualitative data from ventricular penetration experiments.
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| 8. |
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| 9. |
- Forsell, Caroline, et al.
(författare)
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Numerical simulation of the failure of ventricular tissue due to deep penetration : The impact of constitutive properties
- 2011
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Ingår i: Journal of Biomechanics. - : Elsevier BV. - 0021-9290 .- 1873-2380. ; 44:1, s. 45-51
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Tidskriftsartikel (refereegranskat)abstract
- Lead perforation is a rare but serious clinical complication of pacemaker implantation, and towards understanding this malfunction, the present study investigated myocardial failure due to deep penetration by an advancing rigid punch. To this end, a non-linear Finite Element model was developed that integrates constitutive data published in the literature with information from in vitro tensile testing in cross-fibre direction of porcine myocardial tissue. The Finite Element model considered non-linear, isotropic and visco-elastic properties of the myocardium, and tissue failure was phenomenologically described by a Traction Separation Law. In vitro penetration testing of porcine myocardium was used to validate the Finite Element model, and a particular objective of the study was to investigate the impact of different constitutive parameters on the simulated results. Specifically, results demonstrated that visco-elastic properties of the tissue strongly determine the failure process, whereas dissipative effects directly related to failure had a minor impact on the simulation results. In addition, non-linearity of the bulk material did not change the predicted peak penetration force and the simulations did not reveal elastic crack-tip blunting. The performed study provided novel insights into ventricular failure due to deep penetration, and provided useful information with which to develop numerical failure models.
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| 10. |
- Forsell, Caroline, et al.
(författare)
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Teachers’ Attitudes to Teaching Introductory Solid Mechanics in Upper Secondary School
- 2021
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Ingår i: Techneserien. - 1238-951X. ; 28:2, s. 448-454
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Tidskriftsartikel (refereegranskat)abstract
- In upper secondary school in Sweden, the students in the technology programme take an introductory course that aims at providing a broad introduction to the engineering field. The course’s curriculum is open to various interpretations and solid mechanics is not included explicitly, but it is taught within the course by many teachers. Previous studies of teachers’ attitudes towards other subjects showed that confidence is commonly influenced by subject knowledge. Thereby teachers’ knowledge affects their teaching and their students’ learning opportunities. The present study was based on interviews with 13 technology teachers, teaching in upper secondary school. The interviews concerned their attitudes towards teaching introductory solid mechanics and included those who taught solid mechanics, and those who did not. Those who taught solid mechanics did so through personal choice, because of influence from colleagues and local traditions, or because they took it for granted. Many among them expressed interest in solid mechanics and thought it to be of importance for future engineers. They had high self-efficacy and low anxiety regarding the subject. Those who did not teach solid mechanics omitted it mainly because of an experienced lack of knowledge. They let their students develop problem-solving and calculation abilities within other areas, which the teachers themselves felt more confident in. They ranked the importance of solid mechanics for future engineers as medium or low. The study indicates that technology teachers’ attitudes towards various engineering disciplines may affect their teaching and that studying those attitudes is important to understand the enacted school subjects.
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| 11. |
- Forsell, Caroline, et al.
(författare)
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The impact of constitutive properties on myocardial tissue perforation
- 2010
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Konferensbidrag (refereegranskat)abstract
- Introduction Acute or delayed lead perforation is a rare but serious complication of pacemaker implantation with numerous case reports and case series known [1]. A perforation-resistant lead tip design requires detailed knowledge regarding the mechanical failure of the ventricular wall. Like many other soft biological tissues, ventricular tissue exhibits complex mechanical properties like incompressibility, finite deformability, inhomogeneity, material non-linearity, anisotropy, strain rate-dependency, and a constitutive model should reflect that to the required degree of completeness. Within this work we investigate the failure mechanisms of myocardial penetration by advancing a rigid punch, conditions thought to be related to pacemaker lead perforation. Specifically, the impact of constitutive parameters related to the bulk material and the failure zone is analyzed. Method A single penetration site of our previous penetration experiment of biaxially-stretched myocardial tissue [2] was models by the non-linear Finite Element Method (ABAQUS, Dassault Systèmes). To this end a visco-elastic description was applied and a previously reported anisotropic constitutive model for myocardial tissue [3] was implemented using the user material model interface. All failure related inelastic deformations were lumped into a fracture process zone and captured by a triangular cohesive traction separation law. To this end the cohesive strength of ventricular tissue was experimentally determined by tensile testing in cross-fiber direction of porcine myocardial tissue. Simulated results with different visco-elastic and failure properties, i.e. by varying the associated sets of constitutive parameters of the myocardial tissue were investigated. Results and Conclusions Results demonstrated that visco-elastic properties of the myocardial tissue strongly determine the failure of myocardial tissue due to deep penetration. This finding is in line with failure of rubber-like materials, where visco-elastic energy dissipation in front of the crack tip was found to be an important factor of energy dissipation [4]. In contrast dissipative effects which are directly related to failure (i.e. captured by the cohesive zone model) had a minor impact on the simulated penetration force displacement characteristics. Likewise, non-linearity and anisotropy of the bulk material did not change the predicted peak penetration force and the simulations did not reveal elastic crack-tip blunting. The proposed numerical model integrates experimental data from different studies and allows a detailed investigation of failure related to pacemaker lead perforation. Results from the study provided novel insights into ventricular failure due to deep penetration, which might also be related to other soft biological tissues and helpful to design penetration resistant pacemaker leads. References [1] M.N. Khan, et. al. Pacing and Clinical Electrophysiology, 28, 251-253, 2005. [2] T.C. Gasser et. al. J. Biomech., 42, 626-633, 2009. [3] J. D. Humphrey et al., J. Biomech. Engrg., 112, 340-346, 1990. [4] B.N.J. Persson,et. Al ., J.Phys. Condens. Matter., 17, R1071-R1142, 2005.
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| 12. |
- Forsell, Caroline, et al.
(författare)
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The Quasi-Static Failure Properties of the Abdominal Aortic Aneurysm Wall Estimated by a Mixed Experimental-Numerical Approach
- 2012
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Ingår i: Annals of Biomedical Engineering. - : Springer-Verlag New York. - 0090-6964 .- 1573-9686. ; 41:7, s. 1554-1566
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Tidskriftsartikel (refereegranskat)abstract
- Assessing the risk for abdominal aortic aneurysm (AAA) rupture is critical in the management of aneurysm patients and an individual assessment is possible with the biomechanical rupture risk assessment. Such an assessment could potentially be improved by a constitutive AAA wall model that accounts for irreversible damage-related deformations. Because of that the present study estimated the elastic and inelastic properties of the AAA wall through a mixed experimental-numerical approach. Specifically, finite element (FE) models of bone-shaped tensile specimens were used to merge data from failure testing of the AAA wall with their measured collagen orientation distribution. A histo-mechanical constitutive model for collagen fibers was employed, where plastic fibril sliding determined not only remaining deformations but also weakening of the fiber. The developed FE models were able to replicate the experimentally recorded load-displacement property of all 16 AAA wall specimens that were investigated in the study. Tensile testing in longitudinal direction of the AAA defined a Cauchy strength of 569(SD 411) kPa that was reached at a stretch of 1.436(SD 0.118). The stiffness and strength of specimens decreased with the wall thickness and were elevated (p = 0.018; p = 0.030) in patients with chronic obstructive pulmonary disease (COPD). Smoking affected the tissue parameters that were related to the irreversible deformation response, and no correlation with gender and age was found. The observed effects on the biomechanical properties of the AAA wall could have long-term consequences for the management of aneurysm patients, i.e., specifically they might influence future AAA rupture risk assessments. However, in order to design appropriate clinical validation studies our findings should firstly be verified in a larger patient cohort.
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| 13. |
- Forsell, Erik, et al.
(författare)
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Internet delivered cognitive behavior therapy for antenatal depression : A randomised controlled trial
- 2017
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Ingår i: Journal of Affective Disorders. - Amsterdam, Netherlands : Elsevier. - 0165-0327 .- 1573-2517. ; 221, s. 56-64
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Tidskriftsartikel (refereegranskat)abstract
- Major depression occurs in 5-10% of pregnancies and is associated with many negative effects for mother and child, yet treatment options are scarce. To our knowledge, this is the first published randomised controlled trial on Internet delivered Cognitive Behavior Therapy (ICBT) for this group.Objective: To test the efficacy of a pregnancy adapted version of an existing 10-week ICBT-program for depression as well as assessing acceptability and adherence.Design: Randomised controlled trial.Setting: Online and telephone.Population or sample: Self-referred pregnant women (gestational week 10-28 at intake) currently suffering from major depressive disorder.Methods: 42 pregnant women (gestational week 12-28) with major depression were randomised to either treatment as usual (TAU) provided at their antenatal clinic or to ICBT as an add-on to usual care.Main outcome measures: The primary outcome was depressive symptoms measured with the Montgomery-Asberg depression rating scale-self report (MADRS-S). The Edinburgh Postnatal Depression Scale and measures of anxiety and sleep were used. Credibility, satisfaction, adherence and utilization were also assessed.Results: The ICBT group had significantly lower levels of depressive symptoms post treatment (p < 0.001, Hedges g = 1.21) and were more likely to be responders (i.e. achieve a statistically reliable improvement) (RR = 0.36; p = 0.004). Measures of treatment credibility, satisfaction, utilization, and adherence were comparable to implemented ICBT for depression.Limitations: Small sample size and no long-term evaluation.Conclusion: Pregnancy adapted ICBT for antenatal depression is feasible, acceptable and efficacious. These results need to be replicated in larger trials to validate these promising findings.
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| 14. |
- Gasser, Christian, et al.
(författare)
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The numerical implementation of invariant-based viscoelastic formulations at finite strains. An anisotropic model for the passive myocardium
- 2011
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Ingår i: Computer Methods in Applied Mechanics and Engineering. - : Elsevier BV. - 0045-7825 .- 1879-2138. ; 200:49-52, s. 3637-3645
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Tidskriftsartikel (refereegranskat)abstract
- The present study developed a conceptual framework for finite strain viscoelasticity thought to be suitable to capture the salient features of a class of passive soft biological tissues like the myocardium. A superposition of a Maxwell Body and an Elastic Body defines the viscoelastic continuum, and its deformation is related to two independent reference configurations. The reference configuration of the Maxwell Body moves in space as it is described (apart from rigid body rotation) by a rate equation in strain space, and stores the history of the deformation. At thermodynamic equilibrium the reference configuration of the Maxwell Body coincides with the current configuration of the continuum. The Helmholtz free energy is expressed as a function of two independent strain variables and entirely renders the constitution of the viscoelastic body. Although this view is to some extent different from reported viscoelastic concepts for finite strains, its linearization around the thermodynamic equilibrium coincides with earlier suggested viscoelastic models. The linearized viscoelastic model has been implemented for a particular anisotropic constitutive model for the passive myocardium. Non-negative dissipation of the model is guaranteed. Material parameters were estimated from in vitro testing of porcine myocardium and the response due to pushing a rigid punch into the myocardium was studied. Results between anisotropic and isotropic descriptions of the myocardium differed significantly, which justified the implementation of an anisotropic model for the myocardium.
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| 15. |
- Gasser, T. Christian, et al.
(författare)
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Spatial orientation of collagen fibers in the abdominal aortic aneurysm's wall and its relation to wall mechanics
- 2012
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 8:8, s. 3091-3103
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Tidskriftsartikel (refereegranskat)abstract
- Collagen is the most abundant protein in mammals and provides the abdominal aortic aneurysm (AAA) wall with mechanical strength, stiffness and toughness. Specifically, the spatial orientation of collagen fibers in the wall has a major impact on its mechanical properties. Apart from valuable microhistological information, this data can be integrated by histomechanical constitutive models thought to improve biomechanical simulations, i.e. to improve the biomechanical rupture risk assessment of AAAs. Tissue samples (n = 24) from the AAA wall were harvested during elective AAA repair, fixated, embedded, sectioned and investigated by polarized light microscopy. The birefringent properties of collagen were reinforced by picrosirius red staining and the three-dimensional collagen fiber orientations were identified with a universal rotary stage. Two constitutive models for collagen fibers were used to integrate the identified structural information in a macroscopic AAA wall model. The collagen fiber orientation in the AM wall was widely dispersed and could be captured by a Bingham distribution function (kappa(1) = 11.6, kappa(2) = 9.7). The dispersion was much larger in the tangential plane than in the cross-sectional plane, and no significant difference between the medial and adventitial layers could be identified. The layered directional organization of collagen in normal aortas was not evident in the AAA. The collagen organization identified, combined with constitutive descriptions of collagen fibers that depend on its orientation, explain the anisotropic (orthotropic) mechanical properties of the AAA wall. The mechanical properties of collagen fibers depend largely on their undulation, which is an important structural parameter that requires further experimental investigation.
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| 16. |
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| 17. |
- Heiland, Vincent M., et al.
(författare)
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Identification of carotid plaque tissue properties using an experimental-numerical approach
- 2013
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161 .- 1878-0180. ; 27, s. 226-238
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Tidskriftsartikel (refereegranskat)abstract
- A biomechanical stress analysis could help to identify carotid plaques that are vulnerable to rupture, and hence reduce the risk of thrombotic strokes. Mechanical stress predictions critically depend on the plaque's constitutive properties, and the present study introduces a concept to derive viscoelastic parameters through an experimental-numerical approach. Carotid plaques were harvested from two patients during carotid endarterectomy (CEA), and, in total, nine test specimens were investigated. A novel in-vitro mechanical testing protocol, which allows for dynamic testing, keeping the carotid plaque components together, was introduced. Macroscopic pictures overlaid by histological stains allowed for the segmentation of plaque tissues, in order to develop high-fidelity and low-fidelity Finite Element Method (FEM) models of the test specimens. The FEM models together with load-displacement data from the mechanical testing were used to extract constitutive parameters through inverse parameter estimation. The applied inverse parameter estimation runs in stages, first addressing the hyperelastic parameters then the viscoelastic ones. Load-displacement curves from the mechanical testing showed strain stiffening and viscoelasticity, as is expected for both normal and diseased carotid tissue. The estimated constitutive properties of plaque tissue were comparable to previously reported studies, Due to the highly non-linear elasticity of vascular tissue, the applied parameter estimation approach is, as with many similar approaches, sensitive to the initial guess of the parameters.
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| 18. |
- Polzer, S., et al.
(författare)
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Automatic identification and validation of planar collagen organization in the aorta wall with application to abdominal aortic aneurysm
- 2013
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Ingår i: Microscopy and Microanalysis. - 1431-9276 .- 1435-8115. ; 19:6, s. 1395-1404
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Tidskriftsartikel (refereegranskat)abstract
- Arterial physiology relies on a delicate three-dimensional (3D) organization of cells and extracellular matrix, which is remarkably altered by vascular diseases like abdominal aortic aneurysms (AAA). The ability to explore the micro-histology of the aorta wall is important in the study of vascular pathologies and in the development of vascular constitutive models, i.e., mathematical descriptions of biomechanical properties of the wall. The present study reports and validates a fast image processing sequence capable of quantifying collagen fiber organization from histological stains. Powering and re-normalizing the histogram of the classical fast Fourier transformation (FFT) is a key step in the proposed analysis sequence. This modification introduces a powering parameter w, which was calibrated to best fit the reference data obtained using classical FFT and polarized light microscopy (PLM) of stained histological slices of AAA wall samples. The values of w = 3 and 7 give the best correlation (Pearson's correlation coefficient larger than 0.7, R 2 about 0.7) with the classical FFT approach and PLM measurements. A fast and operator independent method to identify collagen organization in the arterial wall was developed and validated. This overcomes severe limitations of currently applied methods like PLM to identify collagen organization in the arterial wall.
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| 19. |
- Sillén, Anna, et al.
(författare)
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Expanded high-resolution genetic study of 109 Swedish families with Alzheimer's disease
- 2008
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 16:2, s. 202-208
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is a neurodegenerative disease that affects approximately 20 million persons all over the world. There are both sporadic and familial forms of AD. We have previously reported a genome-wide linkage analysis on 71 Swedish AD families using 365 genotyped microsatellite markers. In this study, we increased the number of individuals included in the original 71 analysed families besides adding 38 new families. These 109 families were genotyped for 1100 novel microsatellite markers. The present study reports on the linkage data generated from the non-overlapping genotypes from the first genome scan and the genotypes of the present scan, which results in a total of 1289 successfully genotyped markers at an average density of 2.85 cM on 468 individuals from 109 AD families. Non-parametric linkage analysis yielded a significant multipoint LOD score in chromosome 19q13, the region harbouring the major susceptibility gene APOE, both for the whole set of families (LOD = 5.0) and the APOE epsilon 4-positive subgroup made up of 63 families (LOD = 5.3). Other suggestive linkage peaks that were observed in the original genome scan of 71 Swedish AD families were not detected in this extended analysis, and the previously reported linkage signals in chromosomes 9, 10 and 12 were not replicated.
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| 20. |
- Sillén, Anna, et al.
(författare)
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Linkage Analysis of Autopsy-Confirmed Familial Alzheimer Disease Supports an Alzheimer Disease Locus in 8q24
- 2011
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 31:2, s. 109-118
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: We have previously reported the results of an extended genome-wide scan of Swedish Alzheimer disease (AD)-affected families; in this paper, we analyzed a subset of these families with autopsy-confirmed AD. Methods: We report the fine-mapping, using both microsatellite markers and single-nucleotide polymorphisms (SNPs), in the observed maximum logarithm of the odds (LOD)-2 unit (LODmax-2) region under the identified linkage peak, linkage analysis of the fine-mapping data with additionally analyzed pedigrees, and association analysis of SNPs selected from candidate genes in the linked interval. The subset was made on the criterion of at least one autopsy-confirmed AD case per family, resulting in 24 families. Results: Linkage analysis of a family subset having at least one autopsy-confirmed AD case showed a significant nonparametric single-point LOD score of 4.4 in 8q24. Fine-mapping under the linkage peak with 10 microsatellite markers yielded an increase in the multipoint (mpt) LOD score from 2.1 to 3.0. SNP genotyping was performed on 21 selected candidate transcripts of the LODmax-2 region. Both family-based association and linkage analysis were performed on extended material from 30 families, resulting in a suggestive linkage at peak marker rs6577853 (mpt LOD score = 2.4). Conclusion: The 8q24 region has been implicated to be involved in AD etiology.
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| 21. |
- Sillén, Anna, et al.
(författare)
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Linkage to 20p13 including the ANGPT4 gene in families with mixed Alzheimer's disease and vascular dementia
- 2010
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Ingår i: Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1434-5161 .- 1435-232X. ; 55:10, s. 649-655
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed at identifying novel susceptibility genes for a mixed phenotype of Alzheimer's disease and vascular dementia. Results from a genome scan showed strongest linkage to 20p13 in 18 families, and subsequent fine mapping was performed with both microsatellites and single-nucleotide polymorphisms in 18 selected candidate transcripts in an extended sample set of 30 families. The multipoint linkage peak was located at marker rs2144151 in the ANGPT4 gene, which is a strong candidate gene for vascular disease because of its involvement in angiogenesis. Although the significance of the linkage decreased, we find this result intriguing, considering that we included additional families, and thus the reduced linkage signal may be caused by genetic heterogeneity.
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| 22. |
- Sundling, Christopher, et al.
(författare)
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B cell profiling in malaria reveals expansion and remodeling of CD11c+ B cell subsets
- 2019
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Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 4:9
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Tidskriftsartikel (refereegranskat)abstract
- Humoral immunity is important in limiting clinical disease in malaria, yet the longitudinal B cell response to infection remains unclear. We performed a 1-year prospective study in patients treated for acute Plasmodium fakiporum malaria for the first time or with previous exposure to the disease. Using an unbiased exploratory approach with mass cytometry, followed by targeted flow cytometry, we found that approximately 80% of mature B cells that proliferated in response to acute infection expressed CD11c. Only approximately 40% of CD11c+ B cells displayed an atypical B cell phenotype, with the remaining cells primarily made up of activated and resting memory B cells. The CD11c+ B cells expanded rapidly following infection, with previous exposure to malaria resulting in a significantly larger increase compared with individuals with primary infection. This was attributed to an expansion of switched CD11c+ B cells that was absent in primary infected individuals. The rate of contraction of the CD11c+ B cell compartment was independent of previous exposure to malaria and displayed a slow decay, with a half-life of approximately 300 days. Collectively, these results identify CD11c as a marker of B cells responding to malaria and further highlight differences in primary and secondary B cell responses during infection.
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| 23. |
- Westerlund, Marie, et al.
(författare)
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Altered enzymatic activity and allele frequency of OMI/HTRA2 in Alzheimer's disease.
- 2011
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Ingår i: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Wiley. - 1530-6860. ; 25:4, s. 1345-52
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Tidskriftsartikel (refereegranskat)abstract
- The serine-protease OMI/HTRA2, required for several cellular processes, including mitochondrial function, autophagy, chaperone activity, and apoptosis, has been implicated in the pathogenesis of both Alzheimer's disease (AD) and Parkinson's disease (PD). Western blot quantification of OMI/HTRA2 in frontal cortex of patients with AD (n=10) and control subjects (n=10) in two separate materials indicated reduced processed (active, 35 kDa) OMI/HTRA2 levels, whereas unprocessed (50 kDa) enzyme levels were not significantly different between the groups. Interestingly, the specific protease activity of OMI/HTRA2 was found to be significantly increased in patients with AD (n=10) compared to matched control subjects (n=10) in frontal cortex in two separate materials. Comparison of OMI/HTRA2 mRNA levels in frontal cortex and hippocampus, two brain areas particularly affected by AD, indicated similar levels in patients with AD (n=10) and matched control subjects (n=10). In addition, we analyzed the occurrence of the OMI/HTRA2 variants A141S and G399S in Swedish case-control materials for AD and PD and found a weak association of A141S with AD, but not with PD. In conclusion, our genetic, histological, and biochemical findings give further support to an involvement of OMI/HTRA2 in the pathology of AD; however, further studies are needed to clarify the role of this gene in neurodegeneration.
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