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| 2. |
- Andersson, Malte, 1941, et al.
(författare)
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”Minskande befolkning är inte problemet”
- 2020
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Ingår i: Dagens Nyheter. ; :1 augusti, DN-debatt
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Nätverket Population Matters Sweden: En uppmärksammad studie i The Lancet pekar mot en lägre befolkningsökning i världen än tidigare prognoser. Men en miljard människor till är fortfarande långt över vad jorden klarar. Befolkningstrenden måste snarare vända neråt, och det kräver åtgärder för att stärka kvinnors rättigheter världen över.
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| 3. |
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| 4. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 5. |
- Ekström, Lars, 1959, et al.
(författare)
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In vivo porcine intradiscal pressure as a function of external loading
- 2004
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Ingår i: J Spinal Disord Tech. - 1536-0652. ; 17:4, s. 312-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Spinal loading during daily activity as it relates to the ability of the intervertebral disc to sustain its integrity has been a major issue in spinal research. The purpose of this investigation was to establish the relationship between the intervertebral disc pressure in the nucleus and the load applied to the motion segment in an in vivo porcine model. METHODS: Nine domestic pigs were used in this study. A miniaturized servohydraulic testing machine was affixed to the lumbar spine via four intrapedicular screws, which were inserted bilaterally into the L2 and L3 vertebrae. A pressure needle was inserted through the lateral part of the L2-L3 disc annulus and into the nucleus pulposus. Force, deformation, and intradiscal pressure data were collected during a loading scheme that consisted of applying a set of constant loads in increasing order, that is, 50, 100, 150, 200, and 250 N. Each load was applied for 30 seconds followed by 30-second restitution. RESULTS: Intradiscal nucleus pressure was found to correlate to the applied load in all cases. Linear regression analyses resulted in the following equation: intradiscal pressure (MPa) = 0.08 + 1.25E(-3)(load, N), r(2) = 0.81, n = 8. Intradiscal pressure was also highly linearly dependent on the stress. The intrinsic intradiscal pressure was found to be 81 +/- 5 kPa. The results also indicated that the pressure within the disc exhibited a creep behavior. CONCLUSION: In conclusion, pressure in the nucleus of the porcine intervertebral disc was linearly related to the applied load and stress.
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| 6. |
- Ekström, Lars, 1959, et al.
(författare)
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Intervertebral disc response to cyclic loading--an animal model.
- 1996
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Ingår i: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine. - 0954-4119. ; 210:4, s. 249-58
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Tidskriftsartikel (refereegranskat)abstract
- The viscoelastic response of a lumbar motion segment loaded in cyclic compression was studied in an in vivo porcine model (N = 7). Using surgical techniques, a miniaturized servohydraulic exciter was attached to the L2-L3 motion segment via pedicle fixation. A dynamic loading scheme was implemented, which consisted of one hour of sinusoidal vibration at 5 Hz, 50 N peak load, followed by one hour of restitution at zero load and one hour of sinusoidal vibration at 5 Hz, 100 N peak load. The force and displacement responses of the motion segment were sampled at 25 Hz. The experimental data were used for evaluating the parameters of two viscoelastic models: a standard linear solid model (three-parameter) and a linear Burger's fluid model (four-parameter). In this study, the creep behaviour under sinusoidal vibration at 5 Hz closely resembled the creep behaviour under static loading observed in previous studies. Expanding the three-parameter solid model into a four-parameter fluid model made it possible to separate out a progressive linear displacement term. This deformation was not fully recovered during restitution and is therefore an indication of a specific effect caused by the cyclic loading. High variability was observed in the parameters determined from the 50 N experimental data, particularly for the elastic modulus E1. However, at the 100 N load level, significant differences between the models were found. Both models accurately predicted the creep response under the first 800 s of 100 N loading, as displayed by mean absolute errors for the calculated deformation data from the experimental data of 1.26 and 0.97 percent for the solid and fluid models respectively. The linear Burger's fluid model, however, yielded superior predictions particularly for the initial elastic response.
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| 7. |
- Gorski, Mathias, et al.
(författare)
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Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
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Tidskriftsartikel (refereegranskat)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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| 8. |
- Grövdal, Michael, et al.
(författare)
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Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy
- 2010
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 150:3, s. 293-302
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Tidskriftsartikel (refereegranskat)abstract
- This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction chemotherapy. Sixty patients were enrolled and treated by standard induction chemotherapy. Patients that reached CR started maintenance therapy with subcutaneous azacytidine, 5/28 d until relapse. Promoter-methylation status of CDKN2B (P15 ink4b), CDH1 and HIC1 was examined pre-induction, in CR and 6, 12 and 24 months post CR. Twenty-four (40%) patients achieved CR after induction chemotherapy and 23 started maintenance treatment with azacytidine. Median CR duration was 13.5 months, >24 months in 17% of the patients, and 18-30.5 months in the four patients with trisomy 8. CR duration was not associated with CDKN2B methylation status or karyotype. Median overall survival was 20 months. Hypermethylation of CDH1 was significantly associated with low CR rate, early relapse, and short overall survival (P = 0.003). 5-azacytidine treatment, at a dose of 60 mg/m(2) was well tolerated. Grade III-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients.
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| 9. |
- Henriksnäs, Johanna, 1973-
(författare)
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Helicobacter pylori and Gastric Protection Mechanisms : An in vivo Study in Mice and Rats
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The stomach is frequently exposed to hazardous agents and to resist this harsh environment, several protective mechanisms exist. Of special interest is the gastric pathogen Helicobacter pylori which causes gastritis, ulcers and cancer but the mechanism leading to these diseases are still unclear. However it is very likely that H. pylori negatively influence the protection mechanisms that exist in the stomach. The aims of the present investigation were first to develop an in vivo mouse model in which different protection mechanisms could be studied, and second to investigate the influence of H. pylori on these mechanisms. An in vivo preparation of the gastric mucosa in mice was developed. This preparation allows studies of different gastric mucosal variables and can also be applied for studies in other gastro-intestinal organs. Mice chronically infected with H. pylori, were shown to have a reduced ability of the mucosa to maintain a neutral pH at the epithelial cell surface. This could be due to the thinner inner, firmly adherent mucus gel layer, and/or to defective bicarbonate transport across the epithelium. The Cl-/HCO3- exchanger SLC26A9 was inhibited by NH4+, which also is produced by H. pylori. The mRNA levels of SLC26A9 were upregulated in infected mice, suggesting a way to overcome the inhibition of the transporter. Furthermore, the hyperemic response to acid pH 2 and 1.5 was abolished in these mice. The mechanisms by which the bacteria could alter the blood flow response might involve inhibition of the epithelial iNOS.Water extracts of H. pylori (HPE) reduces the blood flow acutely through an iNOS and nerve-mediated pathway, possibly through the endogenous iNOS inhibitor ADMA. Furthermore, HPE alters the blood flow response to acid as the hyperemic response to acid pH 0.8 is accentuated in mice treated with HPE.
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| 10. |
- Hodges, Paul, et al.
(författare)
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Intervertebral stiffness of the spine is increased by evoked contraction of transversus abdominis and the diaphragm : in vivo porcine studies.
- 2003
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Ingår i: Spine. - 1528-1159. ; 28:23, s. 2594-601
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN: In vivo porcine study of intervertebral kinematics. OBJECTIVES: This study investigated the effect of transversus abdominis and diaphragm activity, and increased intra-abdominal pressure on intervertebral kinematics in porcine lumbar spines. BACKGROUND: Studies of trunk muscle recruitment in humans suggest that diaphragm and transversus abdominis activity, and the associated intra-abdominal pressure contribute to the control of intervertebral motion. However, this has not been tested in vivo. METHODS: Relative intervertebral motion of the L3 and L4 vertebrae and the stiffness at L4 were measured in response to displacements of the L4 vertebra imposed via a device fixed to the L4 vertebral body. In separate trials, diaphragm and transversus abdominis activity was evoked by stimulation of the phrenic nerves and via electrodes threaded through the abdominal wall. RESULTS: When intra-abdominal pressure was increased by diaphragm or transversus abdominis stimulation, the relative intervertebral displacement of the L3 and L4 vertebrae was reduced and the stiffness of L4 was increased for caudal displacements. There was no change in either parameter for rostral displacements. In separate trials, the diaphragm crurae and the fascial attachments of transversus abdominis were cut, but intra-abdominal pressure was increased. In these trials, the reduction in intervertebral motion was similar to trials with intact attachments for caudal motion, but was increased for rostral trials. CONCLUSIONS: The results of these studies indicate that elevated intra-abdominal pressure, and contraction of diaphragm and transversus abdominis provide a mechanical contribution to the control of spinal intervertebral stiffness. Furthermore, the effect is modified by the muscular attachments to the spine.
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