| 1. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 2. |
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| 3. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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| 4. |
- Aspenberg, Per, et al.
(författare)
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Targeting RANKL for reduction of bone loss around unstable implants: OPG-Fc compared to alendronate in a model for mechanically induced loosening
- 2011
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Ingår i: BONE. - : Elsevier Science B.V., Amsterdam.. - 8756-3282. ; 48:2, s. 225-230
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Tidskriftsartikel (refereegranskat)abstract
- Orthopedic joint prostheses may loosen because of localized bone resorption. Despite initial optimism, there are no reports showing that bisphosphonates can stop the progression of prosthetic loosening once it has begun. This might be due to the strong resorptive stimulus, which continuously recruits new osteoclasts. Therefore, we hypothesized that a treatment targeting osteoclast recruitment would be more efficacious than a treatment reducing osteoclast activity. We used a previously described rat model for instability-induced bone resorption, and compared OPG-Fc with alendronate at a clinically relevant or an extreme dose. A titanium plate was osseointegrated at the rat tibial surface. Instability was simulated by a piston, moving perpendicularly to the bone surface. Piston movement induced bone loss via hydrostatic pressure or fluid flow. Rats were randomized to 5 groups (total n = 56), of which 4 were subjected to instability and one was stable. The unstable groups were injected with either high-dose OPG-Fc (10 mg/kg, twice weekly), a high dose of alendronate (20 mu g /kg/day), an extreme dose of alendronate (200 mu g/kg/day) or saline. Significant protection against resorption could only be shown for OPG-Fc and the extreme alendronate dose. Both alendronate doses reduced serum levels of tartrate-resistant acid phosphatase isoform 5b to a similar extent, demonstrating that the lower dose was able to reduce resorption in the normally remodeling skeleton, although not in the osteolytic lesions caused by instability. Osteoclast numbers in the lesion were increased by the lower bisphosphonate dose and reduced by OPG-Fc. The results suggest the possibility of targeting osteoclast recruitment via the RANKL system in patients with impending prosthetic loosening.
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| 5. |
- Blomberg, Per, 1969-, et al.
(författare)
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Längdskala i visuell programmeringsmiljö : Learning Study på mellanstadiet
- 2019
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Ingår i: Syntes 2019. - : Kommunförbundet Skåne. ; , s. 14-26
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Konferensbidrag (refereegranskat)abstract
- Denna Learning study, genomförd på en mellanstadieskola i en medelstor kommun, fokuserar på kritiska aspekter som framkommer då elever lär längdskala och hur elever ges möjlighet att urskilja dessa kritiska aspekter i undervisning. Studien har avgränsats till hur skala kan introduceras och därefter vida- reutvecklas i en visuell programmeringsmiljö. Närmare bestämt betraktas dels innebörden av skrivsät- tet för längdskala, dels övergången från en- till tvådimensionell figur. Studiens huvudresultat pekarpå vikten av att noggrant introducera skala genom att koppla skrivsätten a:1 och 1:b till motsvarande bråkform a/1 och 1/b. Därigenom erbjuds elever möjligheten att erfara proportionellt tänkande och multiplikativa processer. Studien fann även att visuell programmeringsmiljö har potential att användas i undervisning för att variera och urskilja förstoring och förminskning av tvådimensionella figurer.
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| 6. |
- Diaz, Sandra, et al.
(författare)
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Hyperpolarized (3)He apparent diffusion coefficient MRI of the lung: Reproducibility and volume dependency in healthy volunteers and patients with emphysema.
- 2008
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Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley. - 1522-2586 .- 1053-1807. ; 27, s. 763-770
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To measure the apparent diffusion coefficient (ADC) of hyperpolarized (HP) (3)He gas using diffusion weighted MRI in healthy volunteers and patients with emphysema and examine the reproducibility and volume dependency. MATERIALS AND METHODS: A total of eight healthy volunteers and 16 patients with emphysema were examined after inhalation of HP (3)He gas mixed with nitrogen (N(2)) during breathhold starting from functional residual capacity (FRC) in supine position. Coronal diffusion-sensitized MR images were acquired. Each subject was imaged on three separate days over a seven-day period and received two different volumes (6% and 15% of total lung capacity [TLC]) of HP (3)He each day. ADC maps and histograms were calculated. The mean and standard deviation (SD) of the ADC at different days and volumes were compared. RESULTS: The reproducibility of the mean ADC and SD over several days was good in both healthy volunteers and patients (SD range of 0.003-0.013 cm(2)/second and 0.001-0.009 cm(2)/second at 6% and 15% of TLC for healthy volunteers, and a SD range of 0.001-0.041 cm(2)/second and 0.001-0.011 cm(2)/second, respectively, for patients). A minor but significant increase in mean ADC with increased inhaled gas volume was observed in both groups. CONCLUSION: Mean ADC and SD of HP (3)He MRI is reproducible and discriminates well between healthy controls and patients with emphysema at the higher gas volume. This method is robust and may be useful to gain new insights into the pathophysiology and course of emphysema. J. Magn. Reson. Imaging 2008. (c) 2008 Wiley-Liss, Inc.
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| 7. |
- Diaz, Sandra, et al.
(författare)
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Validity of apparent diffusion coefficient hyperpolarized He-3-MRI using MSCT and pulmonary function tests as references
- 2009
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Ingår i: European Journal of Radiology. - : Elsevier BV. - 1872-7727 .- 0720-048X. ; 71:2, s. 257-263
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To compare apparent diffusion coefficient (ADC) measurements from hyperpolarized (HP) helium (He-3)-magnetic resonance imaging (MRI) with quantitative data from multislice Computed Tomography (CT) (MSCT) of the whole lungs and pulmonary function tests (PFT). Materials and methods: Twenty-seven subjects, 22 with established emphysema and 5 with preclinical emphysema defined by PFT criteria, were examined with Hp He-3-MRI and MSCT. Mean age was 55 (+/- 12) years, 18 female and 9 male. Mean ADC from He-3-MRI was compared with emphysema index (EI), 15th percentile and mean lung density (MLD) values from MSCT. Both mean ADC and MSCT data were compared to PFT, especially percent of predicted diffusing capacity of carbon monoxide (%predicted DLCO), using Pearson's correlation test. Results: Mean ADC and standard deviation values were 0.392 +/- 0.119 cm(2)/s for the established emphysema group and 0.216 +/- 0.046 for the pre-clinical emphysema group. MSCT values for the established emphysema group and pre-clinical emphysema group were: EI (%) 11 +/- 12 and 0.4 +/- 0.6, respectively; 15th percentile (Hounsfield Units (HU)), -956 +/- 25 and -933 +/- 13, respectively and MLD (HU) -877 +/- 20 and -863 +/- 15, respectively. Correlations between mean ADC and El and 15th percentile were both r=0.90 and for MLD r=0.59. There was higher correlation between mean ADC and %predicted DLCO (r=0.90) than between El and %predicted DLCO (r=0.76). Conclusion: Hp He-3-MRI correlates well with density measurements from MSCT and agrees better than MSCT with %predicted DLCO which is the PFT most related to emphysema. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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| 8. |
- Engelmark, Malin, et al.
(författare)
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Polymorphisms in 9q32 and TSCOT are linked to cervical cancer in affected sib-pairs with high mean age at diagnosis
- 2008
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 123:5, s. 437-443
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Tidskriftsartikel (refereegranskat)abstract
- Cervical cancer is a multifactorial disease influenced by both environmental and genetic factors. We have previously found linkage to 9q32 in a genomewide scan of affected sib-pairs (ASPs) with cervical cancer and to the thymic stromal co-transporter (TSCOT), a candidate gene in this region. Here we examined the contribution of 9q32 and TSCOT to cervical cancer susceptibility using at larger material of 641 ASPs, 278 of which were included in the earlier genome-scan. Since heritable forms of cancer frequently show stronger genetic effects in families with early onset of disease, we stratified the ASPs into two groups based on mean age at diagnosis (MAAD) within sib-pairs. Surprisingly, ASPs with high MAAD (30.5-47.5 years) showed increased sharing at all microsatellite markers at 9q31.1-33.1 and linkage signals of up to MLS = 2.74 for TSCOT SNPs, while ASPs with low MAAD (19-30 years) showed no deviation from random genetic sharing (MLS = 0.00). The difference in allelic sharing between the two MAAD strata was significant (P < 0.005) and is not likely to be explained by the HLA haplotype, a previously known genetic susceptibility factor for cervical cancer. Our results indicate locus heterogeneity in the susceptibility to cervical cancer between the two strata, with polymorphisms in the 9q32 region mainly showing an effect in women with high MAAD.
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| 10. |
- Gretarsdottir, Solveig, et al.
(författare)
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Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:8, s. 71-692
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Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.
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