| 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. |
- Adams, Yvonne, et al.
(författare)
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3D blood-brain barrier-organoids as a model for Lyme neuroborreliosis highlighting genospecies dependent organotropism
- 2023
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Ingår i: ISCIENCE. - : CELL PRESS. - 2589-0042. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Lyme neuroborreliosis (LNB), a tick-borne infection caused by spirochetes within the Borrelia burgdorferi sensu lato (s.L.) complex, is among the most prevalent bacterial central nervous system (CNS) infections in Europe and the US. Here we have screened a panel of low- passage B. burgdorferi s.l. isolates using a novel, human-derived 3D blood-brain barrier (BBB)-organoid model. We show that human-derived BBB-organoids support the entry of Borrelia spirochetes, leading to swelling of the organoids and a loss of their structural integrity. The use of the BBB-organoid model highlights the organotropism between B. burgdorferi s.l. genospecies and their ability to cross the BBB contributing to CNS infection.
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| 3. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 4. |
- Allentoft, Morten E., et al.
(författare)
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100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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| 5. |
- Arnlund, David, et al.
(författare)
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Visualizing a protein quake with time-resolved X-ray scattering at a free-electron laser
- 2014
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Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 11:9, s. 923-926
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Tidskriftsartikel (refereegranskat)abstract
- We describe a method to measure ultrafast protein structural changes using time-resolved wide-angle X-ray scattering at an X-ray free-electron laser. We demonstrated this approach using multiphoton excitation of the Blastochloris viridis photosynthetic reaction center, observing an ultrafast global conformational change that arises within picoseconds and precedes the propagation of heat through the protein. This provides direct structural evidence for a 'protein quake': the hypothesis that proteins rapidly dissipate energy through quake-like structural motions.
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| 6. |
- Capo, Eric, et al.
(författare)
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Lake sedimentary dna research on past terrestrial and aquatic biodiversity: Overview and recommendations
- 2021
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Ingår i: Quaternary. - : MDPI. - 2571-550X. ; 4:1
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Forskningsöversikt (refereegranskat)abstract
- The use of lake sedimentary DNA to track the long-term changes in both terrestrial and aquatic biota is a rapidly advancing field in paleoecological research. Although largely applied nowadays, knowledge gaps remain in this field and there is therefore still research to be conducted to ensure the reliability of the sedimentary DNA signal. Building on the most recent literature and seven original case studies, we synthesize the state-of-the-art analytical procedures for effective sampling, extraction, amplification, quantification and/or generation of DNA inventories from sedimentary ancient DNA (sedaDNA) via high-throughput sequencing technologies. We provide recommendations based on current knowledge and best practises.
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| 7. |
- Fransson, Claes, et al.
(författare)
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Late spectral evolution of the ejecta and reverse shock in SN 1987a
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 768:1, s. 88-
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Tidskriftsartikel (refereegranskat)abstract
- We present observations with the Very Large Telescope and Hubble Space Telescope (HST) of the broad emission lines from the inner ejecta and reverse shock of SN 1987A from 1999 February until 2012 January (days 4381-9100 after explosion). We detect broad lines from H alpha, H beta, Mg I], Na I, [O I], [Ca II], and a feature at similar to 9220 angstrom. We identify the latter line with Mg II lambda lambda 9218, 9244, which is most likely pumped by Ly alpha fluorescence. H alpha and H beta both have a centrally peaked component extending to similar to 4500 km s(-1) and a very broad component extending to greater than or similar to 11,000 km s(-1), while the other lines have only the central component. The low-velocity component comes from unshocked ejecta, heated mainly by X-rays from the circumstellar environment, whereas the very broad component comes from faster ejecta passing through the reverse shock, created by the collision with the circumstellar ring. The flux in H alpha from the reverse shock has increased by a factor of four to six from 2000 to 2007. After that there is a tendency of flattening of the light curve, similar to what may be seen in the optical lines from the shocked ring. The core component seen in H alpha, [Ca II], and Mg II has experienced a similar increase, which is consistent with that found from HST photometry. The energy deposition of the external X-rays is calculated using explosion models for SN 1987A and we predict that the outer parts of the unshocked ejecta will continue to brighten because of this. The external X-ray illumination also explains the edge-brightened morphology of the ejecta seen in the HST images. We finally discuss evidence for dust in the ejecta from line asymmetries.
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| 8. |
- Georg, Dietmar, et al.
(författare)
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Clinical evaluation of monitor unit software and the application of action levels
- 2007
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 85:2, s. 306-315
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was the clinical evaluation of an independent dose and monitor unit verification (MUV) software which is based on sophisticated semi-analytical modelling. The software was developed within the framework of an ESTRO project. Finally, consistent handling of dose calculation deviations applying individual action levels is discussed. MATERIALS AND METHODS: A Matlab-based software ("MUV") was distributed to five well-established treatment centres in Europe (Vienna, Graz, Basel, Copenhagen, and Umeå) and evaluated as a quality assurance (QA) tool in clinical routine. Results were acquired for 226 individual treatment plans including a total of 815 radiation fields. About 150 beam verification measurements were performed for a portion of the individual treatment plans, mainly with time variable fluence patterns. The deviations between dose calculations performed with a treatment planning system (TPS) and the MUV software were scored with respect to treatment area, treatment technique, geometrical depth, radiological depth, etc. RESULTS: In general good agreement was found between calculations performed with the different TPSs and MUV, with a mean deviation per field of 0.2+/-3.5% (1 SD) and mean deviations of 0.2+/-2.2% for composite treatment plans. For pelvic treatments less than 10% of all fields showed deviations larger than 3%. In general, when using the radiological depth for verification calculations the results and the spread in the results improved significantly, especially for head-and-neck and for thorax treatments. For IMRT head-and-neck beams, mean deviations between MUV and the local TPS were -1.0+/-7.3% for dynamic, and -1.3+/-3.2% for step-and-shoot IMRT delivery. For dynamic IMRT beams in the pelvis good agreement was obtained between MUV and the local TPS (mean: -1.6+/-1.5%). Treatment site and treatment technique dependent action levels between +/-3% and +/-5% seem to be clinically realistic if a radiological depth correction is performed, even for dynamic wedges and IMRT. CONCLUSION: The software MUV is well suited for patient specific treatment plan QA applications and can handle all currently available treatment techniques that can be applied with standard linear accelerators. The highly sophisticated dose calculation model implemented in MUV allows investigation of systematic TPS deviations by performing calculations in homogeneous conditions
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| 9. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 10. |
- Kjær, Lene Jung, et al.
(författare)
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Potential drivers of human tick-borne encephalitis in the Örebro region of Sweden, 2010-2021
- 2023
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Incidence of tick-borne encephalitis (TBE) has increased during the last years in Scandinavia, but the underlying mechanism is not understood. TBE human case data reported between 2010 and 2021 were aggregated into postal codes within Örebro County, south-central Sweden, along with tick abundance and environmental data to analyse spatial patterns and identify drivers of TBE. We identified a substantial and continuing increase of TBE incidence in Örebro County during the study period. Spatial cluster analyses showed significant hotspots (higher number of cases than expected) in the southern and northern parts of Örebro County, whereas a cold spot (lower number of cases than expected) was found in the central part comprising Örebro municipality. Generalised linear models showed that the risk of acquiring TBE increased by 12.5% and 72.3% for every percent increase in relative humidity and proportion of wetland forest, respectively, whereas the risk decreased by 52.8% for every degree Celsius increase in annual temperature range. However, models had relatively low goodness of fit (R2 < 0.27). Results suggest that TBE in Örebro County is spatially clustered, however variables used in this study, i.e., climatic variables, forest cover, water, tick abundance, sheep as indicator species, alone do not explain this pattern.
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| 11. |
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| 12. |
- Lu, Yingchang, et al.
(författare)
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A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk.
- 2018
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 78:18, s. 5419-5430
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Tidskriftsartikel (refereegranskat)abstract
- .AbstractLarge-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 × 10−6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10−7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 × 10−3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis.Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419–30. ©2018 AACR.
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| 13. |
- Ahlgren, Madeleine, 1976-, et al.
(författare)
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Self-reported symptoms of low energy availability among female elite athletes and controls
- 2023
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Konferensbidrag (refereegranskat)abstract
- AimWe aimed to investigate symptoms of low energy availability (LEA) among athletes and recreational active people, and the associations with EDs, excessive exercise, and motivation for training and dietary behavioural changes. MethodsSwedish female national team athletes (n=150) from 26 sports, and recreational active women (n=108), 18-39 years were recruited via sport organizations and social media. Participants filled out an anonymous on-line survey comprising the LEA in Females Questionnaire (LEAF-Q), the Eating Disorder Examination Questionnaire (EDE-Q), the Major Depression Index (MDI), the Exercise Addiction Inventory (EAI), and the Motivation to Change Questionnaire (MCQ). LEAF-Q total score >8 and EDE-Q Global score >2.3 were used to classify participants as having symptoms of LEA and eating disorders (EDs), respectively.ResultsOf all participants, 47% had symptoms of LEA with no difference between elite athletes (47%) and controls (48%). Participants with LEA had lower body mass and BMI compared to those with no symptoms, while no differences were found in age or training load. Most of the participants with LEA (69%) did not have symptoms of EDs. However, when excluding all participants with ED symptoms (n=65), participants with LEA had higher EDE-Q sub scale scores, MDI and EAI scores, and they reported poorer health status and reduced ability to increase energy intake and to lower the training load compared to participants with no LEA symptoms. ConclusionOur findings confirm earlier indications that symptoms of LEA is frequent among elite athletes as well as sedentary people, and that most LEA cases do not have EDs. However, our findings suggest that symptoms of LEA may still be associated with poor well-being, restricted eating and excessive training behaviour and negative focus on body shape and weight. Reversing LEA by increased energy intake and/or reduced training load is the only treatment to prevent REDs health and performance implications. Our findings therefore emphasize the need for multidisciplinary prevention strategies to ensure necessary dietary and training behavioural changes.
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| 14. |
- Ambrosini, Valentina, et al.
(författare)
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Use and perceived utility of [18 F]FDG PET/CT in neuroendocrine neoplasms : A consensus report from the European Neuroendocrine Tumor Society (ENETS) Advisory Board Meeting 2022.
- 2024
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Ingår i: Journal of neuroendocrinology. - 0953-8194 .- 1365-2826. ; 36:1, s. e13359-
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Tidskriftsartikel (refereegranskat)abstract
- Somatostatin receptor (SST) PET/CT is the gold standard for well-differentiated neuroendocrine tumours (NET) imaging. Higher grades of neuroendocrine neoplasms (NEN) show preferential [18F]FDG (FDG) uptake, and even low-grade NET may de-differentiate over time. FDG PET/CT's prognostic role is widely accepted; however, its impact on clinical decision-making remains controversial and its use varies widely. A questionnaire-based survey on FDG PET/CT use and perceived decision-making utility in NEN was submitted to the ENETS Advisory Board Meeting attendees (November 2022, response rate = 70%). In 3/15 statements, agreement was higher than 75%: (i) FDG was considered useful in NET, irrespective of grade, in case of mis-matched lesions (detectable on diagnostic CT but negative/faintly positive on SST PET/CT), especially if PRRT is contemplated (80%); (ii) in NET G3 if curative surgery is considered (82%); and (iii) in NEC prior to surgery with curative intent (98%). FDG use in NET G3, even in the presence of matched lesions, as a baseline for response assessment was favoured by 74%. Four statements obtained more than 60% consensus: (i) FDG use in NET G3 if locoregional therapy is considered (65%); (ii) in neuroendocrine carcinoma before initiating active therapy as a baseline for response assessment (61%); (iii) biopsy to re-assess tumour grade prior to a change in therapeutic management (68%) upon detection of FDG-positivity on the background of a prior G1-2 NET; (iv) 67% were in favour to reconsider PRRT to treat residual SST-positive lesions after achieving complete remission on FDG of the SST-negative disease component. Multidisciplinary opinion broadly supports the use of FDG PET/CT for characterisation of disease biology and to guide treatment selection across a range of indications, despite the lack of full consensus in many situations. This may reflect existing clinical access due to lack of reimbursement or experience with this investigation, which should be addressed by further research.
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| 15. |
- Biasin, Elisa, et al.
(författare)
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Anisotropy enhanced X-ray scattering from solvated transition metal complexes
- 2018
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Ingår i: Journal of Synchrotron Radiation. - 0909-0495. ; 25:2, s. 306-315
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Tidskriftsartikel (refereegranskat)abstract
- Time-resolved X-ray scattering patterns from photoexcited molecules in solution are in many cases anisotropic at the ultrafast time scales accessible at X-ray free-electron lasers (XFELs). This anisotropy arises from the interaction of a linearly polarized UV-Vis pump laser pulse with the sample, which induces anisotropic structural changes that can be captured by femtosecond X-ray pulses. In this work, a method for quantitative analysis of the anisotropic scattering signal arising from an ensemble of molecules is described, and it is demonstrated how its use can enhance the structural sensitivity of the time-resolved X-ray scattering experiment. This method is applied on time-resolved X-ray scattering patterns measured upon photoexcitation of a solvated di-platinum complex at an XFEL, and the key parameters involved are explored. It is shown that a combined analysis of the anisotropic and isotropic difference scattering signals in this experiment allows a more precise determination of the main photoinduced structural change in the solute, i.e. the change in Pt - Pt bond length, and yields more information on the excitation channels than the analysis of the isotropic scattering only. Finally, it is discussed how the anisotropic transient response of the solvent can enable the determination of key experimental parameters such as the instrument response function.The analysis of time-resolved X-ray scattering patterns collected at an XFEL upon photoexcitation of a di-platinum complex in solution is described. The analysis quantitatively considers the anisotropy of the signal.
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| 16. |
- Bojsen-Møller, Jens, et al.
(författare)
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Differential displacement of the human soleus and medial gastrocnemius aponeuroses during isometric plantar flexor contractions in vivo.
- 2004
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Ingår i: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 97:5, s. 1908-14
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Tidskriftsartikel (refereegranskat)abstract
- The human triceps surae muscle-tendon complex is a unique structure with three separate muscle compartments that merge via their aponeuroses into the Achilles tendon. The mechanical function and properties of these structures during muscular contraction are not well understood. The purpose of the study was to investigate the extent to which differential displacement occurs between the aponeuroses of the medial gastrocnemius (MG) and soleus (Sol) muscles during plantar flexion. Eight subjects (mean +/- SD; age 30 +/- 7 yr, body mass 76.8 +/- 5.5 kg, height 1.83 +/- 0.06 m) performed maximal isometric ramp contractions with the plantar flexor muscles. The experiment was performed in two positions: position 1, in which the knee joint was maximally extended, and position 2, in which the knee joint was maximally flexed (125 degrees ). Plantarflexion moment was assessed with a strain gauge load cell, and the corresponding displacement of the MG and Sol aponeuroses was measured by ultrasonography. Differential shear displacement of the aponeurosis was quantified by subtracting displacement of Sol from that of MG. Maximal plantar flexion moment was 36% greater in position 1 than in position 2 (132 +/- 20 vs. 97 +/- 11 N.m). In position 1, the displacement of the MG aponeurosis at maximal force exceeded that of the Sol (12.6 +/- 1.7 vs. 8.9 +/- 1.5 mm), whereas in position 2 displacement of the Sol was greater than displacement of the MG (9.6 +/- 1.0 vs. 7.9 +/- 1.2 mm). The amount and "direction" of shear between the aponeuroses differed significantly between the two positions across the entire range of contraction, indicating that the Achilles tendon may be exposed to intratendinous shear and stress gradients during human locomotion.
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| 17. |
- Bolin, Kristian, et al.
(författare)
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Characteristics of finasteride users in comparison with non-users: a Nordic nationwide study based on individual-level data from Denmark, Finland, and Sweden
- 2020
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Ingår i: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 29:4, s. 453-460
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Published epidemiological studies on the association between finasterideuse and the risk of male breast cancer have been inconclusive due to methodologicallimitations including a few male breast cancer cases included. Determinants of malebreast cancer have been studied, but it remains unexplored whether these are alsorelated to finasteride use and thereby constitute potential confounders. This studyaimed to assess whether there are differences between finasteride users andnonusers with regard to numerous potential confounders.Methods: In total, 246 508 finasteride users (≥35 years) were identified in the pre-scription registries of Denmark (1995-2014), Finland (1997-2013), and Sweden(2005-2014). An equal number of nonusers were sampled. The directed acyclic graph(DAG) methodology was used to identify potential confounders for the associationbetween finasteride and male breast cancer. A logistic regression model comparedfinasteride users and nonusers with regard to potential confounders that were mea-surable in registries and population surveys.Results: Finasteride users had higher odds of testicular abnormalities (odds ratio[OR] 1.40; 95% confidence interval [CI] 1.36-1.44), obesity (1.31; 1.23-1.39), exoge-nous testosterone (1.61; 1.48-1.74), radiation exposure (1.22; 1.18-1.27), and diabe-tes (1.07; 1.04-1.10) and lower odds of occupational exposure in perfume industry orin high temperature environments (0.93; 0.87-0.99), living alone (0.89; 0.88-0.91), liv-ing in urban/suburban areas (0.97; 0.95-0.99), and physical inactivity (0.70;0.50-0.99) compared to nonusers.Conclusions: Systematic differences between finasteride users and nonusers werefound emphasizing the importance of confounder adjustment of associationsbetween finasteride and male breast cancer.
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| 18. |
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| 19. |
- Ekbäck, Peter, 1961-, et al.
(författare)
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Road Management in Denmark and Sweden : A Comparison and Analysis of Institutional Designs
- 2020
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Ingår i: Nordic Journal of Surveying and Real Estate Research. - : Nordic Journal of Surveying and Real Estate Research. - 1459-5877 .- 2341-6599. ; 15:1, s. 38-55
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Tidskriftsartikel (refereegranskat)abstract
- Management of roads and the institutional solution chosen is dependent on a number of factors such as, regulatory tradition, and roadnetwork scale. It is likely that some solutions are more efficient than others,and this article compares and analyses Danish and Swedish institutional solutions regarding road management. The aim is to explore and briefly evaluate the systems in terms of institutional efficiency. The hypothesis is that, efficient institutions have a better ability for survival in the politicalprocesses. It is observed that the chosen solutions on national and municipallevel are much alike, and therefore appear efficient. However, for common private roads, the institutional designs are very different, and seem to bebased on two diametrically contrasting views on how to govern this kind of roads.
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| 20. |
- Elam, Cecilia, et al.
(författare)
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Effects of age on muscle power, postural control and functional capacity after short-term immobilization and retraining.
- 2022
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Ingår i: Journal of musculoskeletal & neuronal interactions. - 1108-7161. ; 22:4, s. 486-497
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the effect of lower limb immobilization and retraining on postural control and muscle power in healthy old and young men.Twenty men, nine old (OM:67.3±4.4 years) and eleven young (YM:24.4±1.6 years) underwent 2 weeks of unilateral whole-leg casting, followed by 4 weeks of retraining. Measures included center of pressure (CoP) sway length and area during single- and double-leg stance, maximal leg extensor muscle power, habitual and maximal 10-m gait speed, sit-to-stand performance, and 2-min step test.After immobilization, leg extension muscle power decreased by 15% in OM (from 2.68±0.60 to 2.29±0.63 W/kg, p<0.05) and 17% in YM (4.37±0.76 to 3.63±0.69 W/kg, p<0.05). Double-leg CoP sway area increased by 45% in OM (218±82 to 317±145 mm2; p<0.05), with no change in YM (p=0.43). Physical function did not change after immobilization but sit-to-stand performance (+20%, p<0.05) and 2-min step test (+28%, p<0.05) increased in OM following retraining. In both groups, all parameters returned to baseline levels after retraining.Two weeks of lower limb immobilization led to decreases in maximal muscle power in both young and old, whereas postural control was impaired selectively in old men. All parameters were restored in both groups after 4 weeks of resistance-based retraining.
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| 21. |
- Eliasson, Pernilla, 1982-, et al.
(författare)
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Simvastatin and atorvastatin reduce the mechanical properties of tendon constructs in vitro and introduce catabolic changes in the gene expression pattern
- 2017
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with lipid-lowering drugs, statins, is common all over the world. Lately, the occurrence of spontaneous tendon ruptures or tendinosis have suggested a negative influence of statins upon tendon tissue. But how statins might influence tendons is not clear. In the present study, we investigated the effect of statin treatment on mechanical strength, cell proliferation, collagen content and gene expression pattern in a tendon-like tissue made from human tenocytes in vitro. Human tendon fibroblasts were grown in a 3D tissue culture model (tendon constructs), and treated with either simvastatin or atorvastatin, low or high dose, respectively, for up to seven days. After seven days of treatment, mechanical testing of the constructs was performed. Collagen content and cell proliferation were also determined. mRNA levels of several target genes were measured after one or seven days. The maximum force and stiffness were reduced by both statins after 7 days (pamp;lt;0.05), while the cross sectional area was unaffected. Further, the collagen content was reduced by atorvastatin (p = 0.01) and the cell proliferation rate was decreased by both types of statins (pamp;lt;0.05). Statin treatment also introduced increased mRNA levels of MMP-1, MMP-3, MMP-13, TIMP-1 and decreased levels of collagen type 1 and 3. In conclusion, statin treatment appears to have a negative effect on tendon matrix quality as seen by a reduced strength of the tendon constructs. Further, activated catabolic changes in the gene expression pattern and a reduced collagen content indicated a disturbed balance in matrix production of tendon due to statin administration.
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| 22. |
- Eliasson, Pernilla T., et al.
(författare)
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The Ruptured Achilles Tendon Elongates for 6 Months After Surgical Repair Regardless of Early or Late Weightbearing in Combination With Ankle Mobilization: A Randomized Clinical Trial
- 2018
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Ingår i: American Journal of Sports Medicine. - : SAGE PUBLICATIONS INC. - 0363-5465 .- 1552-3365. ; 46:10, s. 2492-2502
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Tidskriftsartikel (refereegranskat)abstract
- Background: Treatment strategies for Achilles tendon rupture vary considerably, and clinical outcome may depend on the magnitude of tendon elongation after surgical repair. The aim of this project was to examine whether tendon elongation, mechanical properties, and functional outcomes during rehabilitation of surgically repaired acute Achilles tendon ruptures were influenced by different rehabilitation regimens during the early postsurgical period. Hypothesis: Restricted early weightbearing that permits only limited motion about the ankle in the early phase of tendon healing limits tendon elongation and improves functional outcome. Study Design:Randomized controlled trial; Level of evidence, 1. Methods: 75 consecutive patients with an acute Achilles tendon rupture were included. They underwent surgical repair, and tantalum beads were placed in the distal and proximal parts of the tendon; thereafter, the patients were randomized into 3 groups. The first group was completely restricted from weightbearing until week 7. The second group was completely restricted from weightbearing until week 7 but performed ankle joint mobilization exercises. The first and second groups were allowed full weightbearing after week 8. The third group was allowed partial weightbearing from day 1 and full weightbearing from week 5. All patients received the same instructions in home exercise guidelines starting from week 9. Results: The rehabilitation regimen in the initial 8 weeks did not significantly influence any of the measured outcomes including tendon elongation. Achilles tendon elongation and tendon compliance continued for up to 6 months after surgery, and muscle strength, muscle endurance, and patient-reported functional scores did not reach normal values at 12 months. Conclusion: Differences in rehabilitation loading pattern in the initial 8 weeks after the repair of an Achilles tendon rupture did not measurably alter the outcome. The time to recover full function after an Achilles tendon rupture is at least 12 months.
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| 23. |
- Gronbaek, Jonathan Kjaer, et al.
(författare)
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Left-handedness should not be overrated as a risk factor for postoperative speech impairment in children after posterior fossa tumour surgery : a prospective European multicentre study
- 2022
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Ingår i: Child's Nervous System. - : Springer Nature. - 0256-7040 .- 1433-0350. ; 38:8, s. 1479-1485
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Cerebellar mutism syndrome (CMS) is a severe neurological complication of posterior fossa tumour surgery in children, and postoperative speech impairment (POSI) is the main component. Left-handedness was previously suggested as a strong risk factor for POSI. The aim of this study was to investigate the relationship between handedness and the risk of POSI. Methods We prospectively included children (aged < 18 years) undergoing surgery for posterior fossa tumours in 26 European centres. Handedness was assessed pre-operatively and postoperative speech status was categorised as either POSI (mutism or reduced speech) or habitual speech, based on the postoperative clinical assessment. Logistic regression was used in the risk factor analysis of POSI as a dichotomous outcome. Results Of the 500 children included, 37 (7%) were excluded from the present analysis due to enrolment at a reoperation; another 213 (43%) due to missing data about surgery (n = 37) and/or handedness (n = 146) and/or postoperative speech status (n = 53). Out of the remaining 250 (50%) patients, 20 (8%) were left-handed and 230 (92%) were right-handed. POSI was observed equally frequently regardless of handedness (5/20 [25%] in left-handed, 61/230 [27%] in right-handed, OR: 1.08 [95% CI: 0.40-3.44], p = 0.882), also when adjusted for tumour histology, location and age. Conclusion We found no difference in the risk of POSI associated with handedness. Our data do not support the hypothesis that handedness should be of clinical relevance in the risk assessment of CMS.
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| 24. |
- Gröningsson, Per, et al.
(författare)
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High resolution spectroscopy of the inner ring of SN 1987A
- 2008
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 479:3, s. 761-777
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Tidskriftsartikel (refereegranskat)abstract
- We discuss high resolution VLT/UVES observations (FWHM similar to 6 kms(-1)) from October 2002 (day similar to 5700 past explosion) of the shock interaction of SN 1987A and its circumstellar ring. A large number of narrow emission lines from the unshocked ring, with ion stages from neutral up to Ne V and Fe VII, have been identified. A nebular analysis of the narrow lines from the unshocked gas indicates gas densities of (similar to 1.5 - 5.0) x 10(3) cm(-3) and temperatures of similar to 6.5 x 10(3) - 2.4 x 104 K. This is consistent with the thermal widths of the lines. From the shocked component we observe a large range of ionization stages from neutral lines to [FeXIV]. From a nebular analysis we find that the density in the low ionization region is 4 x 10(6) - 10(7) cm-3. There is a clear difference in the high velocity extension of the low ionization lines and that of lines from [Fe X - XIV], with the latter extending up to similar to- 390 km s(-1) in the blue wing for [Fe XIV], while the low ionization lines extend to typically similar to- 260 km s(-1). For H alpha a faint extension up to similar to- 450 km s(-1) can be seen probably arising from a small fraction of shocked high density clumps. We discuss these observations in the context of radiative shock models, which are qualitatively consistent with the observations. A fraction of the high ionization lines may originate in gas which has yet not had time to cool, explaining the difference in width between the low and high ionization lines. The maximum shock velocities seen in the optical lines are similar to 510 km s(-1). We expect the maximum width of especially the low ionization lines to increase with time.
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| 25. |
- Gröningsson, Per, et al.
(författare)
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High resolution spectroscopy of the line emission from the inner circumstellar ring of SN 1987A and its hot spots
- 2007
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- We discuss high resolution VLT/UVES observations (FWHM ~ 6 km/s) from October 2002 (day ~5700 past explosion) of the shock interaction of SN 1987A and its circumstellar ring. A nebular analysis of the narrow lines from the unshocked gas indicates gas densities of (1.5-5.0)E3 cm-3 and temperatures of 6.5E3-2.4E4 K. This is consistent with the thermal widths of the lines. From the shocked component we observe a large range of ionization stages from neutral lines to [Fe XIV]. From a nebular analysis we find that the density in the low ionization region is 4E6-1E7 cm-3. There is a clear difference in the high velocity extension of the low ionization lines and that of lines from [Fe X-XIV], with the latter extending up to ~ -390 km/s in the blue wing for [Fe XIV], while the low ionization lines extend to typically ~ -260 km/s. For H-alpha a faint extension up to ~ -450 km/s can be seen probably arising from a small fraction of shocked high density clumps. We discuss these observations in the context of radiative shock models, which are qualitatively consistent with the observations. A fraction of the high ionization lines may originate in gas which has yet not had time to cool down, explaining the difference in width between the low and high ionization lines. The maximum shock velocities seen in the optical lines are ~ 510 km/s. We expect the maximum width of especially the low ionization lines to increase with time.
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