| 1. |
- Johansson, Helena, 1981, et al.
(författare)
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A meta-analysis of the association of fracture risk and body mass index in women.
- 2014
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 1523-4681. ; 29:1, s. 223-33
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Tidskriftsartikel (refereegranskat)abstract
- Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20-105) years and follow up of 2.2 million person-years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30kg/m(2) ) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non-obese women. Compared to a BMI of 25kg/m(2) , the hazard ratio (HR) for osteoporotic fracture at a BMI of 35kg/m(2) was 0.87 (95% confidence interval [CI], 0.85-0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09-1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored. © 2014 American Society for Bone and Mineral Research.
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| 2. |
- Vandenput, Liesbeth, et al.
(författare)
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A meta-analysis of previous falls and subsequent fracture risk in cohort studies
- 2024
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 35:3, s. 469-494
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Tidskriftsartikel (refereegranskat)abstract
- SummaryThe relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm.IntroductionPrevious falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD).MethodsThe resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients.ResultsFalls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33–1.51) and men (HR 1.53, 95% CI 1.41–1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27–1.84) in men vs. HR 1.32 (95% CI 1.20–1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men.ConclusionsA previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.
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| 3. |
- Abdo, A. A., et al.
(författare)
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Multi-wavelength observations of the flaring gamma-ray blazar 3C 66A in 2008 October
- 2011
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 726:1, s. 43-
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Tidskriftsartikel (refereegranskat)abstract
- The BL Lacertae object 3C 66A was detected in a flaring state by the Fermi Large Area Telescope (LAT) and VERITAS in 2008 October. In addition to these gamma-ray observations, F-GAMMA, GASP-WEBT, PAIRITEL, MDM, ATOM, Swift, and Chandra provided radio to X-ray coverage. The available light curves show variability and, in particular, correlated flares are observed in the optical and Fermi-LAT gamma-ray band. The resulting spectral energy distribution can be well fitted using standard leptonic models with and without an external radiation field for inverse Compton scattering. It is found, however, that only the model with an external radiation field can accommodate the intra-night variability observed at optical wavelengths.
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| 4. |
- Abelev, B., et al.
(författare)
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Technical Design Report for the Upgrade of the ALICE Inner Tracking System
- 2014
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 41:8
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Tidskriftsartikel (refereegranskat)abstract
- LICE (A Large Ion Collider Experiment) is studying the physics of strongly interacting matter, and in particular the properties of the Quark–Gluon Plasma (QGP), using proton–proton, proton–nucleus and nucleus–nucleus collisions at the CERN LHC (Large Hadron Collider). The ALICE Collaboration is preparing a major upgrade of the experimental apparatus, planned for installation in the second long LHC shutdown in the years 2018–2019. A key element of the ALICE upgrade is the construction of a new, ultra-light, high-resolution Inner Tracking System (ITS) based on monolithic CMOS pixel detectors. The primary focus of the ITS upgrade is on improving the performance for detection of heavy-flavour hadrons, and of thermal photons and low-mass di-electrons emitted by the QGP. With respect to the current detector, the new Inner Tracking System will significantly enhance the determination of the distance of closest approach to the primary vertex, the tracking efficiency at low transverse momenta, and the read-out rate capabilities. This will be obtained by seven concentric detector layers based on a 50 μm thick CMOS pixel sensor with a pixel pitch of about 30×30 μm2. This document, submitted to the LHCC (LHC experiments Committee) in September 2013, presents the design goals, a summary of the R&D activities, with focus on the technical implementation of the main detector components, and the projected detector and physics performance.
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| 5. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 6. |
- Gravholt, Claus Højbjerg, et al.
(författare)
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Clinical and epidemiological description of aortic dissection in Turner's syndrome.
- 2006
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Ingår i: Cardiology in the young. - 1047-9511. ; 16:5, s. 430-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Women with Turner's syndrome have an increased risk of congenital cardiac malformations, ischaemic heart disease, hypertension and stroke. Aortic dissection seems to occur with increased frequency. AIM: To describe in more detail aortic dissection as encountered in Turner's syndrome, giving attention to clinical, histological and epidemiological aspects. MATERIALS AND METHODS: Based on a retrospective study, we describe the clinical, karyotypic, and epidemiological aspects of aortic dissection as encountered in cases of Turner's syndrome seen in Denmark and Sweden. RESULTS: The median age at onset of aortic dissection in 18 women was 35 years, ranging from 18 to 61 years. Fourteen of 18 women had a 45,X karyotype, while 2 patients had 45,X/45,XY, and 2 had the 45,X/46,X+r(X) complement, respectively. Echocardiography was performed in 10 of 18 patients before their acute illness, and showed signs of congenital cardiac disease, with either bifoliate aortic valves, dilation of the aortic root, or previous aortic coarctation evident in most patients. In 5 patients evidence of a bifoliate aortic valve was conclusive. Hypertension was present in 5 of 18 patients, while 10 of the patients died from aortic dissection, of so-called type A in 6, type B in 3, while in the final case the origin of dissection could not be determined. Biochemical analysis showed altered ratio between type I and type III collagen. Histology showed cystic medial necrosis in 3 of 7 cases. We estimated an incidence of dissection of 36 per 100,000 Turner's syndrome years, compared with an incidence of 6 per 100,000 in the general population, and a cumulated rate of incidence of 14, 73, 78, and 50 per 100,000 among 0-19, 20-29, 30-39, and 40+ year olds, respectively. CONCLUSION: Aortic dissection is extremely common in the setting of Turner's syndrome, and occurs early in life. Patients with Turner's syndrome should be offered a protocol for clinical follow-up similar to that provided for patients with Marfan syndrome, and each clinic should embrace a programme for follow-up.
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| 7. |
- Kahn, Fredrik, et al.
(författare)
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Previous SARS-CoV-2 infections and their impact on the protection from reinfection during the Omicron BA.5 wave – a nested case-control study among vaccinated adults in Sweden
- 2024
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Ingår i: IJID Regions. - 2772-7076. ; 10, s. 235-239
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We evaluated the protection afforded by SARS-CoV-2 infection-induced immunity against reinfection among working-age vaccinated individuals during a calendar period from June to December 2022 when Omicron BA.5 was the dominating subvariant in Scania County, Sweden. Methods: The study cohort (n = 71,592) mainly consisted of health care workers. We analyzed 4144 infected cases during the Omicron BA.5 dominance and 41,440 sex- and age-matched controls with conditional logistic regression. Results: The average protection against reinfection was marginal (16%, 95% confidence interval [CI] 7-23%) during the study period but substantially higher for recent infections. Recent infection (3-6 months) with Omicron BA.2 and BA.5 offered strong protection (86%, 95% CI 68-94% and 78%, 95% CI 69-84%), whereas more distant infection (6-12 months) with Omicron BA.1, BA.2, and the variants before Omicron offered marginal or no protection. Conclusions: These findings suggest that infection-induced immunity contributes to short-term population protection against infection with the subvariant BA.5 among working-age vaccinated individuals but wanes considerably with time, independent of the virus variant.
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| 8. |
- Mortazavi, Susanne E., et al.
(författare)
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A retrospective cohort study of the effect of SARS-CoV-2 point of care rapid RT-PCR at the Emergency Department on targeted admission
- 2022
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 22, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Background: To prevent nosocomial transmission of SARS-CoV-2, infection prevention control (IPC) measures are implemented for patients with symptoms compatible with COVID-19 until reliable test results are available. This delays admission to the most appropriate ward based on the medical condition. SARS-CoV-2 rapid antigen detection (RAD) tests and point-of-care (POC) rapid RT-PCR (VitaPCR) were introduced at emergency department (ED) at Skåne University Hospital, Sweden in late 2020, but the consequence on patient flow and targeted admission is unknown. Methods: Patients presenting at the emergency department of a referral hospital (N = 2940) between 13-Nov-2020 and 12-Jan-2021 were included. The study period was delimited into three periods by the introduction of RAD tests and the VitaPCR. Participant data was collected from hospital records, and outcome variables were Length-of-Stay (LoS), intrahospital transfers and targeted admission to COVID-19 ward. Results: Compared to baseline (RT-PCR only), RAD tests reduced ED Length-of-Stay (LoS) for participants with positive tests. Negative VitaPCR results reduced mean hospital LoS by 1.5 (95% CI 0.3–2.7) days and admissions to COVID-19 wards from 34.5 (95% CI 28.9–40.5) to 14.7 (95% CI 11.1–19.1) per 100 admissions and reduced transfers between hospital wards in the first 5 days from 50.0 (95% CI 45.0–55.0) to 34.0 (95% CI 30.3–37.9) per 100 admissions. Conclusion: RAD tests enabled prompt detection of SARS-CoV-2 infection which had pronounced effects on LoS at the ED. Negative VitaPCR enabled cessation of IPC measures and a negative test was associated with increased targeted admissions, reduced intrahospital transfers and shorter LoS at the hospital.
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| 9. |
- Sarneel, Judith M., et al.
(författare)
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Reading tea leaves worldwide : decoupled drivers of initial litter decomposition mass-loss rate and stabilization
- 2024
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Ingår i: Ecology Letters. - : John Wiley & Sons. - 1461-023X .- 1461-0248. ; 27:5
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Tidskriftsartikel (refereegranskat)abstract
- The breakdown of plant material fuels soil functioning and biodiversity. Currently, process understanding of global decomposition patterns and the drivers of such patterns are hampered by the lack of coherent large-scale datasets. We buried 36,000 individual litterbags (tea bags) worldwide and found an overall negative correlation between initial mass-loss rates and stabilization factors of plant-derived carbon, using the Tea Bag Index (TBI). The stabilization factor quantifies the degree to which easy-to-degrade components accumulate during early-stage decomposition (e.g. by environmental limitations). However, agriculture and an interaction between moisture and temperature led to a decoupling between initial mass-loss rates and stabilization, notably in colder locations. Using TBI improved mass-loss estimates of natural litter compared to models that ignored stabilization. Ignoring the transformation of dead plant material to more recalcitrant substances during early-stage decomposition, and the environmental control of this transformation, could overestimate carbon losses during early decomposition in carbon cycle models.
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| 10. |
- Styrkarsdottir, Unnur, et al.
(författare)
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GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 – 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10 −42 , β = −0.090) and confers risk of hip fracture (P = 1.0 × 10 −8 , OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.
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| 11. |
- Styrkarsdottir, Unnur, et al.
(författare)
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Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:5, s. 801-805
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Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study of total hip replacements, based on variants identified through whole-genome sequencing, which included 4,657 Icelandic patients and 207,514 population controls. We discovered two rare signals that strongly associate with osteoarthritis total hip replacement: a missense variant, c.1141G>C (p.Asp369His), in the COMP gene (allelic frequency = 0.026%, P = 4.0 × 10-12, odds ratio (OR) = 16.7) and a frameshift mutation, rs532464664 (p.Val330Glyfs∗106), in the CHADL gene that associates through a recessive mode of inheritance (homozygote frequency = 0.15%, P = 4.5 × 10-18, OR = 7.71). On average, c.1141G>C heterozygotes and individuals homozygous for rs532464664 had their hip replacement operation 13.5 years and 4.9 years earlier than others (P = 0.0020 and P = 0.0026), respectively. We show that the full-length CHADL transcript is expressed in cartilage. Furthermore, the premature stop codon introduced by the CHADL frameshift mutation results in nonsense-mediated decay of the mutant transcripts.
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| 12. |
- Svensson, Joel, et al.
(författare)
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A Serosurvey of Tick-Borne Encephalitis Virus in Sweden: Different Populations and Geographical Locations
- 2021
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Ingår i: Vector-Borne and Zoonotic Diseases. - : Mary Ann Liebert Inc. - 1557-7759 .- 1530-3667. ; 21:8, s. 614-619
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Tidskriftsartikel (refereegranskat)abstract
- AbstractBackground: New risk areas for tick-borne encephalitis (TBE) are emerging and the spread of disease and vaccine coverage is unclear in Sweden. We wanted to study the prevalence and levels of TBE-virus (TBEV) antibodies in southern Sweden, and to investigate whether there were individuals with undiagnosed TBE.Materials and Methods: Two cohorts of sera were collected: One group of anonymous individuals in rural areas (AIRA) in Skåne and one group of volunteers who often got tick-bites (tick-bitten individuals [TBI]). An enzyme-linked immunosorbent assay for TBEV IgM and IgG was performed, as well as a TBEV neutralization test (NT) in selected individuals.Results: In the AIRA group, there was an IgG seropositivity of 5.3%. There were individuals with high antibody levels both in areas previously considered as risk areas (Bromölla and Knislinge), as well as in another area (Tyringe). In the TBI group, 45% of the individuals were vaccinated according to the questionnaires and IgG seropositivity was 28%. A lower seroprevalence and levels of antibodies were seen in the middle-aged group (50–69 years) compared with younger or elderly study participants. A positive NT revealed several individuals with suspected undiagnosed episodes of TBE.Conclusion: Subclinical or misdiagnosed cases have probably occurred in Skåne. Middle-aged individuals had lower levels of IgG, which could indicate either less tick exposure or a lower vaccine response. Less than half of the TBI were vaccinated, an indication that more information about the disease and vaccine might be needed. We conclude that the study motivates an increased awareness of TBEV in the region.
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| 13. |
- Zheng, Hou-Feng, et al.
(författare)
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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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