| 1. |
- Kanis, J A, et al.
(författare)
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Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.
- 2023
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Nature. - 1433-2965 .- 0937-941X. ; 34:12, s. 2027-2045
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Tidskriftsartikel (refereegranskat)abstract
- A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX.The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD).We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted β-coefficients.A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination.A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.
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| 2. |
- Vandenput, L., 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 Nature. - 0937-941X .- 1433-2965. ; 35:3, s. 469-494
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Tidskriftsartikel (refereegranskat)abstract
- Summary: The 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. Introduction: Previous 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). Methods: The 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. Results: Falls 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. Conclusions: A 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. |
- Vandenput, Liesbeth, 1974, et al.
(författare)
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Update of the fracture risk prediction tool FRAX : a systematic review of potential cohorts and analysis plan
- 2022
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 33:10, s. 2103-2136
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Forskningsöversikt (refereegranskat)abstract
- Summary: We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures.Introduction: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors.Methods: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible.Results: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed.Conclusions: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).
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| 4. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 5. |
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| 6. |
- Enzell, Jonas
(författare)
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Toward Realistic Failure Evaluations for Concrete Buttress Dams
- 2023
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Concrete dams, complex structures supporting massive loads, have traditionally been assessed using simplified 2D analytical stability analyses based on the rigid body assumption. Previous studies have shown that 3D behavior, such as the interaction between the monoliths and the valley's geology, can greatly impact the load-bearing capacity of gravity dams but remains largely unexplored in buttress dams. Internal failure modes have also been shown to impact the load-bearing capacity and failure modes of concrete dams. The dam breach geometry and breach development time are important factors for flooding simulations used for emergency plans. There are no available methods for estimating the breach parameters for concrete dams. Instead, they are usually assumed based on simplified national recommendations, which introduces large uncertainties in the analysis. Thus, developing methods to estimate failure behavior in concrete gravity and buttress dams could significantly enhance flood simulation accuracy.This licentiate thesis aims to develop more realistic analysis methods for determining the load-bearing capacity and failure behavior of concrete buttress dams. To achieve this aim, studies using physical model tests were conducted to determine the 3D effects of the boundary conditions and the interaction between the monoliths and verify the results from finite element simulations. Numerical studies were performed to examine the failure behavior of concrete buttress dams and to determine suitable methods for such simulations. The results from the physical model tests suggest that 3D effects significantly impact the load-bearing capacity and the failure behavior of concrete buttress dams. Therefore, the entire dam should be considered in stability analyses rather than just single monoliths. The numerical studies showed that finite element models could successfully simulate dam failures, including the 3D behavior of concrete buttress dams and internal failure modes. However, there remain questions about the best methods for representing phenomena such as first-order roughness, valley shape, and fracture planes in these models.The model tests showed that while dam failures can occur abruptly with little to no initial signs of displacement, the presence of rough foundations, cohesion, and rock-strengthening measures in real-world dams suggests actual dam failures may not be as sudden. The results helped establish knowledge in the field to potentially create better alarm limits for automatic monitoring systems.
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| 7. |
- Lindgren, Cecilia M, et al.
(författare)
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Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.
- 2009
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:6, s. e1000508-
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
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| 8. |
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| 9. |
- Pateras, Ioannis S., et al.
(författare)
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Short term starvation potentiates the efficacy of chemotherapy in triple negative breast cancer via metabolic reprogramming
- 2023
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Ingår i: Journal of Translational Medicine. - : BioMed Central (BMC). - 1479-5876. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chemotherapy (CT) is central to the treatment of triple negative breast cancer (TNBC), but drug toxicity and resistance place strong restrictions on treatment regimes. Fasting sensitizes cancer cells to a range of chemotherapeutic agents and also ameliorates CT-associated adverse effects. However, the molecular mechanism(s) by which fasting, or short-term starvation (STS), improves the efficacy of CT is poorly characterized.Methods: The differential responses of breast cancer or near normal cell lines to combined STS and CT were assessed by cellular viability and integrity assays (Hoechst and PI staining, MTT or H2DCFDA staining, immunofluorescence), metabolic profiling (Seahorse analysis, metabolomics), gene expression (quantitative real-time PCR) and iRNA-mediated silencing. The clinical significance of the in vitro data was evaluated by bioinformatical integration of transcriptomic data from patient data bases: The Cancer Genome Atlas (TCGA), European Genome-phenome Archive (EGA), Gene Expression Omnibus (GEO) and a TNBC cohort. We further examined the translatability of our findings in vivo by establishing a murine syngeneic orthotopic mammary tumor-bearing model.Results: We provide mechanistic insights into how preconditioning with STS enhances the susceptibility of breast cancer cells to CT. We showed that combined STS and CT enhanced cell death and increased reactive oxygen species (ROS) levels, in association with higher levels of DNA damage and decreased mRNA levels for the NRF2 targets genes NQO1 and TXNRD1 in TNBC cells compared to near normal cells. ROS enhancement was associated with compromised mitochondrial respiration and changes in the metabolic profile, which have a significant clinical prognostic and predictive value. Furthermore, we validate the safety and efficacy of combined periodic hypocaloric diet and CT in a TNBC mouse model.Conclusions: Our in vitro, in vivo and clinical findings provide a robust rationale for clinical trials on the therapeutic benefit of short-term caloric restriction as an adjuvant to CT in triple breast cancer treatment.
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| 10. |
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| 11. |
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| 12. |
- Glinatsi, D., et al.
(författare)
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Head-to-head comparison of aggressive conventional therapy and three biological treatments and comparison of two de-escalation strategies in patients who respond to treatment: Study protocol for a multicenter, randomized, open-label, blinded-assessor, phase 4 study
- 2017
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: New targeted therapies and improved treatment strategies have dramatically improved the outcomes of patients with rheumatoid arthritis (RA). However, it is unknown whether different early aggressive interventions can induce stable remission or a low-active disease state that can be maintained with conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy, and whether they differ in efficacy and safety. The Nordic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) study will assess and compare (1) the proportion of patients who achieve remission in a head-to-head comparison between csDMARD plus glucocorticoid therapy and three different biological DMARD (bDMARD) therapies with different modes of action and (2) two de-escalation strategies in patients who respond to first-line therapy. Methods/design: In a pragmatic, 80-160-week, multicenter, randomized, open-label, assessor-blinded, phase 4 study, 800 patients with early RA (symptom duration less than 24 months) are randomized 1:1:1:1 to one of four different treatment arms: (1) aggressive csDMARD therapy with methotrexate + sulphasalazine + hydroxychloroquine + i.a. glucocorticoids (arm 1A) or methotrexate + prednisolone p.o. (arm 1B), (2) methotrexate + certolizumab-pegol, (3) methotrexate + abatacept, or (4) methotrexate + tocilizumab. The primary clinical endpoint is the proportion of patients reaching Clinical Disease Activity Index (CDAI) remission at week 24. Patients in stable remission over 24 consecutive weeks enter part 2 of the study earliest after 48 weeks. Patients not achieving sustained CDAI remission over 24 consecutive weeks, exit the study after 80 weeks. In part 2, patients are re-randomized to two different de-escalation strategies, either immediate or delayed (after 24 weeks) tapering, followed by cessation of study medication. All patients remain on stable doses of methotrexate. The primary clinical endpoint in part 2 is the proportion of patients in remission (CDAI ≤2.8) 24 weeks after initiating treatment de-escalation. Radiographic assessment will be performed regularly throughout the trial, and blood and urine samples will be stored in a biobank for later biomarker analyses. Discussion: NORD-STAR is the first investigator-initiated, randomized, early RA trial to compare (1) csDMARD and three different bDMARD therapies head to head and (2) two different de-escalation strategies. The trial has the potential to identify which treatment strategy to apply in early RA to achieve the best possible outcomes for both patients and society. Trial registration:NCT01491815and NCT02466581. Registered on 8 December 2011 and May 2015, respectively. EudraCT: 2011-004720-35 © 2017 The Author(s).
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| 13. |
- Kepp, Kasper P., et al.
(författare)
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Panel stacking is a threat to consensus statement validity
- 2024
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier. - 0895-4356 .- 1878-5921. ; 173
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Tidskriftsartikel (refereegranskat)abstract
- Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members toward one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but nonfinancial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analyzing in depth a recent high-impact Delphi consensus statement on COVID-19 recommendations as a case example. We demonstrate that many of the selected panel members and at least 35% of the core panel members had advocated toward COVID-19 elimination (Zero-COVID) during the pandemic and were leading members of aggressive advocacy groups. These advocacy conflicts were not declared in the Delphi consensus publication, with rare exceptions. Therefore, we propose that consensus statements should always require rigorous evidence synthesis and maximal transparency on potential biases toward advocacy or lobbyist groups to be valid. While advocacy can have many important functions, its biased impact on consensus panels should be carefully avoided.
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| 14. |
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| 15. |
- Paluch, Amanda E., et al.
(författare)
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Daily steps and all-cause mortality : a meta-analysis of 15 international cohorts
- 2022
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Ingår i: The Lancet Public Health. - : Elsevier. - 2468-2667. ; 7:3, s. e219-e228
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although 10 000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality.METHODS: In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged ≥18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose-response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inverse-variance weighted random effects models.FINDINGS: We identified 15 studies, of which seven were published and eight were unpublished, with study start dates between 1999 and 2018. The total sample included 47 471 adults, among whom there were 3013 deaths (10·1 per 1000 participant-years) over a median follow-up of 7·1 years ([IQR 4·3-9·9]; total sum of follow-up across studies was 297 837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3, and 10 901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 0·60 (95% CI 0·51-0·71) for quartile 2, 0·55 (0·49-0·62) for quartile 3, and 0·47 (0·39-0·57) for quartile 4. Restricted cubic splines showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of steps per day until 6000-8000 steps per day and among adults younger than 60 years until 8000-10 000 steps per day. Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping rates and mortality was attenuated but remained significant for a peak of 30 min (HR 0·67 [95% CI 0·56-0·83]) and a peak of 60 min (0·67 [0·50-0·90]), but not significant for time (min per day) spent walking at 40 steps per min or faster (1·12 [0·96-1·32]) and 100 steps per min or faster (0·86 [0·58-1·28]).INTERPRETATION: Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health promotion of physical activity.FUNDING: US Centers for Disease Control and Prevention.
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| 16. |
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| 17. |
- Scott, D., et al.
(författare)
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Mid-calf skeletal muscle density and its associations with accelerometer-determined physical activity, bone health and incident 12-month falls in older adults : the healthy ageing initiative
- 2019
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 30, s. S59-S59
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: To determine associations of mid-calf muscle density, an indicator of intramuscular fat infiltration, with objectively-determined physical activity, bone health and 12-month falls risk in community-dwelling older adults.Methods: 2167 community-dwelling Swedish men and women who participated in the Healthy Ageing Initiative study at age 70 were included in this analysis. Mid-calf muscle density (mg/cm3; higher values indicate lower intramuscular fat content) at the proximal tibia, and bone parameters at the distal and proximal tibia and radius, were assessed by peripheral quantitative computed tomography. Whole-body lean and fat mass, lumbar spine and total hip BMD were assessed by DXA. Participants completed the timed up-and-go (TUG) test, 7-day accelerometer measurements of physical activity intensity, and self-reported falls data were collected 6 and 12 months later.Results: Only moderate/vigorous intensity physical activity, not sedentary or light activity, was positively associated with mid-calf muscle density (B=0.002 mg/cm3 per minute; P<0.001). 258 (12%) participants experienced a fall within 12 months. After adjustment for confounders including sex, fasting glucose, average daily moderate/vigorous intensity physical activity, and total lean mass at baseline, each mg/cm3 increase in mid-calf muscle density was associated with 4% and 11% reduced likelihood of experiencing a fall or multiple falls, respectively (both P<0.05). The association with multiple falls remained significant after further adjustment for TUG time (OR: 0.91 95%CI: 0.83, 0.99). In multivariable models, mid-calf muscle density was not associated with total hip BMD, was negatively associated with lumbar spine BMD (B=-0.003, 95%CI -0.005, -0.003 g/cm2), and at the radius, was positively associated only with proximal cortical density (B=0.784, 95%CI 0.246, 1.323 mg/cm3). However, at the tibia, muscle density was positively associated with distal total and trabecular BMD, and also proximal total and cortical BMD, cortical thickness and stress-strain index (all P<0.05).Conclusions: Higher mid-calf muscle density is independently associated with decreased likelihood for multiple incident falls and appears to have localised positive effects on bone structure. Improvements in lower-limb muscle density may be achievable through increasing participation in moderate/vigorous intensity activity and could potentially reduce fracture risk in older adults.
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| 18. |
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| 19. |
- Vandenput, Liesbeth, et al.
(författare)
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A meta-analysis of previous falls and subsequent fracture risk in cohort studies
- 2024
-
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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| 20. |
- Barnett, Paul D, et al.
(författare)
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Motion adaptation and the velocity coding of natural scenes
- 2010
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 20:11, s. 994-999
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Tidskriftsartikel (refereegranskat)abstract
- Estimating relative velocity in the natural environment is challenging because natural scenes vary greatly in contrast and spatial structure. Widely accepted correlation-based models for elementary motion detectors (EMDs) are sensitive to contrast and spatial structure and consequently generate ambiguous estimates of velocity [1]. Identified neurons in the third optic lobe of the hoverfly can reliably encode the velocity of natural images largely independent of contrast [2], despite receiving inputs directly from arrays of such EMDs [3, 4]. This contrast invariance suggests an important role for additional neural processes in robust encoding of image motion [2, 5, 6]. However, it remains unclear which neural processes are contributing to contrast invariance. By recording from horizontal system neurons in the hoverfly lobula, we show two activity-dependent adaptation mechanisms acting as near-ideal normalizers for images of different contrasts that would otherwise produce highly variable response magnitudes. Responses to images that are initially weak neural drivers are boosted over several hundred milliseconds. Responses to images that are initially strong neural drivers are reduced over longer time scales. These adaptation mechanisms appear to be matched to higher-order natural image statistics reconciling the neurons' accurate encoding of image velocity with the inherent ambiguity of correlation-based motion detectors.
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| 21. |
- Berglund, Lisa, et al.
(författare)
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Novel blocker of NFAT activation inhibits IL-6 production in human myometrial arteries and reduces vascular smooth muscle cell proliferation
- 2007
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Ingår i: American Journal of Physiology: Cell Physiology. - : American Physiological Society. - 1522-1563 .- 0363-6143. ; 292:3, s. 1167-1178
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Tidskriftsartikel (refereegranskat)abstract
- The calcineurin/nuclear factor of activated T cells ( NFAT) signaling pathway has been found to play a role in regulating growth and differentiation in several cell types. However, the functional significance of NFAT in the vasculature is largely unclear. Here we show that NFATc1, NFATc3, and NFATc4 are expressed in human myometrial arteries. Confocal immunofluorescence and Western blot analysis revealed that endothelin-1 efficiently increases NFATc3 nuclear accumulation in native arteries. Endothelin-1 also stimulates NFAT-dependent transcriptional activity, as shown by a luciferase reporter assay. Both the agonist-induced NFAT nuclear accumulation and transcriptional activity were prevented by the calcineurin inhibitor CsA and by the novel NFAT blocker A-285222. Chronic inhibition of NFAT significantly reduced IL-6 production in intact myometrial arteries and inhibited cell proliferation in vascular smooth muscle cells cultured from explants from the same arteries. Furthermore, by using small interfering RNA-mediated reduction of NFATc3, we show that this isoform is involved in the regulation of cell proliferation. Protein synthesis in intact arteries was investigated using autoradiography of [S-35] methionine incorporation in serum-free culture. Inhibition of NFAT signaling did not affect overall protein synthesis or specifically the synthesis rates of major proteins associated with the contractile/cytoskeletal system. An intact contractile phenotype under these conditions was also shown by unchanged force response to depolarization or agonist stimulation. Our results demonstrate NFAT expression and activation in native human vessels and point out A-285222 as a powerful pharmacological blocker of NFAT signaling in the vasculature.
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| 23. |
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| 24. |
- Bohlin, Alexis, et al.
(författare)
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Direct measurement of S-branch N(2)-H(2) Raman linewidths using time-resolved pure rotational coherent anti-Stokes Raman spectroscopy.
- 2012
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 137:7
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Tidskriftsartikel (refereegranskat)abstract
- S-branch N(2)-H(2) Raman linewidths have been measured in the temperature region 294-1466 K using time-resolved dual-broadband picosecond pure rotational coherent anti-Stokes Raman spectroscopy (RCARS). Data are extracted by mapping the dephasing rates of the CARS signal temporal decay. The J-dependent coherence decays are detected in the time domain by following the individual spectral lines as a function of probe delay. The linewidth data set was employed in spectral fits of N(2) RCARS spectra recorded in binary mixtures of N(2) and H(2) at calibrated temperature conditions up to 661 K using a standard nanosecond RCARS setup. In this region, the set shows a deviation of less than 2% in comparison with thermocouples. The results provide useful knowledge for the applicability of N(2) CARS thermometry on the fuel-side of H(2) diffusion flames.
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| 25. |
- Brose, Ulrich, et al.
(författare)
-
Predicting the consequences of species lossusing size-structured biodiversity approaches
- 2017
-
Ingår i: Biological Reviews. - : Wiley-Blackwell. - 1464-7931 .- 1469-185X. ; 92:2, s. 684-697
-
Forskningsöversikt (refereegranskat)abstract
- Understanding the consequences of species loss in complex ecological communities is one of the great challenges in current biodiversity research. For a long time, this topic has been addressed by traditional biodiversity experiments. Most of these approaches treat species as trait-free, taxonomic units characterizing communities only by species number without accounting for species traits. However, extinctions do not occur at random as there is a clear correlation between extinction risk and species traits. In this review, we assume that large species will be most threatened by extinction and use novel allometric and size-spectrum concepts that include body mass as a primary species trait at the levels of populations and individuals, respectively, to re-assess three classic debates on the relationships between biodiversity and (i) food-web structural complexity, (ii) community dynamic stability, and (iii) ecosystem functioning. Contrasting current expectations, size-structured approaches suggest that the loss of large species, that typically exploit most resource species, may lead to future food webs that are less interwoven and more structured by chains of interactions and compartments. The disruption of natural body-mass distributions maintaining food-web stability may trigger avalanches of secondary extinctions and strong trophic cascades with expected knock-on effects on the functionality of the ecosystems. Therefore, we argue that it is crucial to take into account body size as a species trait when analysing the consequences of biodiversity loss for natural ecosystems. Applying size-structured approaches provides an integrative ecological concept that enables a better understanding of each species' unique role across communities and the causes and consequences of biodiversity loss.
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| 26. |
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| 27. |
- Buentke, E, et al.
(författare)
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Glucocorticoid-induced cell death is mediated through reduced glucose metabolism in lymphoid leukemia cells
- 2011
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Ingår i: Blood Cancer Journal. - : Macmillan Publishers Limited. - 2044-5385. ; 1:e31, s. 9-
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Tidskriftsartikel (refereegranskat)abstract
- Malignant cells are known to have increased glucose uptake and accelerated glucose metabolism. Using liquid chromatography and mass spectrometry, we found that treatment of acute lymphoblastic leukemia (ALL) cells with the glucocorticoid (GC) dexamethasone (Dex) resulted in profound inhibition of glycolysis. We thus demonstrate that Dex reduced glucose consumption, glucose utilization and glucose uptake by leukemic cells. Furthermore, Dex treatment decreased the levels of the plasma membrane-associated glucose transporter GLUT1, thus revealing the mechanism for the inhibition of glucose uptake. Inhibition of glucose uptake correlated with induction of cell death in ALL cell lines and in leukemic blasts from ALL patients cultured ex vivo. Addition of di-methyl succinate could partially overcome cell death induced by Dex in RS4;11 cells, thereby further supporting the notion that inhibition of glycolysis contributes to the induction of apoptosis. Finally, Dex killed RS4;11 cells significantly more efficiently when cultured in lower glucose concentrations suggesting that modulation of glucose levels might influence the effectiveness of GC treatment in ALL. In summary, our data show that GC treatment blocks glucose uptake by leukemic cells leading to inhibition of glycolysis and that these effects play an important role in the induction of cell death by these drugs.
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| 28. |
- Bultmark, F., et al.
(författare)
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Tests of the efficiency of an augmented distorted planewave basis in electronic structure calculations
- 2008
-
Ingår i: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 20:23, s. 235241-
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Tidskriftsartikel (refereegranskat)abstract
- An augmented distorted planewave plus local orbital basis set has been developed and implemented in a simple fashion in order to test its efficiency for electronic structure calculations. It is based on the idea of using distorted planewaves (Gygi 1993 Phys. Rev. B 48 11692) as basis functions in the interstitial region instead of ordinary planewaves, as in the usual linearized augmented planewave and augmented planewave plus local orbitals methods. This is shown to lead to a significantly more rapid convergence for open structures as well as a modestly improved convergence for close packed structures.
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| 29. |
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| 30. |
- Chaurasia, Chandra S., et al.
(författare)
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AAPS-FDA workshop white paper : microdialysis principles, application and regulatory perspectives
- 2007
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 24:5, s. 1014-1025
-
Tidskriftsartikel (refereegranskat)abstract
- Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (microD) is the only tool available that explicitly provides data on the extracellular space. Although microD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of microD in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of microD in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on microD as a tool in drug research and development.
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| 31. |
- Chaurasia, Chandra S., et al.
(författare)
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AAPS-FDA Workshop White Paper : microdialysis principles, application, and regulatory perspectives
- 2007
-
Ingår i: Journal of clinical pharmacology. - : Wiley. - 0091-2700 .- 1552-4604. ; 47:5, s. 589-603
-
Tidskriftsartikel (refereegranskat)abstract
- Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (μD) is the only tool available that explicitly provides data on the extracellular space. Although μD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of μD in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of μD in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on μD as a tool in drug research and development.
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| 32. |
- Dahlman, Ingrid, et al.
(författare)
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A unique role of monocyte chemoattractant protein 1 among chemokines in adipose tissue of obese subjects
- 2005
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 90:10, s. 5834-5840
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Low-grade inflammation in adipose tissue may contribute to insulin resistance in obesity. However, the roles of individual inflammatory mediators in adipose tissue are poorly understood. Objectives: The objective of this study was to determine which inflammation markers are most overexpressed at the gene level in adipose tissue in human obesity and how this relates to corresponding protein secretion. Design: We examined gene expression profiles in 17 lean and 20 obese subjects. The secretory pattern of relevant corresponding proteins was examined in human sc adipose tissue or isolated fat cells in vitro and in vivo in several obese or lean cohorts. Results: In ranking gene expression, defined pathways associated with obesity and immune and defense responses scored high. Among seven markedly overexpressed chemokines, only monocyte chemoattractant protein 1 (MCP1) was released from adipose tissue and isolated fat cells in vitro. In obesity, the secretion and expression of MCP1 in adipose tissue pieces were more than 6- and 2-fold increased, respectively, but there was no change in circulating MCP1 levels. There was no net release of MCP1, but there was a net release of leptin, in vivo from adipose tissue into the circulation. Conclusions: Obesity is associated with the increased expression of several chemokine genes in adipose tissue. However, only MCP1 is secreted into the extracellular space, where it primarily acts as a local factor, because little or no spillover into the circulation occurs. MCP1 influences the function of adipocytes, is a recruitment factor for macrophages, and may be a crucial link among chemokines between adipose tissue inflammation and insulin resistance.
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| 33. |
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| 34. |
- Dyakova, Olga, et al.
(författare)
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A higher order visual neuron tuned to the spatial amplitude spectra of natural scenes
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Animal sensory systems are optimally adapted to those features typically encountered in natural surrounds, thus allowing neurons with limited bandwidth to encode challengingly large input ranges. Natural scenes are not random, and peripheral visual systems in vertebrates and insects have evolved to respond efficiently to their typical spatial statistics. The mammalian visual cortex is also tuned to natural spatial statistics, but less is known about coding in higher order neurons in insects. To redress this we here record intracellularly from a higher order visual neuron in the hoverfly. We show that the cSIFE neuron, which is inhibited by stationary images, is maximally inhibited when the slope constant of the amplitude spectrum is close to the mean in natural scenes. The behavioural optomotor response is also strongest to images with naturalistic image statistics. Our results thus reveal a close coupling between the inherent statistics of natural scenes and higher order visual processing in insects.
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| 35. |
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| 36. |
- Elinder, Malin, et al.
(författare)
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Experimental Validation of a Fragment Library for Lead Discovery Using SPR Biosensor Technology
- 2011
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Ingår i: Journal of Biomolecular Screening. - : Elsevier BV. - 1087-0571 .- 1552-454X. ; 16:1, s. 15-25
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Tidskriftsartikel (refereegranskat)abstract
- A new fragment library for lead discovery has been designed and experimentally validated for use in surface plasmon resonance (SPR) biosensor-based screening. The 930 compounds in the library were selected from 4.6 million commercially available compounds using a series of physicochemical and medicinal chemistry filters. They were screened against 3 prototypical drug targets: HIV-1 protease, thrombin and carbonic anhydrase, and a nontarget: human serum albumin. compound solubility was not a problem under the conditions used for screening. The high sensitivity of the sensor surfaces allowed the detection of interactions for 35% to 97% of the fragments, depending on the target protein. None of the fragments was promiscuous (i.e., interacted with a stoichiometry ≥5:1 with all 4 proteins), and only 2 compounds dissociated slowly from all 4 proteins. The use of several targets proved valuable since several compounds would have been disqualified from the library on the grounds of promiscuity if fewer target proteins had been used. The experimental procedure allowed an efficient evaluation and exploration of the new fragment library and confirmed that the new library is suitable for SPR biosensor-based screening.
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| 37. |
- Enzell, Jonas, et al.
(författare)
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Modellförsök stärker betongdammars säkerhet
- 2023
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Ingår i: Bygg och Teknik. - 0281-658X .- 2002-8350. ; 115:6
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Dammhaverier är mycket ovanliga och därför är kunskapen om brottförloppet vid ett potentiellt dammbrott begränsad. Uppstår brottet utan förvarning, eller finns tidiga tecken på allvarliga problem? Hur utvecklas brottsbräschen under brottförloppet? Detta är frågor som blivit än mer aktuella efter tre internationella dammhaverier under 2023. För att söka svar har en serie skalmodellförsök utförts där haverier av betongdammar simuleras. En viktig parameter vid säkerhetsbedömningen av en betongdamm består i att utvärdera dess stabilitet. Förenklat görs dettag enom att jämföra om dammkroppens vikt är tillräcklig för att stå emot lasten från vattnets tryck. Traditionellt beaktas enbart en mindre del av en betongdamm när dess stabilitet utvärderas men de nya försöken indikerar att det vore eftersträvansvärt att undersöka hela dammen samtidigt eftersom lasten fördelas mellan konstruktionsdelarna. Många betongdammars tillstånd övervakas idag genom automatiska mätningarav till exempel vattenstånd, förskjutningar och grundvattentryck. Dock finns det ingen standardiserad metod för att definiera larmgränser,vilket detta projekt syftar till att utveckla i framtiden.
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| 38. |
- Enzell, Jonas, et al.
(författare)
-
Physical Model Tests of Concrete Buttress Dams with Failure Imposed by Hydrostatic Water Pressure
- 2023
-
Ingår i: Water. - : MDPI. - 2073-4441. ; 15:20
-
Tidskriftsartikel (refereegranskat)abstract
- Although the failure of a concrete dam is a complex and highly dynamic process, the current safety assessments of concrete gravity and buttress dams rely on a simplified 2D stability analysis, which neglects the load redistribution due to 3D monolith interactions and the valley shape. In addition, the estimation of breach parameters in concrete dams is based on assumptions rather than analyses, and better prediction methods are needed. Model tests have been conducted to increase the understanding of the failure behavior of concrete dams. A scale model buttress dam, with a scale of 1:15, consisting of 5 monoliths that were 1.2 m in height and 4 m in width, was constructed and loaded to failure using water pressure. The model dam had detachable abutment supports and shear keys to permit variations in the 3D behavior. The results showed that the shear transfer was large between the monoliths and that the failure of a single dam monolith is unlikely. A greater lateral restraint gives not only a higher failure load but also a better indication of impending failure. These findings suggest that the entire dam, including its boundary conditions, should be considered during a stability assessment. The results also suggest that the common assumption in dam safety codes that a single monolith fails during flooding analysis is not conservative. The dataset obtained provides a foundation for the future development of dam-monitoring alarm limits and for predictive models of dam-breaching processes.
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| 39. |
- Enzell, Jonas, et al.
(författare)
-
Realistic numerical simulations of concrete dam failures
- 2023
-
Konferensbidrag (refereegranskat)abstract
- Dam failures may have catastrophic consequences, including the release of largeamounts of water, significant property damage, and loss of life. However, safety assessments ofconcrete gravity and buttress dams often rely on simplified methods that do not consider the interactionbetween monoliths, the shape of the foundation or the presence of stiff abutments. Numericalmodeling can be a valuable tool for analyzing the stability of these dams, but it can bedifficult to validate these models due to a lack of documented dam failures. This paper presentsthe results of a numerical study examining the ability of dynamic finite element analyses to simulatedam failures. The study used the results from a series of physical model tests as a case studyfor validation. It was found that the numerical model was able to accurately reproduce the failuremode and breach development observed in the physical model tests and capture the effect of theloading rate on the failure mode and time for the failure to develop. Simulations were also performedin prototype scale to verify that the model tests were representative of a real dam failure.Further research is needed to determine the reliability of the numerical models under differentloading conditions and in realistic geological settings. However, these findings suggest that numericalmodeling can be a valuable tool for analyzing the stability of concrete gravity and buttressdams and predicting the development of failures.
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| 40. |
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| 41. |
- Hallström, Teresia, et al.
(författare)
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Immune Evasion of Moraxella catarrhalis Involves Ubiquitous Surface Protein A-Dependent C3d Binding.
- 2011
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Ingår i: Journal of immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 186, s. 3120-3129
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Tidskriftsartikel (refereegranskat)abstract
- The complement system plays an important role in eliminating invading pathogens. Activation of complement results in C3b deposition (opsonization), phagocytosis, anaphylatoxin (C3a, C5a) release, and consequently cell lysis. Moraxella catarrhalis is a human respiratory pathogen commonly found in children with otitis media and in adults with chronic obstructive pulmonary disease. The species has evolved multiple complement evasion strategies, which among others involves the ubiquitous surface protein (Usp) family consisting of UspA1, A2, and A2 hybrid. In the present study, we found that the ability of M. catarrhalis to bind C3 correlated with UspA expression and that C3 binding contributed to serum resistance in a large number of clinical isolates. Recombinantly expressed UspA1 and A2 inhibit both the alternative and classical pathways, C3b deposition, and C3a generation when bound to the C3 molecule. We also revealed that the M. catarrhalis UspA-binding domain on C3b was located to C3d and that the major bacterial C3d-binding domains were within UspA1(299-452) and UspA2(165-318). The interaction with C3 was not species specific since UspA-expressing M. catarrhalis also bound mouse C3 that resulted in inhibition of the alternative pathway of mouse complement. Taken together, the binding of C3 to UspAs is an efficient strategy of Moraxella to block the activation of complement and to inhibit C3a-mediated inflammation.
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| 42. |
- Hoffmann, Thomas J., et al.
(författare)
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Genome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Prostate-specific antigen (PSA) levels have been used for detection and surveillance of prostate cancer (PCa). However, factors other than PCa - such as genetics - can impact PSA. Here we present findings from a genome-wide association study (GWAS) of PSA in 28,503 Kaiser Permanente whites and 17,428 men from replication cohorts. We detect 40 genome-wide significant (P<5 × 10-8) single-nucleotide polymorphisms (SNPs): 19 novel, 15 previously identified for PSA (14 of which were also PCa-associated), and 6 previously identified for PCa only. Further analysis incorporating PCa cases suggests that at least half of the 40 SNPs are PSA-associated independent of PCa. The 40 SNPs explain 9.5% of PSA variation in non-Hispanic whites, and the remaining GWAS SNPs explain an additional 31.7%; this percentage is higher in younger men, supporting the genetic basis of PSA levels. These findings provide important information about genetic markers for PSA that may improve PCa screening, thereby reducing over-diagnosis and over-treatment.
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| 43. |
- Hutchinson, Peter J, et al.
(författare)
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Consensus statement from the 2014 International Microdialysis Forum
- 2015
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 41:9, s. 1517-1528
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Tidskriftsartikel (refereegranskat)abstract
- Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.
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| 44. |
- Jakovljevic, M., et al.
(författare)
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VDSL Power Back-Off Parameter Optimization for a Cable Bundle
- 2007
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Ingår i: Proceedings European Signal Processing Conference. - Poznan : Poznań University of Technology. - 9788392134022 - 9788392134046 ; , s. 550-554
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Konferensbidrag (refereegranskat)abstract
- To better utilize the capacity of the twisted-pair access networks, operators deploying very high-speed digital subscriber line (VDSL) systems need accurate parameters for power back-off (PBO). However, VDSL standards give almost no guidance on how these parameters should be established for a particular network. In this paper we present a new technique for optimizing PBO parameters for a cable bundle, which is based on the Nelder-Mead simplex search algorithm. In this way each operator can easily calculate PBO parameters that match its actual access network down to the individual cable bundle. Using the properties of the PBO, as defined in the VDSL standard, we show how a normalized FEXT coupling can replace the knowledge of the individual couplings during the optimization of the PBO parameters. By simulations based on measured cable data we show that our approach using cable bundle unique PBO (CUPBO) achieves a significant improvements compared to the performance achieved with the ordinary PBO. © 2007 EURASIP.
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| 45. |
- John Mukkattukavil, D., et al.
(författare)
-
Resonant inelastic soft x-ray scattering on LaPt 2 Si 2
- 2022
-
Ingår i: Journal of physics. Condensed matter : an Institute of Physics journal. - 1361-648X .- 0953-8984. ; 34:32
-
Tidskriftsartikel (refereegranskat)abstract
- X-ray absorption and resonant inelastic x-ray scattering spectra of LaPt2Si2single crystal at the Si 2pand La 4dedges are presented. The data are interpreted in terms of density functional theory, showing that the Si spectra can be described in terms of Sisanddlocal partial density of states (LPDOS), and the La spectra are due to quasi-atomic local 4fexcitations. Calculations show that Ptd-LPDOS dominates the occupied states, and a sharp localized Lafstate is found in the unoccupied states, in line with the observations.
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| 46. |
- Kamphuis, R., et al.
(författare)
-
Integrating demand flexibility with distributed generation - Renewable energy sources (DG-RES) at the residential household and commercial customer level in electricity grids
- 2017
-
Ingår i: CIRED - Open Access Proceedings Journal. - : Institution of Engineering and Technology. ; , s. 1827-1830
-
Konferensbidrag (refereegranskat)abstract
- Commercial and operational use of residential and commercial user demand-side flexibility in energy grids will play an important but, as yet, not disclosed role in realising the required increase in the penetration of DG-RES. An increased embedding potential is needed to satisfy ambitious energy efficiency and carbon dioxide emission targets. Introduction of smart technologies is seen as a facilitator but also encounters technological, operational, market and regulatory challenges. From assessing a number of technologies and field test projects, task 17 of the IEA/DSM program has explored the nature of this demand-side flexibility and the stakeholder context. It was found that a portfolio of services and control strategies for coordinating flexibility in an efficient, safe, reliable and scalable manner can be found. The boundary conditions, valuation and practical implementation are also discussed.
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| 47. |
- Karlsson, Maths, 1978, et al.
(författare)
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Alkali-ion concentration dependence of the structure of proton-conducting alkali thio-hydroxogermanates investigated with neutron diffraction
- 2015
-
Ingår i: Solid State Ionics. - : Elsevier BV. - 0167-2738. ; 274, s. 40-45
-
Tidskriftsartikel (refereegranskat)abstract
- The proton-conducting hydrated alkali thio-hydroxogermanate's MxGeSx(OH)(4) - x center dot yH(2)O (M = Na and K; x = 1 - 4,y approximate to 0.5 - 2) were investigated by means of neutron diffraction with the aim to elucidate how the structure changes as a function of alkali-ion concentration, x, type of alkali ion, M, and water content, y. For x = 1 - 3 we find that the materials are amorphous and composed of thio-hydroxogermanate anions, water molecules, and charge balancing alkali ions, whereas for x = 4 we find that the materials contain also a crystalline phase, suggesting that it is difficult to prepare purely amorphous materials for the highest alkali-ion concentration, for both the Na and K based materials. For x = 1 - 3, the structure is reflected by an intermediate-range ordering, with a characteristic length-scale ranging from approximately 6 to 9 angstrom, which is dependent on both x and M and which may be related to the separation distance between dimers of thio-hydroxogermanate anions. As x increases, the intermediate-range ordering shortens, possibly as the result of an increasing level of hydration water that may act as a dielectric medium that reduces the repulsive interaction between the negatively charged thio-hydroxogermanate anions and/or between the positively charged alkali ions. A comparison of the structural results to the reported conductivities of the same materials indicates a non-trivial relationship, which depends on both the type and concentration of alkali ions, as well as on the level of hydration water.
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| 48. |
- Kelly, D., et al.
(författare)
-
Improved screening of fall risk using free-living based accelerometer data
- 2022
-
Ingår i: Journal of Biomedical Informatics. - : Elsevier BV. - 1532-0464 .- 1532-0480. ; 131
-
Tidskriftsartikel (refereegranskat)abstract
- Falls are one of the most costly population health issues. Screening of older adults for fall risks can allow for earlier interventions and ultimately lead to better outcomes and reduced public health spending. This work proposes a solution to limitations in existing fall screening techniques by utilizing a hip-based accelerometer worn in free-living conditions. The work proposes techniques to extract fall risk features from periods of free-living ambulatory activity. Analysis of the proposed techniques is conducted and compared with existing screening methods using Functional Tests and Lab-based Gait Analysis. 1705 Older Adults from Umea (Sweden) were assessed. Data consisted of 1 Week of hip worn accelerometer data, gait measurements and performance metrics for 3 functional tests. Retrospective and Prospective fall data were also recorded based on the incidence of falls occurring 12 months before and after the study commencing respectively. Machine learning based experiments show accelerometer based measures perform best when predicting falls. Prospective falls had a sensitivity and specificity of 0.61 and 0.66 respectively while retrospective falls had a sensitivity and specificity of 0.61 and 0.68 respectively.
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| 49. |
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| 50. |
- Keskin, Isil, 1987-, et al.
(författare)
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The molecular pathogenesis of superoxide dismutase 1-linked ALS is promoted by low oxygen tension
- 2019
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Ingår i: Acta Neuropathologica. - New York : Springer. - 0001-6322 .- 1432-0533. ; 138:1, s. 85-101
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in superoxide dismutase 1 (SOD1) cause amyotrophic lateral sclerosis (ALS). Disease pathogenesis is linked to destabilization, disorder and aggregation of the SOD1 protein. However, the non-genetic factors that promote disorder and the subsequent aggregation of SOD1 have not been studied. Mainly located to the reducing cytosol, mature SOD1 contains an oxidized disulfide bond that is important for its stability. Since O2 is required for formation of the bond, we reasoned that low O2 tension might be a risk factor for the pathological changes associated with ALS development. By combining biochemical approaches in an extensive range of genetically distinct patient-derived cell lines, we show that the disulfide bond is an Achilles heel of the SOD1 protein. Culture of patient-derived fibroblasts, astrocytes, and induced pluripotent stem cell-derived mixed motor neuron and astrocyte cultures (MNACs) under low oxygen tensions caused reductive bond cleavage and increases in disordered SOD1. The effects were greatest in cells derived from patients carrying ALS-linked mutations in SOD1. However, significant increases also occurred in wild-type SOD1 in cultures derived from non-disease controls, and patients carrying mutations in other common ALS-linked genes. Compared to fibroblasts, MNACs showed far greater increases in SOD1 disorder and even aggregation of mutant SOD1s, in line with the vulnerability of the motor system to SOD1-mediated neurotoxicity. Our results show for the first time that O2 tension is a principal determinant of SOD1 stability in human patient-derived cells. Furthermore, we provide a mechanism by which non-genetic risk factors for ALS, such as aging and other conditions causing reduced vascular perfusion, could promote disease initiation and progression.
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