| 1. |
- Alvez, Maria Bueno, et al.
(författare)
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Next generation pan-cancer blood proteome profiling using proximity extension assay
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.
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| 2. |
- Bergquist, Filip, et al.
(författare)
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Pharmacokinetics of Intravenously (DIZ101), Subcutaneously (DIZ102), and Intestinally (LCIG) Infused Levodopa in Advanced Parkinson Disease
- 2022
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Ingår i: Neurology. - : Lippincott, Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 99:10, s. E965-E976
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Intestinal levodopa/carbidopa gel infusion (LCIG) is superior to oral treatment in advanced Parkinson disease. The primary objective of this trial was to investigate whether continuous subcutaneous or intravenous infusion with a continuously buffered acidic levodopa/carbidopa solution yields steady-state plasma concentrations of levodopa that are equivalent in magnitude, and noninferior in variability, to those obtained with LCIG in patients with advanced Parkinson disease. Methods A concentrated acidic levodopa/carbidopa (8:1) solution buffered continuously and administered intravenously (DIZ101) or subcutaneously (DIZ102) was compared with an approved LCIG in a randomized, 3-period crossover, open-label, multicenter trial. Formulations were infused for 16 hours to patients with Parkinson disease who were using LCIG as their regular treatment. Patients were recruited from several university neurology clinics but came to the same phase I unit for treatment. Pharmacokinetic variables and safety including dermal tolerance are reported. The primary outcomes were bioequivalence and noninferior variability of DIZ101 and DIZ102 vs LCIG with respect to levodopa plasma concentrations. Results With dosing adjusted to estimated bioavailability, DIZ101 and DIZ102 produced levodopa plasma levels within standard bioequivalence limits compared with LCIG in the 18 participants who received all treatments. Although the levodopa bioavailability for DIZ102 was complete, it was 80% for LCIG. Therapeutic concentrations of levodopa were reached as quickly with subcutaneous administration of DIZ102 as with LCIG and remained stable throughout the infusions. Owing to poor uptake of LCIG, carbidopa levels in plasma were higher with DIZ101 and DIZ102 than with the former. All individuals receiving any of the treatments (n = 20) were included in the evaluation of safety and tolerability. Reactions at the infusion sites were mild and transient. Discussion It is feasible to rapidly achieve high and stable levodopa concentrations by means of continuous buffering of a subcutaneously administered acidic levodopa/carbidopa-containing solution.
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| 3. |
- Boissin, Constance, et al.
(författare)
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Development and evaluation of deep learning algorithms for assessment of acute burns and the need for surgery
- 2023
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of burn extent and depth are critical and require very specialized diagnosis. Automated image-based algorithms could assist in performing wound detection and classification. We aimed to develop two deep-learning algorithms that respectively identify burns, and classify whether they require surgery. An additional aim assessed the performances in different Fitzpatrick skin types. Annotated burn (n = 1105) and background (n = 536) images were collected. Using a commercially available platform for deep learning algorithms, two models were trained and validated on 70% of the images and tested on the remaining 30%. Accuracy was measured for each image using the percentage of wound area correctly identified and F1 scores for the wound identifier; and area under the receiver operating characteristic (AUC) curve, sensitivity, and specificity for the wound classifier. The wound identifier algorithm detected an average of 87.2% of the wound areas accurately in the test set. For the wound classifier algorithm, the AUC was 0.885. The wound identifier algorithm was more accurate in patients with darker skin types; the wound classifier was more accurate in patients with lighter skin types. To conclude, image-based algorithms can support the assessment of acute burns with relatively good accuracy although larger and different datasets are needed.
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| 4. |
- Bornehag, Carl-Gustaf, 1957-, et al.
(författare)
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The SELMA study : a birth cohort study in Sweden following more than 2000 mother-child pairs
- 2012
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Ingår i: Paediatric and Perinatal Epidemiology. - Hoboken, USA : Wiley-Blackwell. - 0269-5022 .- 1365-3016. ; 26:5, s. 456-467
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Tidskriftsartikel (refereegranskat)abstract
- Background: This paper describes the background, aim and study design for the Swedish SELMA study that aimed to investigate the importance of early life exposure during pregnancy and infancy to environmental factors with a major focus on endocrine disrupting chemicals for multiple chronic diseases/disorders in offspring.Methods: The cohort was established by recruiting women in the 10th week of pregnancy. Blood and urine from the pregnant women and the child and air and dust from home environment from pregnancy and infancy period have been collected. Questionnaires were used to collect information on life styles, socio-economic status, living conditions, diet and medical history.Results: Of the 8394 reported pregnant women, 6658 were invited to participate in the study. Among the invited women, 2582 (39%) agreed to participate. Of the 4076 (61%) non-participants, 2091 women were invited to a non-respondent questionnaire in order to examine possible selection bias. We found a self-selection bias in the established cohort when compared with the non-participant group, e.g. participating families did smoke less (14% vs. 19%), had more frequent asthma and allergy symptoms in the family (58% vs. 38%), as well as higher education among the mothers (51% vs. 36%) and more often lived in single-family houses (67% vs. 60%).Conclusions: These findings indicate that the participating families do not fully represent the study population and thus, the exposure in this population. However, there is no obvious reason that this selection bias will have an impact on identification of environmental risk factors.
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| 5. |
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| 6. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 7. |
- Geijer Lundin, Erik, et al.
(författare)
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Adaptive Filtering Applied to an Uplink Load Estimate in WCDMA
- 2003
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Ingår i: Proceedings of the 57th IEEE Semiannual Vehicular Technology Conference. - Linköping : Linköping University Electronic Press. - 0780377575 ; , s. 452-456
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Konferensbidrag (refereegranskat)abstract
- In the uplink of a WCDMA system, a natural choice of resource quantity is the uplink noise rise, i.e., total received power over noise power. Unfortunately this quantity is hard to measure and estimates are often noisy. This paper focuses on relative load which is closely related to the noise rise. Model-based signal processing with change detection techniques is herein used to suppress noise and minor oscillations while being alert on fast load changes. The time varying model identified in the process can also be used for prediction of future values, something which resource management algorithms can benefit from.
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| 8. |
- Geijer Lundin, Erik, et al.
(författare)
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Robust Uplink Resource Allocation in CDMA Cellular Radio Systems
- 2005
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Ingår i: Proceedings of the 44th IEEE Conference on Decision and Control and European Control Conference 2005. - Linköping : Linköping University Electronic Press. - 0780395670 ; , s. 1848-1853
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Konferensbidrag (refereegranskat)abstract
- Radio resource management (RRM) in cellular radio system is an example of automatic control. The system performance may be increased by introducing decentralization, shorter delays and increased adaptation to local demands. However, it is hard to guarantee system stability without being, too conservative while using decentralized resource management. In this paper, two algorithms that both guarantee system stability and use local resource control are proposed for the uplink (mobile to base station). While one of the algorithms uses only local decisions, the other uses a central node to coordinate resources among different local nodes. In the chosen design approach, a feasible solution to the optimization problems corresponds to a stable system. Therefore, the algorithms will never assign resources that lead to an unstable system. Simulations indicate that the proposed algorithms also provide high capacity at any given uplink load level.
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| 9. |
- Geijer Lundin, Erik, et al.
(författare)
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Uplink Load Estimates in WCDMA with Different Availability of Measurements
- 2003
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Ingår i: Proceedings of the 57th IEEE Semiannual Vehicular Technology Conference. - Linköping : Linköping University Electronic Press. - 0780377575 ; , s. 1198-1202 vol.2
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Konferensbidrag (refereegranskat)abstract
- In the uplink of a WCDMA system, a natural choice of resource management control quantity is the uplink noise rise, i.e., total received power over noise power. Unfortunately this quantity is hard to measure. In this paper, we propose and evaluate a number of noise rise estimates which all rely on path gain measurements. These measurements can be made available either periodically or event-driven as described in 3GPP (Release 99). Simulations show that event-driven measurements yield comparable performance to periodic measurements, but with much fewer measurement reports. Despite severely limited path gain knowledge due to that some users report to another RNC, we still manage to estimate the uplink noise rise reasonably well.
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| 10. |
- Geijer Lundin, Erik, et al.
(författare)
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Uplink Load Estimation in WCDMA
- 2003
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Ingår i: Proceedings of the 2003 IEEE Wireless Communications and Networking. - 0780377001 ; , s. 1669-1674 vol.3
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Konferensbidrag (refereegranskat)abstract
- All cellular radio systems have radio resource management algorithms which rely on some sort of resource quantity. In the uplink of a WCDMA system, a natural choice of such a quantity is the uplink noise rise, i.e., total received power over noise power. Unfortunately this quantity is hard to measure. In this paper, we propose and evaluate four different noise rise 711 estimates. The best performing estimate provides an average error of less than 1 dB for practical load levels. Due to low standard deviation of single estimates it is possible to apply a simple error correction algorithm.
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| 11. |
- Geijer Lundin, Erik
(författare)
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Uplink Load in CDMA Cellular Systems
- 2003
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cellular mobile systems designed to handle multimedia services are currently being developed. The primary goal for any mobile system is to provide a satisfactory quality of service, both to operators and customers. Providing good quality of service while maintaining system stability requires accurate knowledge of the system load. In particular, it is important to be able to predict how a resource management decision will affect the stability of the network. This thesis addresses the problem of characterizing and estimating the uplink load in a cellular system using CDMA (Code Division Multiple Access) in the radio interface.Uplink load can be related directly to the uplink power control problem of finding transmitter powers to support the users' quality of service requirements. This yields a rather theoretical view. Another way of looking at uplink load is to relate it to the total received power users induce in the base station antennas. Both of these views are handled and relations between them are established in this thesis.The literature survey on uplink load provided in this work concludes that practical estimates of the uplink load are generally what can be referred to as decentralized estimates; they use information gathered only in the immediate vicinity of the estimates' host node. As an alternative to these estimates, a number of centralized estimates based on information readilyavailable to the system are proposed. The usage of information from several cells makes them more sensitive to the soft capacity inherent in all CDMA cellular systems.Extensive simulations in an advanced WCDMA (Wideband Code Division Multiple Access) simulator show that the estimates statistically perform well and the performance is insensitive to non uniform traffic load.In the time domain, the load approximation can be described as oscillations superimposed on a slowly varying bias. If occasional high loads can be accepted, a non-oscillative signal representing the uplink load can be used to further increase the utilization of the resources. An algorithm is proposed to estimate the bias and a prediction of it.
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| 12. |
- Gunnarsson, Fredrik, et al.
(författare)
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Uplink Load and Link Budget with Stochastic Noise Rise Levels in CDMA Cellular Systems
- 2005
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Ingår i: Proceedings of Radiovetenskap och Kommunikation 2005. ; , s. 491-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The limiting factor in the uplink of all CDMA cellular systems is the relation between uplink noise rise and intended coverage. In link budgets, noise rise is usually simply handled as a constant contribution to the background noise in logarithmic scale, often referred to as interference margin. In practice, however, it is not constant. We model the uplink noise rise as a lognormal distribution, and investigate the impact to link budgets. Simulations and numerical calculations show that the uplink noise rise variance does not critically affect the uplink capacity and coverage. System feasibility and its relation to the uplink load is also discussed. It is shown that approximative load expressions provides an upper bound on the uplink load and therefore they can be used to imply system feasibility. Furthermore, the uplink load expressions provide accurate approximations of the load given that the load is within the practical limits given by the link budgets.
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| 13. |
- Gustafsson, Fredrik, et al.
(författare)
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Transmission Timing - A Control Approach to Distributed Uplink Scheduling in WCDMA
- 2004
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Ingår i: Proceedings of Reglermöte 2004. - Linköping : Linköping University Electronic Press. ; , s. 1667-1672 vol.2
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Centralized control and coordination of the connections in a wireless network is not possible in practice. To keep the delay from measure-ment instants to actuating the decisions, distributed control is required. This paper focuses on the uplink (from mobiles to base stations) and dis-cusses distributing the decision of when and when not to transmit data (distributed scheduling) to the mobiles. The scheme, uplink transmission timing, utilizes mobile transmitter power control feedback from the base station receiver to determine whether the channel is favorable or not compared to the average channel condition. Thereby, the battery consumption and disturbing power to other connections are reduced. The algorithm can be described as a feedback control system. Some transient behaviors are analyzed using systems theory, and supported by wireless network simulations of a system with a WCDMA (Wideband Code Division Multiple Access) radio interface as in most 3G systems.
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| 14. |
- Gustafsson, Fredrik, et al.
(författare)
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Uplink Load and Link Budget with Stochastic Noise Rise Levels in CDMA Cellular Systems
- 2004
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The limiting factor in the uplink of all CDMA cellular systems is the relation between uplink noise rise and intended coverage. In link budgets, noise rise is usually simply handled as a constant contribution to the background noise in logarithmic scale, often referred to as interference margin. In practice, however, it is not constant. We model the uplink noise rise as a lognormal distribution, and investigate the impact to link budgets. Simulations and numerical calculations show that the uplink noise rise variance does not critically affect the uplink capacity and coverage. System feasibility and its relation to the uplink load is also discussed. It is shown that approximative load expressions provides an upper bound on the uplink load and therefore they can be used to imply system feasibility. Furthermore, the uplink load expressions provide accurate approximations of the load given that the load is within the practical limits given by the link budgets.
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| 15. |
- Gustafsson, Fredrik, et al.
(författare)
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Uplink Load Estimation in WCDMA
- 2002
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Ingår i: Proceedings of Radiovetenskap och Kommunikation 2002. - Linköping : Linköping University Electronic Press.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- All cellular radio systems depend on well performing radio resource management algorithms to efficiently utilize available resources. These algorithms make their decisions based on some sort of resource quantity. In the uplink of a WCDMA system, the total received power at the base stations is a natural choice of such a quantity. Unfortunately this quantity cannot be measured with enough accuracy to be used by resource management algorithms. One way of getting around this problem is to estimate a closely related quantity, namely the uplink noise rise. In this paper, we propose and evaluate four different methods to estimate the noise rise. The estimates are insensitive to users bit rate and use data readily available in the system. The best performing method estimates, on average, the uplink noise rise with an error of less than 1 dB for practical load scenarios.
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| 16. |
- Håkansson, Irene, et al.
(författare)
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Successful autologous haematopoietic stem cell transplantation for refractory myasthenia gravis - a case report
- 2017
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Ingår i: Neuromuscular Disorders. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0960-8966 .- 1873-2364. ; 27:1, s. 90-93
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Tidskriftsartikel (refereegranskat)abstract
- Myasthenia gravis (MG) is an autoimmune disease, with immune reactivity against the post-synaptic endplate of the neuromuscular junction. Apart from symptomatic treatment with choline esterase blockers, many patients also require immunomodulatory treatment. Despite existing treatment options, some patients are treatment refractory. We describe a patient with severe MG refractory to corticosteroids, four oral immunosuppressants, cyclophosphamide, rituximab and bortezomib who was treated with autologous haematopoietic stem cell transplantation. Two years after this, the patient has significantly improved in objective tests and in quality of life and leads an active life. Diplopia is her only remaining symptom and she is completely free of medication for MG. We believe that autologous haematopoietic stem cell transplantation can be an effective therapeutic option for carefully selected cases of severe, treatment refractory MG. (c) 2016 Elsevier B.V. All rights reserved.
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| 17. |
- Pereira Filho, Antonio J. G., et al.
(författare)
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Impact of Ankle Brachial Index Calculations on Peripheral Arterial Disease Prevalence and as a Predictor of Cardiovascular Risk
- 2022
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier. - 1078-5884 .- 1532-2165. ; 64:2-3, s. 217-224
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to estimate the prevalence and predictive accuracy for cardiovascular (CV) morbidity by using different ankle brachial index (ABI) calculation methods in the general population.Methods: ABI measurements and questionnaire data were collected from 5 080 randomly selected citizens aged 60 - 90 years. A 10 year follow up with data from Swedish national health registries was carried out. ABI was calculated using as numerator the highest (ABI-HI) or the lowest (ABI-LO) ankle BP obtained in each leg. Subjects were defined as references or having peripheral arterial disease (PAD) based on ABI-LO (Group 1) or ABI-HI (Group 2). Prevalence, mortality, CV events and risk were then analysed for these three groups, and their predictive power by using the area under the curve (AUC).Results: A total of 4 909 inhabitants were included in the cohort (References: 83.8%, Group 1: 6.7% and Group 2: 9.6%). The prevalence of PAD was 16% using ABI-LO, and 9.6% using ABI-HI. The 10 year all cause mortality for references and Groups 1 and 2 was 27.6%, 48.8%, and 67.2%, respectively. The overall age adjusted hazard ratio (95% confidence interval) for the composite outcome of CV mortality and a non-fatal CV event was 1.25 (1.06 - 1.49) for Group 1 and 2.11 (1.85 - 2.39) for Group 2. The prediction accuracy for ABI < 0.9 in predicting CV event measured with AUC was 0.60 for ABI-HI and 0.62 for ABI-LO.Conclusion: An ABI < 0.9 should be considered a strong risk marker for future CV morbidity. Applying the traditional ABI calculation method of using the highest measured ankle BP, a group of subjects with high CV risk may be overlooked for intervention, and this why the lowest ankle BP should be the preferred for risk stratification. However, as a single predictive tool an ABI < 0.9 cannot adequately discriminate which individual will have a future CV event regardless of calculation method used.
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| 18. |
- Petersson, Malin, et al.
(författare)
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Patient-reported symptom severity in a nationwide myasthenia gravis cohort : cross-sectional analysis of the Swedish GEMG study
- 2021
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 97:14, s. e1382-e1391
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: To describe myasthenia gravis activities of daily living (MG-ADL) in relation to clinical characteristics in a large Swedish nationwide cohort.Methods: In a cross-sectional prevalence cohort study, the Genes and Environment in Myasthenia Gravis study, performed from November 2018 through August 2019, patients with myasthenia gravis (MG) were invited to submit an extensive 106-item life environment questionnaire, including the MG-ADL score. Patients were classified into early-onset MG (EOMG, <50 years), late-onset MG (LOMG, >= 50 years), or thymoma-associated MG (TAMG). Comparisons of disease-specific characteristics were made between subgroups, sexes, and different MG-ADL scores.Results: A total of 1,077 patients were included, yielding a 74% response rate: 505 (47%) were classified as EOMG, 520 (48%) LOMG, and 45 (4%) TAMG. Mean age at inclusion was 64.3 years (SD 15.7) and mean disease duration was 14.6 years (SD 14.0). Complete MG-ADL scores (n = 1,035) ranged from 0p to 18p, where 26% reported a score of 0p. Higher MG-ADL scores were associated with female sex, obesity, and diagnostic delay (odds ratio [OR] 1.62, 1.72, and 1.69; p(adj) = 0.017, 0.013, and 0.008) and inversely correlated with high educational attainment (OR 0.59; p(adj) = 0.02), but not with age at inclusion, disease subtype, or disease duration. Almost half of the population (47%) reported MG-ADL >= 3p, corresponding to an unsatisfactory symptom state.Discussion: In this nationwide study, comprising more than 40% of the prevalent MG population in Sweden, almost half of the patients reported current disease symptoms associated with an unsatisfactory symptom state, indicating the need for improved treatment options.
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| 19. |
- Sartipy, Fredrik, et al.
(författare)
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Cardiovascular long-term outcome and prophylactic treatment patterns in peripheral arterial disease in a population-based cohort
- 2019
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Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - : OXFORD UNIV PRESS. - 2058-5225 .- 2058-1742. ; 5:4, s. 310-320
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This study evaluates 10-year follow-up data on associated comorbidity, mortality, and pharmacological treatment patterns for men and women with different stages of peripheral arterial disease (PAD) in a population-based setting.Methods and results: This was a prospective observational population-based cohort study, based on physical examinations and questionnaires at baseline supplemented with national register data between 2005 and 2015. Subjects were placed in subgroups defined by ankle-brachial index levels and reported symptoms; asymptomatic PAD (APAD), intermittent claudication (IC), severe limb ischaemia (SLI), or references (Ref). Cox proportional hazards regression models were used for analysis with adjustments for sex and baseline age and comorbidity. The cohort consisted of 5080 subjects (45% males). At baseline, APAD, IC, and SLI were prevalent in 559 (11%), 320 (6.3%), and 78 (1.5%) subjects, respectively. A significant increased risk for cardiovascular (CV) death, even when adjusted for age and baseline morbidity, were noted in all PAD stages as compared with reference group with a small difference between APAD and IC, an adjusted hazard ratio 1.80 (confidence interval 1.45-2.22) and 1.95 (1.50-2.53), respectively. Only about 60% of PAD subjects received medical prophylactic treatment as recommended in guidelines.Conclusion: Peripheral arterial disease subjects had significantly increased CV morbidity and mortality risks, especially males. Asymptomatic PAD subjects confer similar risk for CV events as symptomatic patients. Our findings motivate enhanced preventive efforts of all PAD stages, including in asymptomatic disease.
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| 20. |
- Sartipy, Fredrik, et al.
(författare)
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Presence of asymptomatic Peripheral Arterial Disease in combination with common risk factors elevates the cardiovascular risk Substantially
- 2022
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Ingår i: INTERNATIONAL JOURNAL OF CARDIOLOGY CARDIOVASCULAR RISK AND PREVENTION. - Philadelphia, PA, United States : Elsevier. - 2772-4875. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: This study evaluates the risks for adverse cardiovascular (CV) events in Asymptomatic Peripheral Arterial Disease (APAD) combined with different traditional CV risk factors. Methods: A population-based observational study of 8000 subjects, identified 559 subjects as having APAD through ankle-brachial index (ABI) measurements and questionnaires regarding limb symptoms. This cohort and subgroups classified by presence of different traditional CV risk factors at baseline were assessed for 10 years on CV outcome. The recorded endpoints were all-cause mortality, CV mortality and non-fatal CV events. Results: Before subdividing the APAD subjects, the CV mortality incidence was 28.5 deaths per 1000 person-years as compared to 8.7 deaths for references without APAD. For subjects with hypertension at baseline the CV mortality incidence was 35.4 when combined with APAD and 11.7 without. In women with hypertension but without other risk factors, presence of APAD increased the age-adjusted Hazard Ratio (HR) for fatal and non-fatal CV events by 1.86 [CI 1.54,2.24, p < 0.001]. Conclusions: ABI measurements should be considered an important indication for aggressive multifactorial risk factor reduction in populations with any other prevalent CV risk factor. In hypertension, diabetes mellitus and a smoking history, coexisting APAD contributes significantly to the increased age-adjusted CV risk.
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| 21. |
- Sartipy, Fredrik, et al.
(författare)
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Ten Year Mortality in Different Peripheral Arterial Disease Stages : A Population Based Observational Study on Outcome
- 2018
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : W B SAUNDERS CO LTD. - 1078-5884 .- 1532-2165. ; 55:4, s. 529-536
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to determine long-term mortality rates and the underlying cause of death for subjects with different peripheral arterial disease (PAD) stages in a population based setting. Methods: A randomly selected population sample of 5080 subjects was enrolled in the study in 2004-2005. Participants completed health state questionnaires and underwent ankle brachial index (ABI) measurements for classification into PAD severity stages and reference subjects. A follow-up was conducted by the end of 2015 using data from Swedish governmental national registers for cause of death, which was then compared with PAD stage determined at baseline in 2005. Results: The 10 year all cause mortality was 27% for reference cases, 56% for asymptomatic PAD (APAD), 63% for intermittent claudication (IC), and 75% for severe limb ischaemia (SLI). Among all PAD subjects, cardiovascular (CV) causes were the most common main cause of death (45%) and a CV event was present as either the main or one of the three most common contributing causes of death in 64% of the cases. The age adjusted hazard ratios for a main cause of death by a CV event were 1.9 (95% CI 1.5-2.3) for APAD, 2.6 (95% CI 2.1-3.4) for IC, and 3.5 (95% CI 2.3-5.2) for SLI. Conclusion: PAD subjects, including the APAD subjects, are still at high risk of CV death. The mortality risks are more than doubled in symptomatic PAD patients compared with reference subjects and increase by severity of PAD stage. Awareness and improved risk reduction management of PAD are still warranted.
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| 22. |
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| 23. |
- Al-Minawi, Ali Z., et al.
(författare)
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The ERCC1/XPF endonuclease is required for completion of homologous recombination at DNA replication forks stalled by inter-strand cross-links
- 2009
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 37:19, s. 6400-6413
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Tidskriftsartikel (refereegranskat)abstract
- Both the ERCC1-XPF complex and the proteins involved in homoIogous recombination (HR) have critical roles in inter-strand cross-link (ICL) repair. Here, we report that mitomycin C-induced lesions inhibit replication fork elongation. Furthermore, mitomycin C-induced DNA double-strand breaks (DSBs) are the result of the collapse of ICL-stalled replication forks. These are not formed through replication run off, as we show that mitomycin C or cisplatin-induced DNA lesions are not incised by global genome nucleotide excision repair (GGR). We also suggest that ICL-lesion repair is initiated either by replication or transcription, as the GGR does not incise ICL-lesions. Furthermore, we report that RAD51 foci are induced by cisplatin or mitomycin C independently of ERCC1, but that mitomycin C-induced HR measured in a reporter construct is impaired in ERCC1-defective cells. These data suggest that ERCC1-XPF plays a role in completion of HR in ICL repair. We also find no additional sensitivity to cisplatin by siRNA co-depletion of XRCC3 and ERCC1, showing that the two proteins act on the same pathway to promote survival.
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| 24. |
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| 25. |
- Arne, Mats, 1954-, et al.
(författare)
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Factors associated with good self-rated health and quality of life in subjects with self-reported COPD
- 2011
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - 1176-9106 .- 1178-2005. ; 6, s. 511-519
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent guidelines for chronic obstructive pulmonary disease (COPD) state that COPD is both preventable and treatable. To gain a more positive outlook on the disease it is interesting to investigate factors associated with good, self-rated health and quality of life in subjects with self-reported COPD in the population. Methods: In a cross-sectional study design, postal survey questionnaires were sent to a stratified, random population in Sweden in 2004 and 2008. The prevalence of subjects (40–84 years) who reported having COPD was 2.1% in 2004 and 2.7% in 2008. Data were analyzed for 1475 subjects. Regression models were used to analyze the associations between health measures (general health status, the General Health Questionnaire, the EuroQol five-dimension questionnaire) and influencing factors. Results: The most important factor associated with good, self-rated health and quality of life was level of physical activity. Odds ratios for general health varied from 2.4 to 7.7 depending on degree of physical activity, where subjects with the highest physical activity level reported the best health and also highest quality of life. Social support and absence of economic problems almost doubled the odds ratios for better health and quality of life. Conclusions: In this population-based public health survey, better self-rated health status and quality of life in subjects with self-reported COPD was associated with higher levels of physical activity, social support, and absence of economic problems. The findings indicated that of possible factors that could be influenced, promoting physical activity and strengthening social support are important in maintaining or improving the health and quality of life in subjects with COPD. Severity of the disease as a possible confounding effect should be investigated in future population studies.
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| 26. |
- Aurelius, Oskar, et al.
(författare)
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The Crystal Structure of Thermotoga maritima Class III Ribonucleotide Reductase Lacks a Radical Cysteine Pre-Positioned in the Active Site
- 2015
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides to deoxyribonucleotides, the building blocks for DNA synthesis, and are found in all but a few organisms. RNRs use radical chemistry to catalyze the reduction reaction. Despite RNR having evolved several mechanisms for generation of different kinds of essential radicals across a large evolutionary time frame, this initial radical is normally always channelled to a strictly conserved cysteine residue directly adjacent to the substrate for initiation of substrate reduction, and this cysteine has been found in the structures of all RNRs solved to date. We present the crystal structure of an anaerobic RNR from the extreme thermophile Thermotoga maritima (tmNrdD), alone and in several complexes, including with the allosteric effector dATP and its cognate substrate CTP. In the crystal structure of the enzyme as purified, tmNrdD lacks a cysteine for radical transfer to the substrate pre-positioned in the active site. Nevertheless activity assays using anaerobic cell extracts from T. maritima demonstrate that the class III RNR is enzymatically active. Other genetic and microbiological evidence is summarized indicating that the enzyme is important for T. maritima. Mutation of either of two cysteine residues in a disordered loop far from the active site results in inactive enzyme. We discuss the possible mechanisms for radical initiation of substrate reduction given the collected evidence from the crystal structure, our activity assays and other published work. Taken together, the results suggest either that initiation of substrate reduction may involve unprecedented conformational changes in the enzyme to bring one of these cysteine residues to the expected position, or that alternative routes for initiation of the RNR reduction reaction may exist. Finally, we present a phylogenetic analysis showing that the structure of tmNrdD is representative of a new RNR subclass IIIh, present in all Thermotoga species plus a wider group of bacteria from the distantly related phyla Firmicutes, Bacteroidetes and Proteobacteria.
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| 27. |
- Ausen, Dag, et al.
(författare)
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Foresight Biomedical Sensors
- 2007
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The foresight study on biomedical sensors has addressed different approaches with future use of biomedical sensors in the health care sector, like: How will biomedical sensors shape the healthcare systems of the future? How can they impact the quality and cost of healthcare and what are the business opportunities in the Nordic region?
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| 28. |
- Axell, Erik, et al.
(författare)
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Coexistence of Speech and Best Effort Services in Enhanced Uplink WCDMA
- 2005
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Ingår i: in Proc. of Radiovetenskap och Kommunikation (RVK).
-
Konferensbidrag (refereegranskat)abstract
- An evaluation of the performance of coexistent voice and best effort data users in Enhanced Uplink WCDMA is studied in this paper. The main focus is on deriving the capacity regions and compare with previous WCDMA releases. It is shown that the Enhanced Uplink yields a large capacity gain in many aspects for all fractions of voice users compared to previous WCDMA releases. It is also shown, by the cumulative distribution functions of noise rise at the capacity limits, that the best effort data users experience bad quality at lower noise rise than voice users. This means that the capacity is in fact limited by the best effort users.
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| 29. |
- Barabash, Stas, et al.
(författare)
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Mars Orbiting Plasma Surveyor (MOPS)
- 2006
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Ingår i: Proceedings of the 6th IAA International Conference on Low-Cost Planetary Missions. ; , s. 227-232
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Mars Orbiting Plasma Surveyor (MOPS) is a microsatellite mission focused on studies of the near -Mars environment and the planet - solar wind interaction. The recent findings by the ESA Mars Express mission further highlighted the complexity of the processes taking place at the planet resulting from the solar wind interaction that strongly affect the planet's atmosphere. However, despite many previous Martian missions carrying different types of space plasma experiments, a comprehensive investigation including simultaneous measurements of particles, fields, and waves has never been performed. We consider a spinning spacecraft of a wet mass of 76.1 kg with a 9.7 kg payload, which can “hitchhike” on another platform until Mars orbit insertion, and then be released into a suitable orbit. The spacecraft design is based on the experience gained in very successful Swedish space plasma missions, Viking, Freja, Astrid-1, and Astrid-2. In the present mission design, the MOPS spacecraft is equipped with its own 1m high gain antenna for direct communication with the Earth. The payload includes a wave experiment with wire booms, magnetometer with a rigid boom, Langmuir probes, electron and ion energy spectrometers and an ion mass analyzer. An energetic neutral atom imager and an UV photometer may complete the core payload. One of the proposed scenarios is piggy - backing on the Russian Phobos - Grunt mission to be launched to Mars in 2011.
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| 30. |
- Behboudi, A, et al.
(författare)
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Functional significance of absence : The chromosomal segment harboring the Tp53 gene is missing in the T55 rat radiation hybrid mapping panel
- 2002
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Ingår i: Genomics. - : Academic Press. - 0888-7543 .- 1089-8646. ; 79:6, s. 844-848
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Tidskriftsartikel (refereegranskat)abstract
- The T55 rat radiation hybrid (RH) mapping panel has been reported to retain the entire rat genome at retention frequencies between 22% and 37%. However, we found that a small segment of rat chromosome 10 harboring at least four different genes, including Tp53, was completely absent from the panel (retention frequency = 0%). Two other markers located in the vicinity exhibited much reduced retention (2–6%). RH clones are generated by transferring highly fragmented DNA into a recipient cell. There might be a strong selection against the transfer and retention of chromosome segments harboring an intact Tp53, as the action of this gene might prevent proliferation and establishment of the RH clone. Our finding further suggests that unexpected low retention or absence of chromosome segments in an RH panel may represent indications that the segments harbor genes with important functions in cell proliferation control.
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| 31. |
- Behboudi, Afrouz, 1967, et al.
(författare)
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The functional significance of absence: the chromosomal segment harboring Tp53 is absent from the T55 rat radiation hybrid mapping panel.
- 2002
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 79:6, s. 844-8
-
Tidskriftsartikel (refereegranskat)abstract
- The T55 rat radiation hybrid (RH) mapping panel has been reported to retain the entire rat genome at retention frequencies between 22% and 37%. However, we found that a small segment of rat chromosome 10 harboring at least four different genes, including Tp53, was completely absent from the panel (retention frequency = 0%). Two other markers located in the vicinity exhibited much reduced retention (2-6%). RH clones are generated by transferring highly fragmented DNA into a recipient cell. There might be a strong selection against the transfer and retention of chromosome segments harboring an intact Tp53, as the action of this gene might prevent proliferation and establishment of the RH clone. Our finding further suggests that unexpected low retention or absence of chromosome segments in an RH panel may represent indications that the segments harbor genes with important functions in cell proliferation control.
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| 32. |
- Berglund, Sara, et al.
(författare)
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‘I had to leave’. A cultural analysis of motives for commercial transplantations.
- 2012
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Ingår i: The body as gift, resource and commodity. ; , s. 321-343
-
Bokkapitel (refereegranskat)abstract
- The article is based on a pilot study of the stories of Swedish patients having had a kidney transplant abroad. Our focus is on how people who have been transplanted abroad talk about and handles the dilemma that may arise due to the transplantation trips.
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| 33. |
- Bergquist, Filip, 1970, et al.
(författare)
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Motor Efficacy of Subcutaneous DIZ102, Intravenous DIZ101 or Intestinal Levodopa/Carbidopa Infusion
- 2024
-
Ingår i: MOVEMENT DISORDERS CLINICAL PRACTICE. - : WILEY. - 2330-1619.
-
Tidskriftsartikel (refereegranskat)abstract
- Background: It has been suggested that carbidopa at high blood concentrations may counter the therapeutic effect of levodopa in Parkinson's disease by entering the brain and blocking central levodopa conversion to dopamine. We previously demonstrated equivalent plasma levodopa concentration in patients with Parkinson's disease during 16 h of (1) intravenous carbidopa/levodopa (DIZ101) infusion, (2) subcutaneous carbidopa/levodopa (DIZ102) infusion or (3) intestinal carbidopa/levodopa gel infusion. Plasma levels of carbidopa were however approximately four times higher with DIZ101 and DIZ102 than with LCIG, and higher than those usually observed with oral levodopa/carbidopa. Objectives: To investigate if high carbidopa blood concentrations obtained with parenteral levodopa/carbidopa (ratio 8:1) counter the effect of levodopa on motor symptoms. Methods: Eighteen patients with advanced Parkinson's disease were administered DIZ101, DIZ102, and intestinal levodopa/carbidopa gel for 16 h on different days in randomized order. Video recordings of a subset of the motor examination in the Unified Parkinson's Disease Rating Scale (UPDRS) were evaluated by raters blinded for treatment and time. Motor function was also measured using a wrist-worn device monitoring bradykinesia, dyskinesia, and tremor (Parkinson KinetiGraph). Results: There was no tendency for poorer levodopa effect with DIZ101 or DIZ102 as compared to LCIG. Conclusion: Although DIZ101 or DIZ102 causes approximately four times higher plasma carbidopa levels than LCIG, patients responded equally well to all treatments. The results do not indicate that high plasma carbidopa levels hamper the motor efficacy of levodopa.
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| 34. |
- Bertz, Fredrik, et al.
(författare)
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Transformative Lifestyle Change: key to sustainable weight loss among women in a post-partum diet and exercise intervention
- 2015
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Ingår i: Maternal and Child Nutrition. - : Wiley. - 1740-8695 .- 1740-8709. ; 11:4, s. 631-645
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Tidskriftsartikel (refereegranskat)abstract
- The increase in overweight and obesity among women is a growing concern, and reproduction is associated with persistent weight gain. We have shown that dietary behavioural modification treatment, with or without exercise, results in weight loss and maintenance of weight loss. The aim of this study was to provide an explanatory model of how overweight and obese women achieve weight loss during, and after, participating in a post-partum diet and/or exercise intervention. Using Grounded Theory, we performed and analysed 29 interviews with 21 women in a 12-week Swedish post-partum lifestyle intervention with a 9-month follow-up. Interviews were made after the intervention and at the 9-month follow-up. To overcome initial barriers to weight loss, the women needed a ‘Catalytic Interaction’ (CI) from the care provider. It depended on individualised, concrete, specific and useful information, and an emotional bond through joint commitment, trust and accountability. Weight loss was underpinned by gradual introduction of conventional health behaviours. However, the implementation depended on the experience of the core category process ‘Transformative Lifestyle Change’ (TLC). This developed through a transformative process of reciprocal changes in cognitions, emotions, body, environment, behaviours and perceived self. Women accomplishing the stages of the TLC process were successful in weight loss, in contrast to those who did not. The TLC process, dependent on initiation through CI, led to implementation and integration of recognised health behaviours, resulting in sustainable weight loss. The TLC model, including the CI construct and definition of barriers, facilitators and strategies provides an explanatory model of this process.
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| 35. |
- Bivik, Caroline, et al.
(författare)
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Novel Genes Involved in Controlling Specification of Drosophila FMRFamide Neuropeptide Cells
- 2015
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Ingår i: Genetics. - : Genetics Society of America. - 0016-6731 .- 1943-2631. ; 200:4, s. 1229-1244
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Tidskriftsartikel (refereegranskat)abstract
- The expression of neuropeptides is often extremely restricted in the nervous system, making them powerful markers for addressing cell specification . In the developing Drosophila ventral nerve cord, only six cells, the Ap4 neurons, of some 10,000 neurons, express the neuropeptide FMRFamide (FMRFa). Each Ap4/FMRFa neuron is the last-born cell generated by an identifiable and well-studied progenitor cell, neuroblast 5-6 (NB5-6T). The restricted expression of FMRFa and the wealth of information regarding its gene regulation and Ap4 neuron specification makes FMRFa a valuable readout for addressing many aspects of neural development, i.e., spatial and temporal patterning cues, cell cycle control, cell specification, axon transport, and retrograde signaling. To this end, we have conducted a forward genetic screen utilizing an Ap4-specific FMRFa-eGFP transgenic reporter as our readout. A total of 9781 EMS-mutated chromosomes were screened for perturbations in FMRFa-eGFP expression, and 611 mutants were identified. Seventy-nine of the strongest mutants were mapped down to the affected gene by deficiency mapping or whole-genome sequencing. We isolated novel alleles for previously known FMRFa regulators, confirming the validity of the screen. In addition, we identified novel essential genes, including several with previously undefined functions in neural development. Our identification of genes affecting most major steps required for successful terminal differentiation of Ap4 neurons provides a comprehensive view of the genetic flow controlling the generation of highly unique neuronal cell types in the developing nervous system.
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| 36. |
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| 37. |
- Broström, Anders, et al.
(författare)
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Worldwide estimation of restless legs syndrome : a systematic review and meta-analysis of prevalence in the general adult population
- 2023
-
Ingår i: Journal of Sleep Research. - : John Wiley & Sons. - 0962-1105 .- 1365-2869. ; 32:3
-
Forskningsöversikt (refereegranskat)abstract
- This systematic review, meta-analysis and meta-regression assessed the prevalence of restless legs syndrome (RLS) in the general adult population. Studies identified in Scopus, PubMed, Web of Science, and PsycInfo between January 2000 and February 2022 were included if they used a case–control or cross-sectional design and reported data regarding the prevalence of RLS. The protocol was pre-registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022300709). A total of 97 studies including 483,079 participants from 33 different countries met the eligibility criteria. The Newcastle Ottawa Scale was used to evaluate the methodological quality, and the fill-and-trim method was used to correct probable publication bias, while the jack-knife method was performed to assess small study effect. The corrected overall pooled prevalence of RLS was 3% (95% confidence interval [CI] 1.4%–3.8%). The pooled prevalence of RLS syndrome was affected by methodological quality (no data from non-respondents in the included studies), gender (higher among women), study design (lower prevalence in case–control versus cohort and cross-sectional studies). The figures for corrected pooled prevalence among men, women, alcohol consumers and smokers were 2.8% (95% CI 2%–3.7%); 4.7% (95% CI 3.2%–6.3%); 1.4% (95% CI 0%–4.2%); and 2.7% (95% CI 0%–5.3%), respectively. The prevalence among male and female participants was lower in community-based versus non-community-based studies. Moreover, the prevalence was higher in developed versus developing countries and among elders versus adults. In conclusion, RLS is a common disorder in the general adult population, with a higher prevalence in women; however, prevalence data are affected by study design and quality.
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| 38. |
- Crona, Mikael, et al.
(författare)
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A Rare Combination of Ribonucleotide Reductases in the Social Amoeba Dictyostelium discoideum
- 2013
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 288:12, s. 8198-8208
-
Tidskriftsartikel (refereegranskat)abstract
- Ribonucleotide reductases (RNRs) catalyze the only pathway for de novo synthesis of deoxyribonucleotides needed for DNA replication and repair. The vast majority of eukaryotes encodes only a class I RNR, but interestingly some eukaryotes, including the social amoeba Dictyostelium discoideum, encode both a class I and a class II RNR. The amino acid sequence of the D. discoideum class I RNR is similar to other eukaryotic RNRs, whereas that of its class II RNR is most similar to the monomeric class II RNRs found in Lactobacillus spp. and a few other bacteria. Here we report the first study of RNRs in a eukaryotic organism that encodes class I and class II RNRs. Both classes of RNR genes were expressed in D. discoideum cells, although the class I transcripts were more abundant and strongly enriched during mid-development compared with the class II transcript. The quaternary structure, allosteric regulation, and properties of the diiron-oxo/radical cofactor of D. discoideum class I RNR are similar to those of the mammalian RNRs. Inhibition of D. discoideum class I RNR by hydroxyurea resulted in a 90% reduction in spore formation and decreased the germination viability of the surviving spores by 75%. Class II RNR could not compensate for class I inhibition during development, and an excess of vitamin B12 coenzyme, which is essential for class II activity, did not improve spore formation. We suggest that class I is the principal RNR during D. discoideum development and growth and is important for spore formation, possibly by providing dNTPs for mitochondrial replication.
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| 39. |
- Eek, Tom, et al.
(författare)
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Neural suppression in odor recognition memory
- 2023
-
Ingår i: Chemical Senses. - : Oxford University Press. - 0379-864X .- 1464-3553. ; 48
-
Tidskriftsartikel (refereegranskat)abstract
- Little is known about the neural basis of lower- and higher-order olfactory functions such as odor memory, compared with other sensory systems. The aim of this study was to explore neural networks and correlates associated with 3 functions: passive smelling (PS), odor encoding (OE), and in particular odor recognition memory (ORM). Twenty-six healthy participants were examined using functional magnetic resonance imaging conducted across 3 sessions, one for each function. Independent component analysis revealed a difference between sessions where a distinct ORM component incorporating hippocampus and posterior cingulate showed delayed triggering dissociated from odor stimulation and recognition. By contrasting Hit for ORM (target odors correctly recognized as old) and a combination of PS and detected odors from OE, we found significantly lower activations in amygdala, piriform cortex, insula, thalamus, and the inferior parietal lobule. Region of interest analysis including anterior insula, posterior cingulate gyrus, dentate gyrus, left middle frontal gyrus, amygdala, and piriform cortex demonstrated that Hit were associated with lower activations compared with other memory responses. In summary, our findings suggest that successful recognition of familiar odors (odor familiarity) is associated with neural suppression in the abovementioned regions of interest. Additionally, network including the hippocampus and posterior cingulate is engaged in a postrecognition process. This process may be related to incidental encoding of less familiar and more novel odors (odor novelty) and should be subject for future research.
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| 40. |
- Eklöf, Karin, et al.
(författare)
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Trends in mercury, lead and cadmium concentrations in 27 European streams and rivers: 2000–2020
- 2024
-
Ingår i: Environmental Pollution. - Göteborg : IVL Svenska Miljöinstitutet. - 0269-7491 .- 1873-6424. ; 360, s. 124761-124761
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Tidskriftsartikel (refereegranskat)abstract
- Temporal trends for concentrations of mercury (Hg), lead (Pb) and cadmium (Cd) were evaluated from year 2000–2020 in 20 (Hg), 23 (Pb) and 11 (Cd) watercourses in remote forest catchments in Europe. Decreasing trends were observed in 15% (Hg), 39% (Pb) and 45% (Cd) of the watercourses during the period of evaluation. Decreasing trends were mainly observed between 2000 and 2005 for Hg and between 2000 and 2015 for Pb and Cd. For the last five years of the studied time period (2015–2020), more watercourses showed significant increasing, rather than decreasing Hg, Pb and Cd trends.This was interpreted as a legacy effect of metals still retained in catchment soils. The overall negative trends during the earlier part of the study period were likely driven by declining deposition of metals over Europe, especially for Pb and Cd. Other changes related to metal transport and chemistry may have contributed to the observed trends as well, including recovery from acidification and the ongoing browning of surface waters at northern latitudes. Here we found that organic carbon could explain the seasonal variation in Hg and Pb, but was not related the interannual trends. This study highlights the need for long-term monitoring and robust statistical methods that can detect multidirectional, long-term change in water chemistry.
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| 41. |
- Eleftheriou, Andreas, et al.
(författare)
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Circadian rhythm in idiopathic normal pressure hydrocephalus
- 2018
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Ingår i: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print). - : ELSEVIER SCIENCE BV. - 0303-8467 .- 1872-6968. ; 164, s. 72-74
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The pathogenesis of idiopathic normal pressure hydrocephalus (iNPH) takes place in structures close to the cerebral ventricular system. Suprachiasmatic nucleus (SCN), situated close to the third ventricle, is involved in circadian rhythm. Diurnal disturbances are well-known in demented patients. The cognitive decline in iNPH is potentially reversible after a shunt operation. Diurnal rhythm has never been studied in iNPH. We hypothesize that there is a disturbance of circadian rhythm in iNPH-patients and the aim was to study any changes of the diurnal rhythm (mesor and circadian period) as well as any changes of the diurnal amplitude and acrophase of the activity in iNPH-patients before and after a shunt operation. Patients and methods: Twenty consecutive iNPH-patients fulfilling the criteria of the American iNPH-guidelines, 9 males and 11 females, mean age 73 (49-81) years were included. The patients underwent a pre-operative clinical work-up including 10 m walk time (w10mt) steps (w10 ms), TUG-time (TUGt) and steps (TUGs) and for cognitive function an MMSE score was measured. In order to receive circadian rhythm data actigraphic recordings were performed using the SenseWear 2 (BodyMedia Inc Pittsburgh, PA, USA) actigraph. Cosinor analyses of accelerometry data were performed in "R" using non-linear regression with Levenburg-Marquardt estimation. Pre- and post-operative data regarding mesor, amplitude and circadian period were compared using Wilcoxon-Mann-Whitney test for paired data. Results: Twenty patients were evaluated before and three month post-operatively. Motor function (w10mt, w10 ms, TUGt, TUGs) was significantly improved while MMSE was not significantly changed. Actigraphic measurements (mesor, amplitude and circadian period) showed no significant changes after shunt operation. Conclusion: This is the first systematic study of circadian rhythm in iNPH-patients. We found no significant changes in circadian rhythm after shunt surgery. The conceptual idea of diurnal rhythm changes in hydrocephalus is still interesting from a theoretical standpoint and warrants further studies that could include a combination of better designed actigraphic studies in combination with neuroendocrine markers and imaging methods
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| 42. |
- Eleftheriou, Andreas, et al.
(författare)
-
Indication of Thalamo-Cortical Circuit Dysfunction in Idiopathic Normal Pressure Hydrocephalus : A Tensor Imaging Study
- 2020
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Idiopathic normal pressure hydrocephalus (iNPH) is a disorder with unclear pathophysiology. The diagnosis of iNPH is challenging due to its radiological similarity with other neurodegenerative diseases and ischemic subcortical white matter changes. By using Diffusion Tensor Imaging (DTI) we explored differences in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in iNPH patients (before and after a shunt surgery) and healthy individuals (HI) and we correlated the clinical results with DTI parameters. Thirteen consecutive iNPH-patients underwent a pre- and post-operative clinical work-up: 10m walk time (w10mt) steps (w10ms), TUG-time (TUGt) and steps (TUGs); for cognitive function MMSE. Nine HI were included. DTI was performed before and 3 months after surgery, HI underwent DTI once. DTI differences analyzed by manually placing 12 regions-of-interest. In patients motor and balance function improved significantly after surgery (p=0.01, p=0.025). Higher nearly significant FA values found in the patients vs HI pre-operatively in the thalamus (p=0.07) accompanied by an almost significant lower ADC (p=0.08). Significantly FA and ADC-values were found between patients and HI in FWM (p=0.02, p=0.001) and almost significant (p=0.057) pre- vs postoperatively. Postoperatively we found a trend towards the HIs FA values and a strong significant negative correlation between FA changes vs. gait results in the FWM (r=-0.7, p=0.008). Our study gives a clear indication of an ongoing pathological process in the periventricular white matter, especially in the thalamus and in the frontal white matter supporting the hypothesis of a shunt reversible thalamo-cortical circuit dysfunction in iNPH.
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| 43. |
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| 44. |
- Eleftheriou, Andreas, et al.
(författare)
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Optical Coherence Tomography Revealing Ganglion Cell Loss in Idiopathic Normal Pressure Hydrocephalus
- 2021
-
Ingår i: World Neurosurgery. - : Elsevier Science. - 1878-8750 .- 1878-8769. ; 149, s. E1061-E1066
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although there may theoretically be a disturbance in the eye or the visual pathways due to abnormal cerebrospinal fluid (CSF) dynamics in idiopathic normal pressure hydrocephalus (iNPH), it has not been studied systemically. Optical coherence tomography (OCT) is a noninvasive, reproducible procedure for quantitative and qualitative analysis of retinal morphology. METHODS: OCT was used to study the eye fundus before and after a CSF tap test in patients with iNPH compared with healthy individuals (HIs). Twelve patients with iNPH (6 females and 6 males) with a median age of 76 years (64-84 years) and 21 HIs (11 females and 10 males) with a median age of 73 years (64-79 years) were included. The patients underwent neurological, cognitive, and physiotherapeutic evaluation. Brain magnetic resonance imaging, CSF tap test via lumbar puncture, and subsequently CSF analysis were performed. OCT was performed before and after CSF removal. HIs underwent OCT once. RESULTS: The patients had significantly reduced retinal ganglion cell layer thickness 71 mu m (56-81 mu m) compared with the HIs, 79.5 mu m (72-90 mu m) (P = 0.001), but no sig -ificant changes were observed before or after the CSF tap test. All patients improved in motor function in a 10-m walk test after the CSF tap test. The median CSF pressure was 15 and 1 cm H2O, respectively, before and after lumbar puncture with removal of median 43.5 mL CSF. CONCLUSIONS: This pilot study shows OCT findings that differ from HIs and implies a rational for becoming a valuable tool in the diagnosis of iNPH. Further studies are warranted to elucidate the pathology of the retina in iNPH.
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| 45. |
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| 46. |
- Eleftheriou, Andreas, et al.
(författare)
-
Tick-borne Encephalitis: Stroke-like Presentation
- 2019
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Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : ELSEVIER. - 1052-3057 .- 1532-8511. ; 28:8, s. E119-E122
-
Tidskriftsartikel (refereegranskat)abstract
- Tick-borne encephalitis, caused by the tick-borne virus (TBEV), is endemic in central, eastern, and northern Europe eastwards through Russian Siberia and China. For the year 2009, the highest incidence in Scandinavian countries was in Sweden. The clinical symptoms have a wide spectrum. We report a unique case of clinical symptoms and radiological findings compatible with a stroke-like inflammatory lesion in the thalamus, suggesting microangiopathy from TBEV. Our case shows that TBEV could be a possible cause of stroke-like lesions.
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| 47. |
- Eriksson Domellöf, Magdalena, et al.
(författare)
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Olfactory dysfunction and dementia in newly diagnosed patients with Parkinson's disease
- 2017
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 38, s. 41-47
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Studies report that up to 90% of patients with idiopathic Parkinson's disease (PD) have olfactory dysfunction (hyposmia). Hyposmia has also been connected to cognitive impairment and dementia in PD, but no studies of newly diagnosed patients followed longer than three years exists. The present study investigates the prevalence of olfactory dysfunction at PD diagnosis, how it evolves over time and whether hyposmia increases the risk of dementia in Parkinson's disease.METHODS: Olfactory function was assessed with Brief Smell Identification Test (B-SIT) in 125 newly diagnosed patients with PD. They were followed for a maximum of 10 years (median six years) with extensive investigations at baseline, 12, 36, 60 and 96 months. Patients with B-SIT<9 were considered hyposmic.RESULTS: Hyposmia was found in 73% of the patients at diagnosis. During the follow up period of ten years 42 (46%) patients with hyposmia at baseline developed dementia compared to seven (21%) of the normosmic patients. Cox proportional hazards model showed that hyposmia at baseline (controlled for age, gender, UPDRS III and Mild Cognitive Impairment) increased the risk of developing dementia (hazard ratio (95%CI): 3.29 (1.44-7.52), p = 0.005). Only one of 22 patients with normal cognition and normal olfaction at baseline developed dementia.CONCLUSIONS: Olfactory dysfunction was common at the time of PD diagnosis and increased the risk of dementia up to ten years after PD diagnosis regardless of baseline cognitive function. Normal olfaction together with normal cognition at baseline predicted a benign cognitive course up to ten years after diagnosis.
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| 48. |
- Evestedt, Fredrik, et al.
(författare)
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Altering Flux Density Harmonics in the Air-gap of Synchronous Machines by Active Control of the Field Current
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Ingår i: IEEE Transactions on Industrial Electronics. - 0278-0046 .- 1557-9948.
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Tidskriftsartikel (refereegranskat)abstract
- Flux density harmonics in the air-gap of electrical machines create distorted voltage waveforms and can induce vibrations. These problems are difficult to mitigate when the machine is already in operation and therefore a lot of effort is made during the design phase to eliminate them. Still, many in-operation machines experience problems related to harmonics and often the solution is to mechanically reinforce and change modal shapes which is expensive and inconvenient. Using a current controlled switched power supply to excite a synchronous machine and adding specific harmonics to the DC-field current it is shown that it is possible to alter the harmonic content of the flux density in the air-gap, and thus affect voltage harmonics and the exciting magnetic forces. The method is verified and compared with simulations and experiments on an existing electrical machine.
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| 49. |
- Evestedt, Fredrik, et al.
(författare)
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Controlling airgap magnetic flux density harmonics in synchronous machines using field current injection
- 2021
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Ingår i: Electrical engineering (Berlin. Print). - : Springer. - 0948-7921 .- 1432-0487. ; 103, s. 195-203
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, a method to control the harmonic content of the magnetic flux density in the airgap of a synchronous machine is presented. Voltage harmonics in one phase as well as the exciting magnetic forces can be affected. Switched power electronics were used to provide the field current to a synchronous machine, the control added specific current harmonics to the DC field current in order to minimize either voltage harmonics or magnetic forces. The method is verified and compared with simulations and experiments on an existing electrical machine.
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| 50. |
- Evestedt, Fredrik
(författare)
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Improving the functionality of synchronous machines using power electronics
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- With the advent of modern power electronics there is reason to explore what can be achieved when it is applied to a mature technology like synchronous machines. In this text several concepts will be presented on how it is possible to control forces and how to get better performance out of synchronous machines by using power electronics. Methodologies to create radial forces by controlling the field current in a standard series connected rotor winding as well as when the winding is split in to several segments is presented. By segmenting the rotor a resulting force vector can be created to cancel forces due to unbalanced magnetic pull.It is also shown that inverting the field current with respect to the stator field enables line start of synchronous machines without using damper bars, frequency converters, or starting motors.Some first results from the installation and testing of an electromagnetic thrust bearing installed in unit U9 in the hydropower station in Porjus are presented. The benefits of the system is increased reliability and higher efficiency of the thrust bearing system.An evaluation of a 2-stage brushless excitation system was done, different rotating power electronics topologies were tested in the stationary frame connected to a six-phase permanent magnet brushless exciter. The rotating control and measurement system for the power electronics is presented. Potential benefits of the system is that there is no need for brushes to transfer the field current to the rotor winding, fast response time due to actively controlled electronics, independence of the station bus voltage, and reduced maintenance.
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