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  • Labit, B., et al. (författare)
  • Dependence on plasma shape and plasma fueling for small edge-localized mode regimes in TCV and ASDEX Upgrade
  • 2019
  • Ingår i: Nuclear Fusion. - : Institute of Physics Publishing (IOPP). - 0029-5515 .- 1741-4326. ; 59:8
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2019 Institute of Physics Publishing. All rights reserved. Within the EUROfusion MST1 work package, a series of experiments has been conducted on AUG and TCV devices to disentangle the role of plasma fueling and plasma shape for the onset of small ELM regimes. On both devices, small ELM regimes with high confinement are achieved if and only if two conditions are fulfilled at the same time. Firstly, the plasma density at the separatrix must be large enough (ne,sep/nG ∼ 0.3), leading to a pressure profile flattening at the separatrix, which stabilizes type-I ELMs. Secondly, the magnetic configuration has to be close to a double null (DN), leading to a reduction of the magnetic shear in the extreme vicinity of the separatrix. As a consequence, its stabilizing effect on ballooning modes is weakened.
  • Meyer, H.F., et al. (författare)
  • Overview of physics studies on ASDEX Upgrade
  • 2019
  • Ingår i: Nuclear Fusion. - : IOP PUBLISHING LTD. - 0029-5515 .- 1741-4326. ; 59:11
  • Forskningsöversikt (refereegranskat)abstract
    • The ASDEX Upgrade (AUG) programme, jointly run with the EUROfusion MST1 task force, continues to significantly enhance the physics base of ITER and DEMO. Here, the full tungsten wall is a key asset for extrapolating to future devices. The high overall heating power, flexible heating mix and comprehensive diagnostic set allows studies ranging from mimicking the scrape-off-layer and divertor conditions of ITER and DEMO at high density to fully non-inductive operation (q 95 = 5.5, ) at low density. Higher installed electron cyclotron resonance heating power 6 MW, new diagnostics and improved analysis techniques have further enhanced the capabilities of AUG. Stable high-density H-modes with MW m-1 with fully detached strike-points have been demonstrated. The ballooning instability close to the separatrix has been identified as a potential cause leading to the H-mode density limit and is also found to play an important role for the access to small edge-localized modes (ELMs). Density limit disruptions have been successfully avoided using a path-oriented approach to disruption handling and progress has been made in understanding the dissipation and avoidance of runaway electron beams. ELM suppression with resonant magnetic perturbations is now routinely achieved reaching transiently . This gives new insight into the field penetration physics, in particular with respect to plasma flows. Modelling agrees well with plasma response measurements and a helically localised ballooning structure observed prior to the ELM is evidence for the changed edge stability due to the magnetic perturbations. The impact of 3D perturbations on heat load patterns and fast-ion losses have been further elaborated. Progress has also been made in understanding the ELM cycle itself. Here, new fast measurements of and E r allow for inter ELM transport analysis confirming that E r is dominated by the diamagnetic term even for fast timescales. New analysis techniques allow detailed comparison of the ELM crash and are in good agreement with nonlinear MHD modelling. The observation of accelerated ions during the ELM crash can be seen as evidence for the reconnection during the ELM. As type-I ELMs (even mitigated) are likely not a viable operational regime in DEMO studies of 'natural' no ELM regimes have been extended. Stable I-modes up to have been characterised using -feedback. Core physics has been advanced by more detailed characterisation of the turbulence with new measurements such as the eddy tilt angle - measured for the first time - or the cross-phase angle of and fluctuations. These new data put strong constraints on gyro-kinetic turbulence modelling. In addition, carefully executed studies in different main species (H, D and He) and with different heating mixes highlight the importance of the collisional energy exchange for interpreting energy confinement. A new regime with a hollow profile now gives access to regimes mimicking aspects of burning plasma conditions and lead to nonlinear interactions of energetic particle modes despite the sub-Alfvénic beam energy. This will help to validate the fast-ion codes for predicting ITER and DEMO.
  • Ahmed, N., et al. (författare)
  • Consensus statements and recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 11-13 November 2018
  • 2019
  • Ingår i: European Stroke Journal. - 2396-9873 .- 2396-9881. ; 4:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of the European Stroke Organisation-Karolinska Stroke Update Conference is to provide updates on recent stroke therapy research and to give an opportunity for the participants to discuss how these results may be implemented into clinical routine. The meeting started 22 years ago as Karolinska Stroke Update, but since 2014 it is a joint conference with European Stroke Organisation. Importantly, it provides a platform for discussion on the European Stroke Organisation guidelines process and on recommendations to the European Stroke Organisation guidelines committee on specific topics. By this, it adds a direct influence from stroke professionals otherwise not involved in committees and work groups on the guideline procedure. The discussions at the conference may also inspire new guidelines when motivated. The topics raised at the meeting are selected by the scientific programme committee mainly based on recent important scientific publications. This year's European Stroke Organisation-Karolinska Stroke Update Meeting was held in Stockholm on 11-13 November 2018. There were 11 scientific sessions discussed in the meeting including two short sessions. Each session except the short sessions produced a consensus statement (Full version with background, issues, conclusions and references are published as web-material and at and ) and recommendations which were prepared by a writing committee consisting of session chair(s), scientific secretary and speakers. These statements were presented to the 250 participants of the meeting. In the open meeting, general participants commented on the consensus statement and recommendations and the final document were adjusted based on the discussion from the general participants Recommendations (grade of evidence) were graded according to the 1998 Karolinska Stroke Update meeting with regard to the strength of evidence. Grade A Evidence: Strong support from randomised controlled trials and statistical reviews (at least one randomised controlled trial plus one statistical review). Grade B Evidence: Support from randomised controlled trials and statistical reviews (one randomised controlled trial or one statistical review). Grade C Evidence: No reasonable support from randomised controlled trials, recommendations based on small randomised and/or non-randomised controlled trials evidence.
  • He, W., et al. (författare)
  • CYP2D6 genotype predicts tamoxifen discontinuation and drug response : a secondary analysis of the KARISMA trial
  • 2021
  • Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534. ; 32:10, s. 1286-1293
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Guidelines regarding whether tamoxifen should be prescribed based on women's cytochrome P450 2D6 (CYP2D6) genotypes are conflicting and have caused confusion. This study aims to investigate if CYP2D6 metabolizer status isa associated with tamoxifen-related endocrine symptoms, tamoxifen discontinuation, and mammographic density change. Patients and methods: We used data from 1440 healthy women who participated the KARISMA dose determination trial. Endocrine symptoms were measured using a modified Functional Assessment of Cancer Therapy – Endocrine Symptoms (FACT-ES) questionnaire. Change in mammographic density was measured and used as a proxy for tamoxifen response. Participants were genotyped and categorized as poor, intermediate, normal, or ultrarapid CYP2D6 metabolizers. Results: The median endoxifen level per mg oral tamoxifen among poor, intermediate, normal and ultrarapid CYP2D6 metabolizers were 0.18 ng/ml, 0.38 ng/ml, 0.56 ng/ml and 0.67 ng/ml, respectively. Ultrarapid CYP2D6 metabolizers were more likely than other groups to report a clinically relevant change in cold sweats, hot flash, mood swings, being irritable, as well as the overall modified FACT-ES score, after taking tamoxifen. The 6-month tamoxifen discontinuation rates among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were 25.7%, 23.6%, 28.6%, and 44.4%, respectively. Among those who continued and finished the 6-month tamoxifen intervention, the mean change in dense area among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were −0.8 cm2, −4.5 cm2, −4.1 cm2, and −8.0 cm2 respectively. Conclusions: Poor CYP2D6 metabolizers are likely to experience an impaired response to tamoxifen, measured through mammographic density reduction. In contrast, ultrarapid CYP2D6 metabolizers are at risk for exaggerated response with pronounced adverse effects that may lead to treatment discontinuation.
  • Benrick, Anna, 1979, et al. (författare)
  • Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture
  • 2017
  • Ingår i: Faseb Journal. - : Federation of American Societies for Experimental Biology. - 0892-6638 .- 1530-6860. ; 31:8, s. 3288-3297
  • Tidskriftsartikel (refereegranskat)abstract
    • A single bout of low-frequency electroacupuncture (EA) causing muscle contractions increases whole-body glucose uptake in insulin-resistant rats. We explored the underlying mechanism of this finding and whether it can be translated into clinical settings. Changes in glucose infusion rate (GIR) were measured by euglycemic-hyperinsulinemic clamp during and after 45 min of low-frequency EA in 21 overweight/obese women with polycystic ovary syndrome (PCOS) and 21 controls matched for age, weight, and body mass index (experiment 1) and in rats receiving autonomic receptor blockers (experiment 2). GIR was higher after EA in controls and women with PCOS. Plasma serotonin levels and homovanillic acid, markers of vagal activity, decreased in both controls and patients with PCOS. Adipose tissue expression of pro-nerve growth factor (proNGF) decreased, and the mature NGF/proNGF ratio increased after EA in PCOS, but not in controls, suggesting increased sympathetic-driven adipose tissue metabolism. Administration of alpha-/beta-adrenergic receptor blockers in rats blocked the increase in GIR in response to EA. Muscarinic and dopamine receptor antagonist also blocked the response but with slower onset. In conclusion, a single bout of EA increases whole-body glucose uptake by activation of the sympathetic and partly the parasympathetic nervous systems, which could have important clinical implications for the treatment of insulin resistance.
  • Eriksson, Mikael, et al. (författare)
  • Low-Dose Tamoxifen for Mammographic Density Reduction : A Randomized Controlled Trial
  • 2021
  • Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X. ; 39:17, s. 1899-1908
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Tamoxifen prevents breast cancer in high-risk women and reduces mortality in the adjuvant setting. Mammographic density change is a proxy for tamoxifen therapy response. We tested whether lower doses of tamoxifen were noninferior to reduce mammographic density and associated with fewer symptoms.PATIENTS AND METHODS: Women, 40-74 years of age, participating in the Swedish mammography screening program were invited to the 6-month double-blind six-arm randomized placebo-controlled noninferiority dose-determination KARISMA phase II trial stratified by menopausal status (EudraCT 2016-000882-22). In all, 1,439 women were accrued with 1,230 participants accessible for intention-to-treat analysis. The primary outcome was proportion of women treated with placebo, 1, 2.5, 5, and 10 mg whose mammographic density decreased at least as much as the median reduction in the 20 mg arm. The noninferior margin was 17%. Secondary outcome was reduction of symptoms. Post hoc analyses were performed by menopausal status. Per-protocol population and full population were analyzed in sensitivity analysis.RESULTS: The 1,439 participants, 566 and 873 pre- and postmenopausal women, respectively, were recruited between October 1, 2016, and September 30, 2019. The participants had noninferior mammographic density reduction following 2.5, 5, and 10 mg tamoxifen compared with the median 10.1% decrease observed in the 20 mg group, a reduction confined to premenopausal women. Severe vasomotor symptoms (hot flashes, cold sweats, and night sweats) were reduced by approximately 50% in the 2.5, 5, and 10 mg groups compared with the 20 mg group.CONCLUSION: Premenopausal women showed noninferior magnitude of breast density decrease at 2.5 mg of tamoxifen, but fewer side effects compared with the standard dose of 20 mg. Future studies should test whether 2.5 mg of tamoxifen reduces the risk of primary breast cancer.
  • Sjöblom, K, et al. (författare)
  • Patient evaluation of a new injection pen for growth hormone treatment in children and adults.
  • 1995
  • Ingår i: Acta paediatrica (Oslo, Norway : 1992). Supplement. - 0803-5326. ; 411, s. 63-5
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to evaluate patients' perception and acceptance of a new multi-dose injection device (Genotropin Pen) for recombinant growth hormone (GH) supplied in a two-chamber cartridge. The pen is combined with a very thin needle (B-D Microfine + (29 G) and meets future demands when dosing of GH will be changed from International Units (IU) to milligrams (mg). A total of 39 children receiving GH treatment (East Hospital, Gothenburg and St Bartholomew's Hospital, London), aged between 7 and 17 years, and 39 GH-treated adults (Sahlgrenska Hospital, Gothenburg and Karolinska Hospital, Stockholm), aged between 20 and 68 years, participated in the study. The daily dose ranged from 0.3 mg to 2.6 mg. The injections were given subcutaneously, once daily, and most of the patients used the thigh as an injection site. After a trial period of 2 weeks, injection technique, pain, fear of injection and convenience of the Genotropin Pen were compared with the experience with the prestudy device (Genotropin KabiPen 16, 16(8) or 36) by questionnaire. A total of 95% of the patients preferred the Genotropin Pen to the prestudy device for the following reasons: a greater certainty of correct dosing with the digital display; the possibility of correcting the set dose; the lock function of the injection button when injection is complete; more comfortable to hold due to the design and the plastic material; and reduced pain when injecting due to the thinner needles. Four patients (5%) preferred the prestudy device KabiPen as they considered this to be 'good enough'. Thus, the Genotropin Pen is a convenient injection device and most patients prefer it to the KabiPen.
  • Skrifvars, M. B., et al. (författare)
  • Do patient characteristics or factors at resuscitation influence long-term outcome in patients surviving to be discharged following in-hospital cardiac arrest?
  • 2007
  • Ingår i: J Intern Med. - : Wiley-Blackwell Publishing Ltd.. - 0954-6820 .- 1365-2796. ; 262:4, s. 488-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction. Few studies have focused on factors influencing long-term outcome following in-hospital cardiac arrest. The present study assesses whether long-term outcome is influenced by difference in patient factors or factors at resuscitation. Methods. An analysis of cardiac arrest data collected from one Swedish tertiary hospital and from five Finnish secondary hospitals supplemented with data on 1 year survival. Multiple logistic regression analysis was used to identify factors associated with survival at 12 months. Results. A total of 441 patients survived to hospital discharge following in-hospital cardiac arrest and 359 (80%) were alive at 12 months. Factors independently associated with survival [odds ratio (OR) >1 indicates increased survival and <1 decreased survival] at 12 months were; age [OR 0.95, 95% confidence interval (CI) 0.93-0.98], renal disease (OR 0.3, CI 0.1-0.9), good functional status at discharge (OR 4.9, CI 1.3-18.9), arrest occurring at (compared with arrests on general wards) emergency wards (OR 4.7, CI 1.4-15.3), cardiac care unit (OR 2.8, CI 1.2-6.4), intensive care unit (OR 2.4, CI 1.1-5.7), ward for thoracic surgery (OR 10.2, CI 2.6-40.1) and unit for interventional radiology (OR 13.3, CI 3.4-52.0). There was no difference in initial rhythm, delay to defibrillation or delay to return of spontaneous circulation between survivors and nonsurvivors. Conclusion. Several patient factors, mainly age, functional status and co-morbid disease, influence long-term survival following cardiac arrest in hospital. The location where the arrest occurred also influences survival, but initial rhythm, delay to defibrillation and to return of spontaneous circulation do not.
  • Holmer, Helene, et al. (författare)
  • Fracture incidence in GH-deficient patients on complete hormone replacement including GH
  • 2007
  • Ingår i: Journal of Bone and Mineral Research. - : AMBMR. - 1523-4681 .- 0884-0431. ; 22:12, s. 1842-1850
  • Tidskriftsartikel (refereegranskat)abstract
    • Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men. Introduction: The objective of this study was to evaluate fracture incidence in patients with confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential Confounders and effect modifiers into account. Materials and Methods: Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively. Results: A more than doubled risk (IRR, 2.29; 95 % CI 1.23-4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR, 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% C1, 0.34-0.86) was recorded in AO GHD men. Conclusions: Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH-IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.
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