| 1. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 2. |
- Berglund, Johan, et al.
(författare)
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Prospective motion correction for diffusion weighted EPI of the brain using an optical markerless tracker.
- 2021
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 85:3, s. 1427-1440
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To enable motion-robust diffusion weighted imaging of the brain using well-established imaging techniques.METHODS: An optical markerless tracking system was used to estimate and correct for rigid body motion of the head in real time during scanning. The imaging coordinate system was updated before each excitation pulse in a single-shot EPI sequence accelerated by GRAPPA with motion-robust calibration. Full Fourier imaging was used to reduce effects of motion during diffusion encoding. Subjects were imaged while performing prescribed motion patterns, each repeated with prospective motion correction on and off.RESULTS: Prospective motion correction with dynamic ghost correction enabled high quality DWI in the presence of fast and continuous motion within a 10° range. Images acquired without motion were not degraded by the prospective correction. Calculated diffusion tensors tolerated the motion well, but ADC values were slightly increased.CONCLUSIONS: Prospective correction by markerless optical tracking minimizes patient interaction and appears to be well suited for EPI-based DWI of patient groups unable to remain still including those who are not compliant with markers.
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| 3. |
- Agewall, Stefan, et al.
(författare)
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Efterlyses : politik mot hjärtinfarkt
- 2013
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Ingår i: Läkartidningen. - Stockholm : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 110:13-14, s. 664-
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Anand, Sonia S, et al.
(författare)
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Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial.
- 2018
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Ingår i: Lancet (London, England). - 1474-547X. ; 391:10117, s. 219-229
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Tidskriftsartikel (refereegranskat)abstract
- Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.Bayer AG.
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| 5. |
- Anell, Anders, et al.
(författare)
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A randomized comparison between league tables and funnel plots as an aid to health care decision-making
- 2017
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Ingår i: International Journal for Quality in Health Care. - : Oxford University Press (OUP). - 1464-3677 .- 1353-4505. ; 28:6, s. 816-823
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Tidskriftsartikel (refereegranskat)abstract
- Objective Comparison of provider performance is commonly used to inform health care decision-making. Little attention has been paid to how data presentations influence decisions. This study analyzes differences in suggested actions by decision-makers informed by league tables or funnel plots.Design Decision-makers were invited to a survey and randomized to compare hospital performance using either league tables or funnel plots for four different measures within the area of cancer care. For each measure, decision-makers were asked to suggest actions towards 12–16 hospitals (no action, ask for more information, intervene) and provide feedback related to whether the information provided had been useful.Setting Swedish health care.Participants Two hundred and twenty-one decision-makers at administrative and clinical levels.Intervention Data presentations in the form of league tables or funnel plots.Main outcome measures Number of actions suggested by participants. Proportion of appropriate actions.Results For all four measures, decision-makers tended to suggest more actions based on the information provided in league tables compared to funnel plots (44% vs. 21%, P < 0.001). Actions were on average more appropriate for funnel plots. However, when using funnel plots, decision-makers more often missed to react even when appropriate.Conclusions The form of data presentation had an influence on decision-making. With league tables, decision-makers tended to suggest more actions compared to funnel plots. A difference in sensitivity and specificity conditioned by the form of presentation could also be identified, with different implications depending on the purpose of comparisons. Explanations and visualization aids are needed to support appropriate actions.
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| 6. |
- Anselm, Jonas, et al.
(författare)
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Bannlys alla politiska beslut som ger mer klimatutsläpp
- 2014
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Ingår i: Dagens Nyheter.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Torftig valdebatt. Dagspolitiken klarar inte att hantera ödesfrågan om klimatet, vilket oroar oss. Vi föreslår därför ett ”utsläppsmoratorium”: inga beslut får tas som ökar utsläppen av växthusgaser. Principen måste kopplas till mål om exempelvis förnybar energi och grön infrastruktur, skriver 23 forskare och debattörer.
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| 7. |
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| 8. |
- Avventi, Enrico, et al.
(författare)
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Projection-based 3D/2D registration for prospective motion correction.
- 2020
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 84:3, s. 1534-1542
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To develop a registration method that is capable of estimating the full range of rigid body motion from three orthogonal collapsed images of the head. These images can be obtained using the collapsed FatNav, a previously introduced navigator for prospective motion correction. It combines a short duration with wide compatibility with different main sequences due to its robustness against spin history effects.THEORY AND METHODS: A projection-based 3D/2D registration method is presented and then modified to take into account the peculiarities of the collapsed FatNav. Water/fat separated volumes were used in simulations to assess the accuracy of the proposed method at different resolutions by comparison with high-resolution 3D registration. The sensitivity with respect to masking strategies and starting motion parameters was investigated. Finally, prospective experiments with a healthy volunteer were performed with different types of motion patterns. A PROPELLER main sequence was chosen to compare the prospective correction with PROPELLER's own retrospective correction.RESULTS: In the simulations the proposed method has shown comparable performance to 3D registration. Furthermore, evidence of its robustness with respect to masking strategies and starting motion parameters was presented. The combination with collapsed FatNav has performed well in correcting most of the motion artifacts prospectively with improved image quality compared to only using PROPELLER's retrospective motion correction.CONCLUSIONS: The proposed 3D/2D registration together with collapsed FatNav is characterized by a good balance between navigator duration and estimate accuracy. Further work is needed to validate the method across a wider variety of subject anatomies.
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| 9. |
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| 10. |
- Berglund, Johan, et al.
(författare)
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Fat/water separation in k-space with real-valued estimates and its combination with POCS.
- 2020
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 83:2, s. 653-661
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To develop reconstruction methods for improved image quality of chemical shift displacement-corrected fat/water imaging combined with partial Fourier acquisition.THEORY: Fat/water separation in k-space enables correction of chemical shift displacement. Modeling fat and water as real-valued rather than complex improves the conditionality of the inverse problem. This advantage becomes essential for k-space separation. In this work, it was described how to perform regularized fat/water imaging with real estimates in k-space, and how fat/water imaging can be combined with partial Fourier reconstruction using Projection Onto Convex Sets (POCS).METHODS: The reconstruction methods were demonstrated on chemical shift encoded gradient echo and fast spin echo data from volunteers, acquired at 1.5 T and 3 T. Both fully sampled and partial Fourier acquisitions were made. Data was retrospectively rejected from the fully sampled dataset to evaluate POCS and homodyne reconstruction.RESULTS: Fat/water separation in k-space eliminated chemical shift displacement, while real-valued estimates considerably reduced the noise amplification compared to complex estimates. POCS reconstruction could recover high spatial frequency information in the fat and water images with lower reconstruction error than homodyne. Partial Fourier in the readout direction enabled more flexible choice of gradient echo imaging parameters, in particular image resolution.CONCLUSION: Chemical shift displacement-corrected fat/water imaging can be performed with regularization and real-valued estimates to improve image quality by reducing ill-conditioning of the inverse problem in k-space. Fat/water imaging can be combined with POCS, which offers improved image quality over homodyne reconstruction.
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| 11. |
- Berglund, Johan, et al.
(författare)
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Motion-insensitive susceptibility weighted imaging.
- 2021
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 86:4, s. 1970-1982
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To enable SWI that is robust to severe head movement.METHODS: Prospective motion correction using a markerless optical tracker was applied to all pulse sequences. Three-dimensional gradient-echo and 3D EPI were used as reference sequences, but were expected to be sensitive to motion-induced B0 changes, as the long TE required for SWI allows phase discrepancies to accumulate between shots. Therefore, 2D interleaved snapshot EPI was investigated for motion-robust SWI and compared with conventional 2D EPI. Repeated signal averages were retrospectively corrected for motion. The sequences were evaluated at 3 T through controlled motion experiments involving two cooperative volunteers and SWI of a tumor patient.RESULTS: The performed continuous head motion was in the range of 5-8° rotations. The image quality of the 3D sequences and conventional 2D EPI was poor unless the rotational motion axis was parallel to B0 . Interleaved snapshot EPI had minimal intraslice phase discrepancies due to its small temporal footprint. Phase inconsistency between signal averages was well tolerated due to the high-pass filter effect of the SWI processing. Interleaved snapshot EPI with prospective and retrospective motion correction demonstrated similar image quality, regardless of whether motion was present. Lesion depiction was equal to 3D EPI with matching resolution.CONCLUSION: Susceptibility-based imaging can be severely corrupted by head movement despite accurate prospective motion correction. Interleaved snapshot EPI is a superior alternative for patients who are prone to move and offers SWI which is insensitive to motion when combined with prospective and retrospective motion correction.
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| 12. |
- Borg, Sixten, et al.
(författare)
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Cost-Effectiveness and Heterogeneity: Using Finite Mixtures of Disease Activity Models to Identify and Analyze Phenotypes
- 2015
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Heterogeneity in patient populations is an important issue in health economic evaluations, as the cost-effectiveness of an intervention can vary between patient subgroups, and an intervention which is not cost-effective in the overall population may be cost-effective in particular subgroups. Identifying such subgroups is of interest in the allocation of healthcare resources. Our aim was to develop a method for cost-effectiveness analysis in heterogeneous chronic diseases, by identifying subgroups (phenotypes) directly relevant to the cost-effectiveness of an intervention, and by enabling cost-effectiveness analyses of the intervention in each of these phenotypes. We identified phenotypes based on healthcare resource utilization, using finite mixtures of underlying disease activity models: first, an explicit disease activity model, and secondly, a model of aggregated disease activity. They differed with regards to time-dependence, level of detail, and what interventions they could evaluate. We used them for cost-effectiveness analyses of two hypothetical interventions. Allowing for different phenotypes improved model fit, and was a key step towards dealing with heterogeneity. The cost-effectiveness of the interventions varied substantially between phenotypes. Using underlying disease activity models for identifying phenotypes as well as cost-effectiveness analysis appears both feasible and useful in that they guide the decision to introduce an intervention.
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| 13. |
- Borg, Åke, et al.
(författare)
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ERBB2 amplification is associated with tamoxifen resistance in steroid-receptor positive breast cancer
- 1994
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Ingår i: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 81:2, s. 137-144
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Tidskriftsartikel (refereegranskat)abstract
- Amplification and overexpression of the ERBB2 (HER-2/neu) oncogene has been implicated as contributing to the development of human breast cancer, and as a predictor of poor survival. In the present non-randomized study of 871 primary invasive breast tumours, ERBB2 activation was significantly correlated to a shorter disease-free and overall survival in the subgroup of patients receiving adjuvant tamoxifen therapy, but not in the untreated group. Further subcategorization demonstrated the relationship to poor prognosis to be confined to lymph node positive and steroid receptor-positive tumours. We suggest that steroid receptor and ERBB2-positive breast tumours are resistant to tamoxifen therapy and, supported by experimental evidence showing an oestrogen receptor dependent up-regulation of ERBB2 expression upon tamoxifen administration, possibly even growth stimulated by the drug.
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| 14. |
- Chaudhry, Nadia, et al.
(författare)
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Breast Cancer Diagnosis Using Extended-Wavelength–Diffuse Reflectance Spectroscopy (EW-DRS) : Proof of Concept in Ex Vivo Breast Specimens Using Machine Learning
- 2023
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Ingår i: Diagnostics. - 2075-4418. ; 13:19, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- This study aims to investigate the feasibility of using diffuse reflectance spectroscopy (DRS) to distinguish malignant breast tissue from adjacent healthy tissue, and to evaluate if an extended-wavelength range (450–1550 nm) has an advantage over the standard wavelength range (450–900 nm). Multivariate statistics and machine learning algorithms, either linear discriminant analysis (LDA) or support vector machine (SVM) are used to distinguish the two tissue types in breast specimens (total or partial mastectomy) from 23 female patients with primary breast cancer. EW-DRS has a sensitivity of 94% and specificity of 91% as compared to a sensitivity of 40% and specificity of 71% using the standard wavelength range. The results suggest that DRS can discriminate between malignant and healthy breast tissue, with improved outcomes using an extended wavelength. It is also possible to construct a simple analytical model to improve the diagnostic performance of the DRS technique.
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| 15. |
- Ewers, Sven-Börje, et al.
(författare)
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Flow cytometry DNA analysis and prediction of loco-regional recurrences after mastectomy in breast cancer
- 1992
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 31:7, s. 733-740
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Tidskriftsartikel (refereegranskat)abstract
- The study concerns whether DNA flow cytometry and estrogen receptor analysis might help predict which breast cancer patients, particularly node-positive ones, were at the greatest risk of developing loco-regional recurrence (LRR). Such patients would best benefit from postoperative radiotherapy following modified radical mastectomy and axillary lymph node dissection. After this type of surgery, 506 patients were followed up for a median time of nearly 5 years. Among the 235 patients given postoperative radiotherapy, the loco-regional control rate was 100% in N0 cases (n = 93), 94% in cases with 1-3 positive nodes (n = 90), 93% in cases with 4-9 positive nodes (n = 43), and 67% in cases with 10 or more positive nodes (n = 9). Among the 271 non-irradiated patients, the corresponding figures for loco-regional control were 91% in N0 cases (n = 141), 71% in cases with 1-3 positive nodes (n = 84), 65% in cases with 4-9 positive nodes (n = 31), and 67% in cases with 10 or more positive nodes (n = 15). Ploidy status, level of S-phase fraction, estrogen receptor content, and primary tumor size did not, in the present material, yield significant additional information with regard to the risk of LRR in the different nodal subgroups, a finding confirmed in multivariate analysis where the only significant predictor of LRR was the number of positive nodes (p = 0.01). Adjuvant tamoxifen treatment could not replace postoperative radiotherapy for achieving loco-regional tumor control, the overall rate of which was 81% among patients treated with tamoxifen only (n = 117), as compared with 98% among those also treated with radiotherapy (n = 54) (p = 0.003).
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| 16. |
- Fernö, Mårten, et al.
(författare)
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Recurrence-free survival in breast cancer improved by adjuvant tamoxifen--especially for progesterone receptor positive tumors with a high proliferation
- 1995
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217. ; 36:1, s. 23-34
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Tidskriftsartikel (refereegranskat)abstract
- Although the beneficial effect on breast cancer of adjuvant tamoxifen (TAM) is well established, in the series studied by our group this effect seems to have been restricted to patients with steroid receptor (especially progesterone receptor (PgR)) positive tumors. However, as some patients with PgR-positive tumors manifested recurrence despite adjuvant TAM treatment, the question arose whether some other biological factor(s) could be used to identify these non-responding cases. The level of the S-phase fraction (SPF), as measured by flow cytometry, has been shown to be a useful prognostic marker, prognosis being better in cases where the SPF is low than in those where it is high. The aim of the present study was to relate the prognosis after adjuvant TAM to SPF among patients with PgR-positive tumors. In the PgR-positive group as a whole, the effect of TAM on prognosis was more pronounced in the high SPF group than in the low SPF group (p = 0.005) the respective decrease in 3 year recurrence rate was from 19 to 43% and from 17 to 9%. Multivariate analysis of the data for the TAM-treated group showed the level of PgR concentration (low positive vs. high positive), lymph node status, and tumor size to be independent predictive factors, but not the level of SPF (i.e. high vs. low). By contrast, among patients not treated with TAM, the SPF was a strong independent prognostic factor. To sum up, SPF was a strong independent predictor of outcome only for patients receiving no systemic adjuvant therapy, but not in patients receiving adjuvant TAM. Patients with PgR-positive and high S-phase tumors derived more benefit from TAM than patients with PgR-positive and low SPF tumors.
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| 17. |
- Flanagan, John N., et al.
(författare)
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Role of follistatin in promoting adipogenesis in women
- 2009
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 94:8, s. 3003-9
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Follistatin is a glycoprotein that binds and neutralizes biological activities of TGFbeta superfamily members including activin and myostatin. We previously identified by expression profiling that follistatin levels in white adipose tissue (WAT) were regulated by obesity. OBJECTIVE: The objective of the study was to elucidate the role of follistatin in human WAT and obesity. DESIGN: We measured secreted follistatin protein from WAT biopsies and fat cells in vitro. We also quantified follistatin mRNA expression in sc and visceral WAT and in WAT-fractionated cells and related it to obesity status, body region, and cellular origin. We investigated the effects of follistatin on adipocyte differentiation of progenitor cells in vitro. PARTICIPANTS: Women (n = 66) with a wide variation in body mass index were recruited by advertisement and from a clinic for weight-reduction therapy. RESULTS: WAT secreted follistatin in vitro. Follistatin mRNA levels in sc but not visceral WAT were decreased in obesity and restored to nonobese levels after weight reduction. Follistatin mRNA levels were high in the stroma-vascular fraction of WAT and low in adipocytes. Recombinant follistatin treatment promoted adipogenic differentiation of progenitor cells and neutralized the inhibitory action of myostatin on differentiation in vitro. Moreover, activin and myostatin signaling receptors were detected in WAT and adipocytes. CONCLUSION: Follistatin is a new adipokine important for adipogenesis. Down-regulated WAT expression of follistatin in obesity may counteract adiposity but could, by inhibiting adipogenesis, contribute to hypertrophic obesity (large fat cells) and insulin resistance.
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| 18. |
- Golosovskaia, Elena, 1993-
(författare)
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Development of in silico methods to aid chemical risk assessment : focusing on kinetic interactions in mixtures
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The environment and biota are constantly exposed to numerous chemicals through contaminated food, soil, water, and air. These chemicals can be taken up and distributed to reach sensitive tissues where they may cause various effects. Many of these chemicals lack data on their environmental and human health effects. Traditional toxicological tests relying on animal experiments are today being phased out in favor of cell-based and computational methods for early hazard detection and exposure assessment. This thesis focuses on developing computational tools for various stages of chemical risk assessment with a particular focus on bisphenols and per- and polyfluoroalkyl substances (PFAS). In Paper I, quantitative structure-activity relationship (QSAR) models covering molecular targets of the thyroid hormone (TH) system were developed and applied to two data sets to prioritize chemicals of concern for detailed toxicological studies. In Papers II and III, experimental and computational approaches were combined to study toxicokinetics and maternal transfer in zebrafish. Our main focus was to study potential mixture effects on administration, distribution, metabolism, and elimination (ADME) processes, i.e., to reveal if co-exposed chemicals impact each other’s ADME. Physiologically based kinetic (PBK) mixture models were developed to allow translation of external exposure concentrations into tissue concentrations and modelling plausible mechanisms of chemical interactions in a mixture.Main findings of this thesis are summarized as follows:• Application of QSAR models (Paper I) to two chemical inventories revealed that chemicals found in human blood could induce a large iirange of pathways in the TH system whereas chemicals used in Sweden with predicted high exposure index to consumers showed a lower likelihood to induce TH pathways.• Two zebrafish experiments (Paper II and Paper III) did not reveal statistically significant mixture effects on ADME of chemicals.• In Paper II, a PBK mixture model for PFAS accounting for competitive plasma protein binding was developed. The model demonstrated good predictive performance. Competitive plasma protein binding did not affect the predicted internal concentrations.• In Paper III we developed a binary PBK model parametrized for two bisphenols and PFOS showing that competitive plasma protein binding has an effect on ADME of bisphenols at PFOS concentrations at μg/L levels. At these levels internal concentrations of bisphenols were shown to decrease, implying that PFOS outcompeted bisphenols from studied plasma proteins resulting in higher excretion rates.Developed QSAR models showed good predictive power and the ability to identify and prioritize chemicals of concern with confidence. Additionally, PBK models aid in hypotheses testing and predicting exposure concentrations at which co-exposed chemicals could potentially influence each other’s ADME properties. These tools will provide overall early tier data on exposure and effects using non-testing methods in assessment of risks of chemicals.
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| 19. |
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| 20. |
- Jern, Stefan, et al.
(författare)
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Lundapsykologins första femtio år inom samhällsvetenskaplig fakultet
- 2015
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Ingår i: Samhällsvetenskapliga fakulteten i Lund — en vital 50-åring. En jubileumsskrift.. - 9789176233597 ; , s. 185-198
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Bokkapitel (populärvet., debatt m.m.)abstract
- A brief overview of the history of the Department of Psychology within the Faculty of Social Sciences 1964 - 2015.
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| 21. |
- Kersten, Anton, et al.
(författare)
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Electric Vehicle Heating Management Techniques utilizing Drivetrain-Loss-Heating of Refrigerant
- 2022
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Ingår i: IECON Proceedings (Industrial Electronics Conference). - 2577-1647 .- 2162-4704. ; 2022-October
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Konferensbidrag (refereegranskat)abstract
- Resistive cabin heaters can significantly reduce the driving range of battery electric vehicles in cold climate conditions. Heat pump solutions can mitigate this drawback, but these are also complemented with resistive heaters which are often unnecessary in warmer climates. This paper investigates different drivetrain-loss-heating techniques, which can be used as redundancy or as a replacement for the resistive heater. With the help of different software tools, the achievable electric drive unit (EDU) losses, considering the motor and inverter losses, of a Volkswagen ID.3 are simulated. When driving at lower speeds or standstill, the EDU losses can be regulated via the stator current magnitude. As demonstrated, this method increases the torque ripple, but the generated heat losses, varying from 5.8 kW to 7.9 kW, are sufficient to fulfill the cold climate heating requirements. When operated at standstill, a declutched motor can achieve comparable heat losses, but disconnectors are seldomly used in battery electric vehicles. When using balanced three-phase DC currents at standstill, the heat losses vary from 4.6 kW to 5.4 kW depending on the rotor position, which might not be sufficient to fulfill the required heating capacity at cold climates.
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| 22. |
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| 23. |
- Killander, Fredrika, et al.
(författare)
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Radiotherapy and tamoxifen after mastectomy in postmenopausal women - 20 year follow-up of the South Sweden Breast Cancer group randomised trial SSBCG II : I
- 2007
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 43:14, s. 2100-2108
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To evaluate long-term effects of radiotherapy and tamoxifen after mastectomy on recurrence and survival in stage II breast cancer. Methods: A randomised phase III study with three treatment alternatives. (1) Radiotherapy 50 Gy/2S fractions to chest wall and regional lymph nodes (RT). (2) Radiotherapy and tamoxifen 30 mg/day for one year (RT + tam) and 3. Tamoxifen (tam). Results: 724 postmenopausal women were included between 1978 and 1985 and the trial was close to population based. Follow-up for survival was 23 years. Locoregional recurrences were reduced from 18.5% in the tam arm to 5.3% in the RT + tam arm. Overall mortality at 20 years was 71% in the RT arm, 68% in the RT + tam arm and 62% in the tam arm. The difference between RT + tam and tam was not significant except in the receptor positive subgroup in favour of non-irradiated patients (p = 0.047). The cumulative incidence of systemic disease at 20 years was lower in the RT + Tam arm than in the RT arm, 40% versus 50% (p = 0.047). Conclusion: Postmastectomy radiotherapy significantly reduced loco-regional recurrences, but overall survival was not improved. At 20 years, a lower mortality was recorded for non-irradiated patients treated with tam. (C) 2007 Published by Elsevier Ltd.
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| 24. |
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| 25. |
- Larsson, Miriam, et al.
(författare)
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Functional studies of the yeast Med5, Med15 and Med16 mediator tail subunits
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLOS). - 1932-6203. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- The yeast Mediator complex can be divided into three modules, designated Head, Middle and Tail. Tail comprises the Med2, Med3, Med5, Med15 and Med16 protein subunits, which are all encoded by genes that are individually non-essential for viability. In cells lacking Med16, Tail is displaced from Head and Middle. However, inactivation of MED5/MED15 and MED15/MED16 are synthetically lethal, indicating that Tail performs essential functions as a separate complex even when it is not bound to Middle and Head. We have used the N-Degron method to create temperature-sensitive (ts) mutants in the Mediator tail subunits Med5, Med15 and Med16 to study the immediate effects on global gene expression when each subunit is individually inactivated, and when Med5/15 or Med15/16 are inactivated together. We identify 25 genes in each double mutant that show a significant change in expression when compared to the corresponding single mutants and to the wild type strain. Importantly, 13 of the 25 identified genes are common for both double mutants. We also find that all strains in which MED15 is inactivated show down-regulation of genes that have been identified as targets for the Ace2 transcriptional activator protein, which is important for progression through the G1 phase of the cell cycle. Supporting this observation, we demonstrate that loss of Med15 leads to a G1 arrest phenotype. Collectively, these findings provide insight into the function of the Mediator Tail module.
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| 26. |
- Lilja, Ylva, et al.
(författare)
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Effects of extended preoperative information on perioperative stress : an anaesthetic nurse intervention for patients with breast cancer and total hip replacement
- 1998
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Ingår i: Intensive & Critical Care Nursing. - Oxford : Elsevier. - 0964-3397 .- 1532-4036. ; 14:6, s. 276-282
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Tidskriftsartikel (refereegranskat)abstract
- An anaesthetic nurse intervention was performed in order to evaluate the effects of extended preoperative information, given by anaesthetic nurses, on perioperative stress in patients operated on for breast cancer or total hip replacement (THR). Forty-six consecutive patients scheduled for surgery for breast cancer, and 55 for THR, were randomized into two groups which were given different modes of preoperative information. Patients in the control group were informed about pre-and postoperative routines by a ward nurse. Patients in the intervention group were given extended formalized information by an anaesthetic nurse. Wilcoxon rank sum test was used to show relations between variables. There were no significant differences between the intervention group and control group for patients with breast cancer or for patients with THR. Breast cancer patients in the intervention group were significantly more anxious than THR patients in the intervention group (P<0.01). Breast cancer patients in the intervention group showed the highest anxiety scores on the Hospital Anxiety and Depression Scale (HADS) scale on the day of surgery. This information may reflect an increased level of anxiety due to the extended information given preoperatively. The information may thus have had a negative effect on breast cancer patients, resulting in an increased state of anxiety. The result indicates a need for individualized modes of information to provide a proper balance between enough and too much information. © 1998 Harcourt Brace & Co. Ltd.
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| 27. |
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| 28. |
- Norbeck, Ola, et al.
(författare)
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Optimizing 3D EPI for rapid T1 -weighted imaging.
- 2020
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 84:3, s. 1441-1455
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate the use of 3D EPI for rapid T1 -weighted brain imaging, focusing on the RF pulse's influence on the contrast between gray and white matter.METHODS: An interleaved 3D EPI sequence use partial Fourier and CAIPIRINHA sampling was used to acquire T1 -weighted brain volumes with isotropic resolution, low echo times, and low geometric distortions. Five different RF pulses were evaluated in terms of fat suppression performance and gray-white matter contrast. Two binomial RF pulses were compared to a single rectangular (WE-rect) RF pulse exciting only water, and two new RF pulses developed in this work, where one was an extension of the WE-rect, and the other was an SLR pulse. The technique was demonstrated in three clinical cases, where brain tumor patients were imaged before and after gadolinium administration.RESULTS: A fat-suppressed 3D EPI sequence with a phase encoding bandwidth of around 100 Hz was found to exhibit a good trade-off between geometrical distortions and scan duration. Whole-brain T1 -weighted 3D EPI images with 1.2 mm isotropic voxel size could be acquired in 24 seconds. The WE-rect, its extension, and the SLR RF pulses resulted in reduced magnetization transfer effects and provided a 20% mean increase in gray-white matter contrast.CONCLUSION: Using a high phase encoding bandwidth and RF pulses that reduce magnetization transfer effects, a fat-suppressed multi-shot 3D EPI sequence can be used to rapidly acquire isotropic T1 -weighted volumes.
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| 29. |
- Norbeck, Ola, et al.
(författare)
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T1 -FLAIR imaging during continuous head motion : Combining PROPELLER with an intelligent marker.
- 2021
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 85:2, s. 868-882
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of this work is to describe a T1 -weighted fluid-attenuated inversion recovery (FLAIR) sequence that is able to produce sharp magnetic resonance images even if the subject is moving their head throughout the acquisition.METHODS: The robustness to motion artifacts and retrospective motion correction capabilities of the PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) trajectory were combined with prospective motion correction. The prospective correction was done using an intelligent marker attached to the subject. This marker wirelessly synchronizes to the pulse sequence to measure the directionality and magnitude of the magnetic fields present in the MRI machine during a short navigator, thus enabling it to determine its position and orientation in the scanner coordinate frame. Three approaches to incorporating the marker-navigator into the PROPELLER sequence were evaluated. The specific absorption rate, and subsequent scan time, of the T1 -weighted FLAIR PROPELLER sequence, was reduced using a variable refocusing flip-angle scheme. Evaluations of motion correction performance were done with 4 volunteers and 3 types of head motion.RESULTS: During minimal out-of-plane movement, retrospective PROPELLER correction performed similarly to the prospective correction. However, the prospective clearly outperformed the retrospective correction when there was out-of-plane motion. Finally, the combination of retrospective and prospective correction produced the sharpest images even during large continuous motion.CONCLUSION: Prospective motion correction of a PROPELLER sequence makes it possible to handle continuous, large, and high-speed head motions with only minor reductions in image quality.
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| 30. |
- Nylander, Elin, et al.
(författare)
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Five-year outcomes of ADHD diagnosed in adulthood.
- 2021
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Ingår i: Scandinavian journal of psychology. - : Wiley. - 1467-9450 .- 0036-5564. ; 62:1, s. 13-24
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Tidskriftsartikel (refereegranskat)abstract
- There is a dearth of long-term follow-up studies of adults diagnosed with ADHD. Here, the aim was to evaluate long-term outcomes in a group of ADHD patients diagnosed in adulthood and receiving routine psychiatric health care. Adults diagnosed with any type of ADHD (n=52) and healthy controls (n=73) were assessed at baseline and at a 5-year follow-up, using Global Assessment of Functioning (GAF), Clinical Global Impression (CGI), Brown ADD Scale (BADDS) and Adult ADHD Self-Report Scale (ASRS). A multivariate regression method was used to identify factors predicting 5-year outcomes, including baseline ratings, medication intensity, comorbidity, intelligence quotient (IQ), age, and sex. After 5years, ADHD patients reported fewer and/or less severe symptoms compared to baseline, but remained at clinically significant symptom levels and with functional deficits. Baseline self-reports of ADHD symptoms predicted their own 5-year outcome and low baseline functioning level predicted improved global functioning at follow-up. Factors previously reported to predict short-term outcomes (i.e., medication, comorbidity, IQ, age, and sex) did not anticipate long-term outcomes in present study.
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| 31. |
- Nylander, Elin, et al.
(författare)
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The Quantified Behavioural Test Plus (QbTest plus ) in adult ADHD
- 2023
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Ingår i: Nordic Psychology. - : Informa UK Limited. - 1901-2276 .- 1904-0016. ; 75:1, s. 20-34
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Tidskriftsartikel (refereegranskat)abstract
- The Quantified Behavioural Test Plus (QbTest+) is widely used in clinical practice to assess patients with attention-deficit hyperactivity disorder (ADHD). This study mapped its behaviour in a group of adults with ADHD. Does it signal problems with impulsivity, attention and/or activity? To what extent are patients' self-reported problems reflected in QbTest performance? Does Qb testing foretell the future, as reflected in the patients' and clinicians' judgements 4 years later? We here recorded the three QbTest+ cardinals-QbActivity, QbImpulsivity and QbInattention - in 67 consecutive ADHD patients diagnosed in adulthood. Among the 54 patients who medicated as usual on the day of testing, 35 (65%) scored above the clinical cut-off (Q-score >= 1.25) on at least one of the QbTest+ cardinals. Out of the 13 patients who suspended medication prior to the test, 11 (85%) scored above the clinical cut-off on at least one of the Qb-variables. There were modest associations between QbTest+ cardinals and symptom self-ratings [Brown ADD scale (BADDS); Adult Self-Report Scale (ASRS)]. Forty-one patients completed a second QbTest+ approximately 4 years after the first. Performance was improved on the follow-up test and fewer patients scored in the clinical range (34%). The scores on the QbInattention cardinal at baseline correlated positively with BADDS and ASRS self-ratings at the 4-year follow-up.
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| 32. |
- Odille, Fabrice, et al.
(författare)
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On the characterization of dynamic supramolecular systems: A general mathematical association model for linear supramolecular copolymers and application on a complex two-component hydrogen-bonding system
- 2007
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Ingår i: Chemistry: A European Journal. - : Wiley. - 1521-3765 .- 0947-6539. ; 13:34, s. 9617-9636
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Tidskriftsartikel (refereegranskat)abstract
- A general mathematical model for the characterization of the dynamic (kinetically labile) association of supramolecular assemblies in solution is presented. It is an extension of the equal K (EK) model by the stringent use of linear algebra to allow for the simultaneous presence of an unlimited number of different units in the resulting assemblies. It allows for the analysis of highly complex dynamic equilibrium systems in solution, including both supramolecular homo- and copolymers without the recourse to extensive approximations, in a field in which other analytical methods are difficult. The derived mathematical methodology makes it possible to analyze dynamic systems such as supramolecular copolymers regarding for instance the degree of polymerization, the distribution of a given monomer in different copolymers as well as its position in an aggregate. It is to date the only general means to characterize weak supramolecular systems. The model was fitted to NMR dilution titration data by using the program Matlab((R)), and a detailed algorithm for the optimization of the different parameters has been developed. The methodology is applied to a case study, a hydrogen-bonded supramolecular system, salen 4+porphyrin 5. The system is formally a two-component system but in reality a three-component system. This results in a complex dynamic system in which all monomers are associated to each other by hydrogen bonding with different association constants, resulting in homo- and copolymers 4,,5,, as well as cyclic structures 6 and 7, in addition to free 4 and 5. The system was analyzed by extensive NMR dilution titrations at variable temperatures. All chemical shifts observed at different temperatures were used in the fitting to obtain the Delta H degrees and Delta S degrees values producing the best global fit. From the derived general mathematical expressions, system 4+5 could be characterized with respect to above-mentioned parameters.
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| 33. |
- Rautio, Elina, et al.
(författare)
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Implantable cardioverter defibrillator and cardiac resynchronization treatment in people with type 2 diabetes: a comparison with age- and sex matched controls from the general population
- 2024
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Ingår i: CARDIOVASCULAR DIABETOLOGY. - 1475-2840. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIncreased risk of severe tachyarrhythmias is reported in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to explore if treatment with cardiac implantable electronic device (CIED) such as implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy- pacemaker and -defibrillator (CRT-P/CRT-D) differed in patients with vs. without T2DM. A secondary aim was to identify patient characteristics indicating an increased CIED treatment.Method416 162 adult patients with T2DM from the Swedish National Diabetes Registry and 2 081 087 controls from the Swedish population, matched for age, sex and living area, were included between 1/1/1998 and 31/12/2012 and followed until 31/12/2013. They were compared regarding prevalence of ventricular tachycardia (VT) at baseline and the risk of receiving a CIED during follow-up. Multivariable Cox regression analysis was performed to estimate the risk of CIED-treatment and factors identifying patients with such risk.ResultsVentricular fibrillation (VF) (0.1% vs 0.0004%) and (VT) (0.2% vs. 0.1%) were more frequent among patients with T2DM compared to controls. CIED-treatment was significantly increased in patients with T2DM both in unadjusted and adjusted analyses. HR and 95% CI, after adjustment for sex, age, marital status, income, education, country of birth, coronary artery disease and congestive heart failure, were 1.32 [1.21-1.45] for ICD, 1.74 [1.55-1.95] for CRT-P and 1.69 [1.43-1.99] for CRT-D. Blood-pressure and lipid lowering therapies were independent risk factors associated to receiving CIED, while female sex was protective.ConclusionsAlthough the proportion of VT/VF was low, patients with T2DM had a higher prevalence of these conditions and increased risk for treatment with CIED compared to controls. This underlines the importance of recognizing that T2DM patients have an increased need of CIED.
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| 34. |
- Rautio, E., et al.
(författare)
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Patients With Type 2 Diabetes Have an Increased Demand for Pacemaker Treatment: A Comparison With Age- and Sex-Matched Control Subjects From the General Population
- 2020
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Ingår i: Diabetes care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 43:11, s. 2853-2858
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Patients with type 2 diabetes have an increased risk for cardiovascular disease, including arrhythmias. The prevalence of bradyarrhythmia and the subsequent need for treatment with pacemakers (PMs) is less well explored in a contemporary patient population. The current study explores1) whether patients with type 2 diabetes have an increased demand for PM implantation compared with an age- and sex-matched control population without diabetes and2) patient characteristics associated with an increased demand for receiving a PM. RESEARCH DESIGN AND METHODS In this population-matched registry study, a total of 416,247 patients with type 2 diabetes from the Swedish National Diabetes Registry and 2,081,235 age- and sex-matched control subjects selected from the general population were included between 1 January 1998 and 31 December 2012 and followed until 31 December 2013. Mean follow-up time was 7 years. Cox proportional hazards regression analyses were performed to estimate the demand of PM treatment and the factors identifying patients with such demand. RESULTS Type 2 diabetes was associated with an increased need of PM treatment (hazard ratio 1.65 [95% CI 1.60-1.69];P< 0.0001), which remained (1.56 [1.51-1.60];P< 0.0001) after adjustments for age, sex, educational level, marital status, country of birth, and coronary heart disease. Risk factors for receiving a PM included increasing age, HbA(1c), BMI, diabetes duration, and lipid- and blood pressure-lowering medication. CONCLUSIONS The need for PM treatment is higher in patients with type 2 diabetes than in matched population-based control subjects. Age, diabetes duration, and HbA(1c)seem to be risk factors for PM treatment.
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| 35. |
- Ritsinger, V., et al.
(författare)
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Elevated levels of adipokines predict outcome after acute myocardial infarction : A long-term follow-up of the Glucose Tolerance in Patients with Acute Myocardial Infarction cohort
- 2017
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Ingår i: Diabetes & Vascular Disease Research. - : Sage Publications. - 1479-1641 .- 1752-8984. ; 14:2, s. 77-87
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Adiponectin and leptin are associated with insulin resistance and cardiovascular disease. Information on the prognostic value after an acute myocardial infarction is still conflicting. Methods: Patients (n = 180) without known diabetes and with admission glucose of <11 mmol/L admitted for an acute myocardial infarction in 1998-2000 were followed for mortality and cardiovascular events (first of cardiovascular mortality/acute myocardial infarction/stroke/heart failure) until the end of 2011 (median: 11.6 years). Plasma adiponectin and leptin were related to outcome in Cox proportional-hazard regression analyses. Results: Median age was 64 years and 69% were male. Total mortality was 34% (n = 61) and 44% (n = 80) experienced a cardiovascular event. Adiponectin at discharge predicted cardiovascular events (hazard ratio; 95% confidence interval; 1.45; 1.02-2.07, p = 0.038), total mortality (2.53; 1.64-3.91, p < 0.001) and cancer mortality (3.64; 1.51-8.74, p = 0.004). After adjustment for age, sex, body mass index, previous myocardial infarction and heart failure, adiponectin predicted total mortality (1.79; 1.07-3.00, p = 0.027) but not cardiovascular events. High levels of leptin were associated with cardiovascular events during the first 7 years, after which the association was attenuated. Leptin did not predict total mortality. Conclusion: In patients with acute myocardial infarction but without previously known diabetes, high levels of adiponectin at discharge predicted total mortality. The present results support the hypothesis that high rather than low levels of adiponectin predict mortality after acute myocardial infarction.
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| 36. |
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| 37. |
- Ritsinger, V., et al.
(författare)
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Elevated levels of insulin-like growth factor-binding protein 1 predict outcome after acute myocardial infarction : A long-term follow-up of the glucose tolerance in patients with acute myocardial infarction (GAMI) cohort
- 2018
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Ingår i: Diabetes & Vascular Disease Research. - : SAGE Publications Ltd. - 1479-1641 .- 1752-8984. ; 15:5, s. 387-395
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the long-term prognostic value of insulin-like growth factor-binding protein 1 in patients with acute myocardial infarction. Methods: Patients (n = 180) with admission glucose < 11 mmol/L without previously known diabetes admitted for an acute myocardial infarction in 1998–2000 were followed for mortality and cardiovascular events (first of cardiovascular mortality/acute myocardial infarction/stroke/severe heart failure) until the end of 2011 (median 11.6 years). Fasting levels of insulin-like growth factor-binding protein 1 at day 2 were related to outcome in Cox proportional hazard regression analyses. Results: Median age was 64 years, 69% were male and median insulin-like growth factor-binding protein 1 was 20 µg/L. Total mortality was 34% (n = 61) and 44% (n = 80) experienced a cardiovascular event during a median follow-up time of 11.6 years. After age adjustment, insulin-like growth factor-binding protein 1 was associated with all-cause (1.40; 1.02–1.93, p = 0.039) and cancer mortality (2.09; 1.15–3.79, p = 0.015) but not with cardiovascular death (p = 0.29) or cardiovascular events (p = 0.57). After adjustments also for previous myocardial infarction, previous heart failure and body mass index, insulin-like growth factor-binding protein 1 was still associated with all-cause mortality (1.38; 1.01–1.89, p = 0.046). Conclusion: In patients with acute myocardial infarction without previously known diabetes, high insulin-like growth factor-binding protein 1 was associated with long-term all-cause and cancer mortality but not with cardiovascular events.
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| 38. |
- Rydén, Henric, et al.
(författare)
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Chemical shift encoding using asymmetric readout waveforms.
- 2021
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 85:3, s. 1468-1480
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To describe a new method for encoding chemical shift using asymmetric readout waveforms that enables more SNR-efficient fat/water imaging.METHODS: Chemical shift was encoded using asymmetric readout waveforms, rather than conventional shifted trapezoid readouts. Two asymmetric waveforms are described: a triangle and a spline. The concept was applied to a fat/water separated RARE sequence to increase sampling efficiency. The benefits were investigated through comparisons to shifted trapezoid readouts. Using asymmetric readout waveforms, the scan time was either shortened or maintained to increase SNR. A matched in-phase waveform is also described that aims to improve the SNR transfer function of the fat and water estimates. The sequence was demonstrated for cervical spine, musculoskeletal (MSK), and optic nerve applications at 3T and compared with conventional shifted readouts.RESULTS: blurring. Maintaining the scan times and using asymmetric readout waveforms achieved an SNR improvement in agreement with the prolonged sampling duration.CONCLUSIONS: Asymmetric readout waveforms offer an additional degree of freedom in pulse sequence designs where chemical shift encoding is desired. This can be used to significantly shorten scan times or to increase SNR with maintained scan time.
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| 39. |
- Rydén, Henric, et al.
(författare)
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RARE two-point Dixon with dual bandwidths.
- 2020
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 84:5, s. 2456-2468
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate the impact of dual readout bandwidths (dBW) in a dual echo fat/water acquisition and describe a dBW-rapid acquisition relaxation enhanced, or turbo spin echo sequence where the concept is used to improve SNR by removing dead times between refocusing pulses and avoiding redundant Chemical-shift encoded.METHODS: Cramér-Rao bounds and Monte Carlo simulations were used to investigate a two-point fat/water model where the difference in bandwidths is incorporated. In vivo images were acquired at 1.5 and 3 T with the dBW-rapid acquisition relaxation enhanced, or turbo spin echo sequence. Typical bandwidth ratios were 1:2. SNR was compared with a single bandwidth sequence under identical scan parameters at 3T.RESULTS: Monte Carlo simulations and Cramér-Rao analysis demonstrate that number of signal averages can be improved with dual bandwidths compared to conventional single bandwidth acquisitions. The dBW-rapid acquisition relaxation enhanced, or turbo spin echo sequence can acquire images with high readout resolutions with well-conditioned sampling. An SNR improvement of 52% was measured, in line with the theoretical gain of 54%.CONCLUSIONS: The proposed dBW-rapid acquisition relaxation enhanced, or turbo spin echo sequence is a highly SNR-efficient two-point rapid acquisition relaxation enhanced, or turbo spin echo sequence without dead times, and can acquire images at higher resolutions than current vendor-supplied alternatives.
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| 40. |
- Rydén, Henric, et al.
(författare)
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T1 weighted fat/water separated PROPELLER acquired with dual bandwidths.
- 2018
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 80:6, s. 2501-2513
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To describe a fat/water separated dual receiver bandwidth (rBW) spin echo PROPELLER sequence that eliminates the dead time associated with single rBW sequences. A nonuniform noise whitening by regularization of the fat/water inverse problem is proposed, to enable dual rBW reconstructions.METHODS: Bipolar, flyback, and dual spin echo sequences were developed. All sequences acquire two echoes with different rBW without dead time. Chemical shift displacement was corrected by performing the fat/water separation in k-space, prior to gridding. The proposed sequences were compared to fat saturation, and single rBW sequences, in terms of SNR and CNR efficiency, using clinically relevant acquisition parameters. The impact of motion was investigated.RESULTS: Chemical shift correction greatly improved the image quality, especially at high resolution acquired with low rBW, and also improved motion estimates. SNR efficiency of the dual spin echo sequence was up to 20% higher than the single rBW acquisition, while CNR efficiency was 50% higher for the bipolar acquisition. Noise whitening was deemed necessary for all dual rBW acquisitions, rendering high image quality with strong and homogenous fat suppression.CONCLUSION: Dual rBW sequences eliminate the dead time present in single rBW sequences, which improves SNR efficiency. In combination with the proposed regularization, this enables highly efficient T1-weighted PROPELLER images without chemical shift displacement.
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| 41. |
- Rydén, Ingvar, et al.
(författare)
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Diagnostic accuracy of a1-acid glycoprotein fucosylation for liver cirrhosis in patients undergoing hepatic biopsy
- 2002
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Ingår i: Clinical Chemistry. - 0009-9147 .- 1530-8561. ; 48:12, s. 2195-2201
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Tidskriftsartikel (refereegranskat)abstract
- Background: Increased fucosylation of serum glycoproteins has previously been reported in patients with liver disease. We analyzed a1-acid glycoprotein (AGP) fucosylation in serum samples from patients investigated for suspected liver disease to evaluate its value as a biochemical marker for liver cirrhosis. Methods: We used a novel lectin immunoassay adapted to the AutoDELFIA system to analyze AGP fucosylation in 261 consecutive patients admitted for liver biopsy at Malm÷ University Hospital in Southern Sweden. The results were compared with histopathologic findings. In addition, AGP fucosylation was compared with other biochemical markers described as useful in the diagnosis of liver cirrhosis. The biochemical markers were compared by ROC curve analysis. Results: AGP fucosylation was significantly (P <0.05) higher in patients with liver cirrhosis (n = 65) than in healthy controls (n = 72), patients with normal histology (n = 29), patients with steatosis only (n = 38), patients with viral or chronic hepatitis without cirrhosis (n = 71), and patients with other liver diseases without histologic signs of cirrhosis (n = 58). By calculating the AGP fucosylation index (AGP-FI = AGP fucosylation/AGP serum concentration), we obtained a high diagnostic accuracy. The areas under the ROC curves for AGP-FI were 0.83 and 0.74 for men and women, respectively, compared with 0.82 for hyaluronic acid and 0.77 for the aspartate aminotransferase/alanine aminotransferase ratio in both men and women. Conclusions: AGP fucosylation appears to be useful in identifying patients with liver cirrhosis among patients investigated for liver disease. The lectin immunoassay showed satisfactory reproducibility and is suitable for routine use in a clinical laboratory.
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| 42. |
- Rydén, Ingvar, et al.
(författare)
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Increased α1-acid glycoprotein fucosylation in patients with liver cirrhosis
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Increased fucosylation of serum glycoproteins has previously been reported in patients with liver disease. We analyzed α1-acid glycoprotein (AGP) fucosylation in serum samples from patients investigated for suspected liver disease, in order to evaluate its value as a biochemical marker for liver cirrhosis.Methods: We used a novel lectin innnunoassay adapted to the Auto-DELFIA system to analyze AGP fucosylation in 261 consecutive patients admitted for liver biopsy at Malmö university hospital in Southern Sweden. The results were compared with histopathological findings. In addition, AGP fucosylation was compared to other biochemical markers described to be useful in the diagnosis of liver cirrhosis. The different biochemical markers were compared by ROC curve analysis.Results: AGP fucosylation was significantly higher in patients with liver cirrhosis (n=65) than in nmmal controls (n=72), patients with normal histology (n=29), patients with steatosis only (n=38), patients with viral or chronic hepatitis without ciiThosis (n=71), and patients with other liver diseases without histological signs of cirrhosis (n=58). By calculating an AGP fucosylation index (AGP-FI = AGP fucosylation/AGP serum concentration), a high diagnostic accuracy was obtained. The area under the curve for AGP-FI was 0.83 and 0.74 for men and women respectively, compared to 0.82 for hyaluronic acid, and 0.77 for AST/ALT ratio in both men and women.Conclusion: We conclude that AGP fucosylation appears to be useful in identifying patients with liver cirrhosis among patients investigated for liver disease. The lectin immunoassay showed satisfactory reproducibility, and is suitable for routine use in a clinical laboratory.
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| 43. |
- Rydén, Lars, et al.
(författare)
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ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:39, s. 3035-3087
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Tidskriftsartikel (refereegranskat)abstract
- This is the second iteration of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) joining forces to write guidelines on the management of diabetes mellitus (DM), pre-diabetes, and cardiovascular disease (CVD), designed to assist clinicians and other healthcare workers to make evidence-based management decisions. The growing awareness of the strong biological relationship between DM and CVD rightly prompted these two large organizations to collaborate to generate guidelines relevant to their joint interests, the first of which were published in 2007. Some assert that too many guidelines are being produced but, in this burgeoning field, five years in the development of both basic and clinical science is a long time and major trials have reported in this period, making it necessary to update the previous Guidelines.
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| 44. |
- Rydén, Lisa, et al.
(författare)
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Tumor-specific VEGF-A and VEGFR2 in postmenopausal breast cancer patients with long-term follow-up : Implication of a link between VEGF pathway and tamoxifen response
- 2005
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Ingår i: Breast Cancer Research and Treatment. - The Hague : Nijhoff. - 0167-6806 .- 1573-7217. ; 89:2, s. 135-143
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor (VEGF-A) is considered a prognostic indicator for clinical outcome in breast cancer. Conflicting results nevertheless exist and there is a need for larger studies including untreated patients in order to clarify the importance of tumor-specific VEGF-A regarding prognosis as well as potential links to predictive treatment information. VEGF-A and its receptor, vascular endothelial growth receptor 2 (VEGFR2), were therefore analyzed by immunohistochemistry in postmenopausal breast cancers enrolled in a clinical trial where patients were randomized to adjuvant tamoxifen treatment (n=124) for 2 years or no treatment (n=127) with a median follow-up of 18 years. The tumors were arranged in a tumor tissue microarray system enabling parallell analysis of the angiogenic factors and hormone receptor status. Tumor-specific expression of VEGFR2 correlated strongly with expression of VEGF-A and progesterone receptor (PR) negativity, whereas VEGF-A was not associated with hormone receptor status. Among patients with estrogen receptor (ER) positive (fraction > 10%) tumors, there was a statistically significant tamoxifen response in VEGF-A negative tumors at both 10-year and 18-year disease-free survival (DFS), contrasting to VEGF-A positive tumors who had no beneficial effect of tamoxifen. A treatment-interaction variable indicated a marked difference in tamoxifen response depending on VEGFA-status in terms of DFS at 10 and 18 years of follow-up, p=0.046 and p=0.039, respectively. VEGFR2 status did not yield significant predicitve information for tamoxifen response in patients with ER fraction > 10%, whereas in patients with ER fraction > 90% both VEGF-A and VEGFR2 status were associated with tamoxifen treatment effect.
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| 45. |
- Rydén, Stefan, et al.
(författare)
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A scintillation camera technique for measurements of the reticuloendothelial function -Comparison of different methods for measuring RES function
- 1982
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Ingår i: European Journal Of Nuclear Medicine. - 0340-6997. ; 7, s. 16-21
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Tidskriftsartikel (refereegranskat)abstract
- A highly standardized 99mTc-sulphur colloid was used to evaluate reticuloendothelial system (RES)-function in the normal rat and after RE blockade by gelatin (Haemaccel). Activity distribution in the animals was measured with a scintillation camera technique. Total uptake of activity in the liver was estimated. From the time-activity curves over the liver, the phagocytic index (kphag) was evaluated. Estimation of the uptake rate of the labelled colloid into the liver and into other parts of the RES was also performed using a twocompartment model. Different methods of evaluation of RE function were compared. It was shown that for a proper estimation of the RE function, the whole uptake curve must be considered. Gelatin (Haemaccel) significantly reduced the total colloid uptake by the liver. The colloid uptake rate into the liver was also significantly reduced. Liver specimens after colloid injection were examined by light and electron microscopy showing vacuolation of hepatocytes and sinusoidal cells probably due to pinocytosis. The technique described enables functional studies of the RES. It has the advantage of noninvasive registrations and is based on the same technical facilities as used for routine liver scintigraphy.
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| 46. |
- Sjodin, Andreas, et al.
(författare)
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UPSC-BASE - Populus transcriptomics online
- 2006
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Ingår i: The Plant Journal. - Oxford : Blackwell. - 0960-7412 .- 1365-313X. ; 48:5, s. 806-817
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Tidskriftsartikel (refereegranskat)abstract
- The increasing accessibility and use of microarrays in transcriptomics has accentuated the need for purpose-designed storage and analysis tools. Here we present UPSC-BASE, a database for analysis and storage of Populus DNA microarray data. A microarray analysis pipeline has also been established to allow consistent and efficient analysis (from small to large scale) of samples in various experimental designs. A range of optimized experimental protocols is provided for each step in generating the data. Within UPSC-BASE, researchers can perform standard and advanced microarray analysis procedures in a user-friendly environment. Background corrections, normalizations, quality-control tools, visualizations, hypothesis tests and export tools are provided without requirements for expert-level knowledge. Although the database has been developed primarily for handling Populus DNA microarrays, most of the tools are generic and can be used for other types of microarray. UPSC-BASE is also a repository of Populus microarray information, providing data from 21 experiments on a total of 407 microarray hybridizations in the public domain of the database. There are also an additional 10 experiments containing 347 hybridizations, where the automatically analysed data are searchable.
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| 47. |
- Sprenger, Tim, et al.
(författare)
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NeuroMix-A single-scan brain exam
- 2022
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Ingår i: Magnetic Resonance in Medicine. - : Wiley-Blackwell. - 0740-3194 .- 1522-2594. ; 87:5, s. 2178-2193
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Implement a fast, motion-robust pulse sequence that acquires T1 -weighted, T2 -weighted, T2 * -weighted, T2 fluid-attenuated inversion recovery, and DWI data in one run with only one prescription and one prescan.METHODS: A software framework was developed that configures and runs several sequences in one main sequence. Based on that framework, the NeuroMix sequence was implemented, containing motion robust single-shot sequences using EPI and fast spin echo (FSE) readouts (without EPI distortions). Optional multi-shot sequences that provide better contrast, higher resolution, or isotropic resolution could also be run within the NeuroMix sequence. An optimized acquisition order was implemented that minimizes times where no data is acquired.RESULTS: NeuroMix is customizable and takes between 1:20 and 4 min for a full brain scan. A comparison with the predecessor EPIMix revealed significant improvements for T2 -weighted and T2 fluid-attenuated inversion recovery, while taking only 8 s longer for a similar configuration. The optional contrasts were less motion robust but offered a significant increase in quality, detail, and contrast. Initial clinical scans on 1 pediatric and 1 adult patient showed encouraging image quality.CONCLUSION: The single-shot FSE readouts for T2 -weighted and T2 fluid-attenuated inversion recovery and the optional multishot FSE and 3D-EPI contrasts significantly increased diagnostic value compared with EPIMix, allowing NeuroMix to be considered as a standalone brain MRI application.
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| 48. |
- Stendahl, Maria, et al.
(författare)
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Cyclin D1 overexpression is a negative predictive factor for tamoxifen response in postmenopausal breast cancer patients
- 2004
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Ingår i: British Journal of Cancer. - London : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 90:10, s. 1942-1948
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Tidskriftsartikel (refereegranskat)abstract
- Antioestrogen treatment by tamoxifen is a well-established adjuvant therapy for oestrogen receptor-alpha (ER) positive breast cancer. Despite ER expression some tumours do not respond to tamoxifen and we therefore delineated the potential link between the cell cycle regulator and ERco-factor, cyclin D1, and tamoxifen response in a material of 167 postmenopausal breast cancers arranged in a tissue array. The patients had been randomised to 2 years of tamoxifen treatment or no treatment and the median follow-up time was 18 years. Interestingly in the 55 strongly ERpositive samples with moderate or low cyclin D1 levels, patients responded to tamoxifen treatment whereas the 46 patients with highly ER positive and cyclin D1 overexpressing tumours did not show any difference in survival between tamoxifen and no treatment. Survival in untreated patients with cyclin D1 high tumours was slightly better than for patients with cyclin D1 low/moderate tumours. However, there was a clearly increased risk of death in the cyclin D1 high group compared to an age-matched control population. Our results suggest that cyclin D1 overexpression predicts for tamoxifen treatment resistance in breast cancer, which is line with recent experimental data using breast cancer cell lines and overexpression systems.
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| 49. |
- Stenman, Emelie, et al.
(författare)
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Diagnostic center for primary care patients with nonspecific symptoms and suspected cancer : compliance to workflow and accuracy of tests and examinations
- 2021
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Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 39:2, s. 148-156
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate compliance to workflow and accuracy of tests in Sweden's first fast-track referral pathway for patients with nonspecific symptoms and suspected cancer (SCAN).DESIGN: Prospective cohort study with consecutive inclusion of patients referred to the diagnostic center (DC).SETTING: Patients with nonspecific symptoms were examined in primary care according to a protocol including two test packages and diagnostic imaging. If symptoms were not explained, patients were referred to the DC and a DC-test package was taken. At the DC, further investigations resulted in diagnosis/no diagnosis.SUBJECTS: A total of 290 patients, median age 69 years (interquartile range [IQR] 59-76), 48% men, participated. A total of 64 (22%) were diagnosed with cancer, 186 (64%) with non-malignant disease and 40 (14%) had no new disease.MAIN OUTCOME MEASURE: Compliance was estimated by percentage of compulsory tests taken. Test accuracy was assessed by likelihood ratios (LRs) regarding cancer.RESULTS: A total of 23 (8%) patients had taken both primary care packages, whereas 150 (52%) patients went through entire diagnostic imaging. Abnormal pulmonary X-ray, peak expiratory flow (PEF) and calcium had the highest LRs in primary care (3.5; 3.2; 2.7). A total of 105 (36%) took the complete DC-package, of which bilirubin and cytomegalovirus had the highest LRs (11.5; 10.9). The median number (IQR) of abnormal primary care tests was 5 (3-6) for cancer, 3 (2-6) for other diagnoses and 1 (0-3) for no diagnosis.CONCLUSIONS: Compliance to test packages in primary care was low, which warrants review of the workflow. Few single tests had high accuracy regarding cancer, but the number of abnormal tests can provide guidance in complicated investigations of suspected malignancies.KEY POINTSFast-track referral pathways for patients with nonspecific serious symptoms have been implemented in several countries and are part of the national cancer strategy in all of Scandinavia.Compliance with compulsory tests in primary care was modest in this study; 8% of the patients had taken the entire compulsory test packages.Few single compulsory tests had high accuracy regarding subsequent cancer, which warrants a review of tests and examinations. However, patients diagnosed with cancer had a higher number of abnormal test results compared to the other groups.
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| 50. |
- Stenman, Emelie, et al.
(författare)
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Diagnostic spectrum and time intervals in Sweden's first diagnostic center for patients with nonspecific symptoms of cancer
- 2019
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 58:3, s. 296-305
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fast-track referral is an increasingly used method for diagnostic evaluation of patients suspected of having cancer. This approach is challenging and not used as often for patients with only nonspecific symptoms. In order to expedite the diagnostics for these patients, we established Sweden's first Diagnostic Center (DC) focusing on outcomes related to diagnoses and diagnostic time intervals.MATERIAL AND METHODS: The study was designed as a prospective cohort study. Patients aged ≥18 years who presented in primary care with nonspecific symptoms of a serious disease were eligible for referral to the DC after having completed an initial investigation. Acceptable diagnostic time intervals were defined to be a maximum of 15 days in primary care and 22 days at the DC. Diagnostic outcome, length of diagnostic time intervals and patient satisfaction were evaluated.RESULTS: A total of 290 patients were included in the study. Cancer was diagnosed in 22.1%, other diseases in 64.1%, and no diagnosis was identified in 13.8% of these patients. Patients diagnosed with cancer were older, had shorter patient interval (time from first symptom to help-seeking), shorter DC-interval (time from referral decision in primary care to diagnosis) and showed a greater number of symptoms compared to patients with no diagnosis. The median primary care interval was 21 days and the median DC interval was 11 days. Few symptoms, no diagnosis, female sex, longer patient interval, and incomplete investigations were associated with prolonged diagnostic time intervals. Patient satisfaction was high; 86% of patients reported a positive degree of satisfaction with the diagnostic procedures.CONCLUSIONS: We demonstrated that the DC concept is feasible with a diagnosis reached in 86.2% of the patients in addition to favorable diagnostic time intervals at the DC and a high degree of patient satisfaction.
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