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| 4. |
- Tirri, M E, et al.
(författare)
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Two-photon excitation in fluorescence polarization receptor-ligand binding assay
- 2005
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Ingår i: Journal of Biomolecular Screening. - : Elsevier BV. - 1087-0571. ; 10:4, s. 314-319
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Tidskriftsartikel (refereegranskat)abstract
- Fluorescence polarization is one of the most commonly used homogeneous assay principles in drug discovery for screening of potential lead compounds. In this article, the fluorescence polarization technique is combined with 2-photon excitation of fluorescence. Theoretically, the use of 2-photon excitation of fluorescence increases the volumetric sensitivity and polarization contrast of fluorescence polarization assays. The work in this report demonstrates these predictions for an estrogen receptor ligand binding assay.
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| 5. |
- Toivonen, P, et al.
(författare)
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Cavum septum pellucidum and psychopathy
- 2013
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Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 203:2, s. 152-153
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Tidskriftsartikel (refereegranskat)abstract
- The presence of cavum septum pellucidum (CSP) has been reported to be a neurodevelopmental marker of psychopathy. We scanned 26 violent offenders and 25 controls; 2 offenders and 2 controls had CSP (8% in both groups). Thus, the presence of CSP is not a common or a unique feature of antisocial personality disorder or psychopathy.
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| 7. |
- Connolly, Stuart J., et al.
(författare)
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The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study
- 2013
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 128:3, s. 237-243
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Tidskriftsartikel (refereegranskat)abstract
- Background During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. Conclusions During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death.
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| 9. |
- Jolma, A, et al.
(författare)
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Multiplexed massively parallel SELEX for characterization of human transcription factor binding specificities
- 2010
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 20:6, s. 861-873
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Tidskriftsartikel (refereegranskat)abstract
- The genetic code—the binding specificity of all transfer-RNAs—defines how protein primary structure is determined by DNA sequence. DNA also dictates when and where proteins are expressed, and this information is encoded in a pattern of specific sequence motifs that are recognized by transcription factors. However, the DNA-binding specificity is only known for a small fraction of the ∼1400 human transcription factors (TFs). We describe here a high-throughput method for analyzing transcription factor binding specificity that is based on systematic evolution of ligands by exponential enrichment (SELEX) and massively parallel sequencing. The method is optimized for analysis of large numbers of TFs in parallel through the use of affinity-tagged proteins, barcoded selection oligonucleotides, and multiplexed sequencing. Data are analyzed by a new bioinformatic platform that uses the hundreds of thousands of sequencing reads obtained to control the quality of the experiments and to generate binding motifs for the TFs. The described technology allows higher throughput and identification of much longer binding profiles than current microarray-based methods. In addition, as our method is based on proteins expressed in mammalian cells, it can also be used to characterize DNA-binding preferences of full-length proteins or proteins requiring post-translational modifications. We validate the method by determining binding specificities of 14 different classes of TFs and by confirming the specificities for NFATC1 and RFX3 using ChIP-seq. Our results reveal unexpected dimeric modes of binding for several factors that were thought to preferentially bind DNA as monomers.
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| 11. |
- Morin, D. P., et al.
(författare)
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QRS duration predicts sudden cardiac death in hypertensive patients undergoing intensive medical therapy: the LIFE study
- 2009
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Ingår i: European Heart Journal. - 1522-9645. ; 30:23, s. 2908-14
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To determine whether QRS duration predicts sudden cardiac death (SCD) in patients with left ventricular hypertrophy and treated hypertension. METHODS AND RESULTS: Over 4.8 +/- 0.9 years follow-up of 9193 hypertensive patients with electrocardiographic evidence of LVH who were treated with atenolol- or losartan-based regimens, 178 patients (1.9%) suffered SCD. In multivariable analysis including randomized treatment, changing blood pressure over time, and baseline differences between patients with and without SCD, QRS duration was independently predictive of SCD (HR per 10 ms increase = 1.22, P < 0.001). Baseline QRS duration remained a significant predictor of SCD even after controlling for the presence or absence of left bundle branch block (HR = 1.17, P = 0.001) and for changes in ECG LVH severity over the course of the study (HR = 1.16, P = 0.017). CONCLUSION: In the setting of aggressive antihypertensive therapy, prolonged QRS duration identifies hypertensive patients at higher risk for SCD, even after controlling for left bundle branch block, other known risk factors for SCD, and changes in blood pressure and severity of left ventricular hypertrophy.
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| 14. |
- Okin, P. M., et al.
(författare)
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Electrocardiographic strain pattern and prediction of cardiovascular morbidity and mortality in hypertensive patients
- 2004
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Ingår i: Hypertension. - 1524-4563. ; 44:1, s. 48-54
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Tidskriftsartikel (refereegranskat)abstract
- The ECG strain pattern of lateral ST depression and T-wave inversion is a marker for left ventricular hypertrophy (LVH) and adverse prognosis in population studies. However, whether ECG strain is an independent predictor of cardiovascular (CV) morbidity and mortality in the setting of aggressive antihypertensive therapy is unclear. ECGs were examined at study baseline in 8854 hypertensive patients with ECG LVH who were treated in a blinded manner with atenolol- or losartan-based regimens. Strain was defined by the presence of a downsloping convex ST segment with an inverted asymmetrical T wave opposite to the QRS axis in leads V5 and/or V6 and was present in 971 patients (11.0%). The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study composite end point of CV death or nonfatal myocardial infarction or stroke occurred in 1035 patients (11.7%). In Cox analyses adjusting only for treatment effect, ECG strain was a significant predictor of CV death (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.78 to 2.86), fatal/nonfatal myocardial infarction (HR 2.16, 95% CI 1.67 to 2.80), fatal/nonfatal stroke (HR 1.76, 95% CI 1.39 to 2.21), and the composite CV end point (HR 1.99, 95% CI 1.70 to 2.33). After further adjusting for standard CV risk factors, baseline blood pressure, and severity of ECG LVH, ECG strain remained a significant predictor of CV mortality (HR 1.53, 95% CI 1.18 to 2.00), myocardial infarction (HR 1.55, 95% CI 1.16 to 2.06), and the composite CV end point (HR 1.33, 95% CI 1.11 to 1.59). Thus, ECG strain is a marker of increased CV risk in hypertensive patients in the setting of aggressive blood pressure lowering, independent of baseline severity of ECG LVH.
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| 15. |
- Okin, P. M., et al.
(författare)
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Electrocardiographic strain pattern and prediction of new-onset congestive heart failure in hypertensive patients: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study
- 2006
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Ingår i: Circulation. - 1524-4539. ; 113:1, s. 67-73
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The ECG strain pattern of ST depression and T-wave inversion is strongly associated with left ventricular hypertrophy (LVH) independently of coronary heart disease and with an increased risk of cardiovascular morbidity and mortality in hypertensive patients. However, whether ECG strain is an independent predictor of new-onset congestive heart failure (CHF) in the setting of aggressive antihypertensive therapy in unclear. METHODS AND RESULTS: The relationship of ECG strain at study baseline to the development of CHF was examined in 8696 patients with no history of CHF who were enrolled in the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study. All patients had ECG LVH by Cornell product and/or Sokolow-Lyon voltage criteria on a screening ECG, were treated in a blinded manner with atenolol- or losartan-based regimens, and were followed up for a mean of 4.7+/-1.1 years. Strain was defined as a downsloping convex ST segment with inverted asymmetrical T-wave opposite the QRS axis in lead V5 or V6. ECG strain was present in 923 patients (10.6%), and new-onset CHF occurred in 265 patients (3.0%), 26 of whom had a CHF-related death. Compared with patients who did not develop CHF, hypertensive patients who developed CHF were older; were more likely to be black, current smokers, and diabetic; were more like to have a history of myocardial infarction, ischemic heart disease, stroke, or peripheral vascular disease; and had greater baseline severity of LVH by Cornell product and Sokolow-Lyon voltage, higher baseline body mass indexes, higher serum glucose levels and albuminuria, similar baseline systolic and diastolic pressures, and reductions in diastolic pressure with treatment but greater reductions in systolic pressure. In univariate Cox analyses, ECG strain was a significant predictor of new-onset CHF (hazard ratio [HR], 3.27; 95% CI, 2.49 to 4.29) and CHF mortality (HR, 4.74; 95% CI, 2.11 to 10.64). In Cox multivariable analyses adjusting for baseline differences between patients with and without new-onset CHF, in-treatment differences in systolic and diastolic pressures, Sokolow-Lyon voltage, and Cornell product, and the impact of treatment with losartan versus atenolol on outcomes, ECG strain remained a significant predictor of incident CHF (HR, 1.80; 95% CI, 1.30 to 2.48) and CHF-related death (HR, 2.78; 95% CI, 1.02 to 7.63). CONCLUSIONS: ECG strain identifies hypertensive patients at increased risk of developing CHF and dying as a result of CHF, even in the setting of aggressive blood pressure lowering.
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| 17. |
- Roth, E., et al.
(författare)
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Methodological, conceptual and sampling practices in surveying recreational fisheries in the Nordic countries : experiences of a valuation survey
- 2001
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Ingår i: Fisheries Management and Ecology. - Oxford : Blackwell Science. - 0969-997X .- 1365-2400. ; 8:4-5, s. 355-367
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The planning and initial phases of a joint Nordic project for the valuation of recreational fisheries is described. The conomic value of recreational fisheries was taken to include non-market value as well as the traditional market value. The design of the survey was similar for each country so as to facilitate future comparison. However, initially there were difficulties in defining categories of recreational fishermen in the different countries. Other background information also had to be adapted to national circumstances. National population registers were used as the sampling frames. The effect of this on the response from a valuation survey is discussed. Accessibility to population register data varies by country and so do possibilities for random sampling. Legal constrains were faced when implementing a centralised mailing system.
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| 18. |
- Schulenberg, T., et al.
(författare)
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European supercritical water cooled reactor
- 2011
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Ingår i: Nuclear Engineering and Design. - : Elsevier BV. - 0029-5493 .- 1872-759X. ; 241:9, s. 3505-3513
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Tidskriftsartikel (refereegranskat)abstract
- The High Performance Light Water Reactor (HPLWR), how the European Supercritical Water Cooled Reactor is called, is a pressure vessel type reactor operated with supercritical water at 25 MPa feedwater pressure and 500 degrees C average core outlet temperature. It is designed and analyzed by a European consortium of 10 partners and 3 active supporters from 8 Euratom member states in the second phase of the HPLWR project. Most emphasis has been laid on a core with a thermal neutron spectrum, consisting of small fuel assemblies in boxes with 40 fuel pins each and a central water box to improve the neutron moderation despite the low coolant density. Peak cladding temperatures of the fuel rods have been minimized by heating up the coolant in three steps with intermediate coolant mixing. The containment design with its safety and residual heat removal systems is based on the latest boiling water reactor concept, but with different passive high pressure coolant injection systems to cause a forced convection through the core. The design concept of the steam cycle is indicating the envisaged efficiency increase to around 44%. Moreover, it provides the constraints to design the components of the balance of the plant. The project is accompanied by numerical studies of heat transfer of supercritical water in fuel assemblies and by material tests of candidate cladding alloys, performed by the consortium and supported by additional tests of the Joint Research Centre of the European Commission. Besides the scientific and technical progress, the HPLWR project turned out to be most successful in training the young generation of nuclear engineers in the technologies of light water reactors. More than 20 bachelor or master theses and more than 10 doctoral theses on HPLWR technologies have been submitted at partner organizations of this consortium since the start of this project.
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| 19. |
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| 20. |
- Toivonen, A. -L., et al.
(författare)
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The economic value of recreational fisheries in Nordic countries
- 2004
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Ingår i: Fisheries Management and Ecology. - Oxford : Blackwell Publishing. - 0969-997X .- 1365-2400. ; 11:1, s. 1-14
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Recreational fishing, wether free or at cost, has an economic value. This value was measured in five Nordic countries based on a contingent valuation mail survey. Regression models were used to identify demographic characteristics, types of fishing patterns and differences in the countries' mangement regimes that can explain both actual fishing expenditure and willingness to pay for the non-market benefits by persons participating in fishing or enjoying the benefits derived by it. Net benefit, i.e. willingness to pay over and above actual expenditure was highest amongst those fishing. In Denmark, the small number of generalist fishermen get the highest benefit. In Finland results are mixed but sports fishermen benefit on average even more than generalists. Urban sports fishing raises the highest benefit in Iceland while in Norway the benefit is more equally spread, with occasional anglers and woman reaping the least. In Sweden the mean benefit is the lowest in the Nordic countries but evenly distributed among categories of fishermen. In the Nordic countries combined, nationality explains willingness to pay as being Norwegian or Finnish increases benefit and being Icelandic reduces it. The non-use value of recreational fisheries was elicited through posing questions on willingness to pay for the preservation of the existence of current fish stocks and current quality of recreational fishing to persons participating in fishing or enjoying the benefits derived from it. For those not fishing or people in general, the power of the models to explain willingness to pay for the existence of recreational fisheries was very weak. The benefit, i.e. willingness to pay, is higher if somebody in the houshold fishes. Educated, young, urban, well-off citizens also put value on the non-use of the resource.
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| 22. |
- van Meel, Evelien R., et al.
(författare)
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Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children
- 2022
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Ingår i: European Respiratory Journal. - : EUROPEAN RESPIRATORY SOC JOURNALS LTD. - 0903-1936 .- 1399-3003. ; 60:4
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Tidskriftsartikel (refereegranskat)abstract
- Background Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. Methods We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. Results Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. Conclusions Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections.
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