| 1. |
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| 2. |
- Antonarakis, S. E., et al.
(författare)
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Factor VIII gene inversions in severe hemophilia A : Results of an international consortium study
- 1995
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 86:6, s. 2206-2212
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Tidskriftsartikel (refereegranskat)abstract
- Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells ware observed among 225 cases (≃ 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).
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| 3. |
- Clausen, Niels, et al.
(författare)
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Similar bleeding phenotype in young children with haemophilia A or B : A cohort study
- 2014
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 20:6, s. 747-755
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Tidskriftsartikel (refereegranskat)abstract
- The bleeding phenotype has been suggested to differ between haemophilia A and B. More knowledge on the bleeding phenotype at initiation of treatment is important to optimize patient care. The aim of this study was to investigate the severity of the bleeding phenotype and the variation in bleeding in children with severe or moderate haemophilia A and B. Consecutive, previously untreated patients with severe or moderate haemophilia A and B (factor VIII or IX activity <0.01 or 0.01-0.05 IU mL-1 respectively) born between January 1st 2000 and January 1st 2010 were included. Primary outcome was severity of bleeding tendency. Secondary outcome was variation in bleeding pattern. A total of 582 patients with severe haemophilia A and 76 with severe haemophilia B did not differ in age at first exposure to clotting factor (0.81 vs. 0.88 years, P = 0.20), age at first bleed (0.82 vs. 0.88 years, P = 0.36), and age at first joint bleed (1.18 vs. 1.20 years, P = 0.59). Patients with moderate haemophilia were older compared to patients with severe haemophilia. In patients with moderate haemophilia there were no clear differences between haemophilia A and B. Severity and variation in bleeding phenotype are similar during the early stage of treatment in patients with severe and moderate haemophilia A and B respectively. The findings imply that children with haemophilia B should be observed and treated as vigilantly as those with haemophilia A.
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| 4. |
- Halldén, Christer, 1957-, et al.
(författare)
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Investigation of disease-associated factors in haemophilia A patients without detectable mutations
- 2012
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Ingår i: Haemophilia. - : Blackwell. - 1351-8216 .- 1365-2516. ; 18:3, s. e132-e137
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Tidskriftsartikel (refereegranskat)abstract
- To investigate disease causing mechanism in haemophilia A patients without detectable mutation. Screening for F8 mutations in 307 haemophilia A patients using: re-sequencing and inversion PCR, reverse transcription (RT-PCR) of mRNA, MLPA analysis, haplotyping using SNP and microsatellite markers. No F8 mutations were detected in 9 of the 307 patients (2.9%) using re-sequencing and inversion PCR. MLPA analysis detected duplication in exon 6 in one patient and RT-PCR showed no products for different regions of mRNA in four other patients, indicating failed transcription. No obvious associations were observed between the phenotypes of the nine patients, their F8 haplotypes and the putative mutations detected. The mutation-positive patients carrying the same haplotypes as the mutation-negative patients show a multitude of different mutations, emphasizing the lack of associations at the haplotype level. VWF mutation screening and factor V measurements ruled out type 2N VWD and combined factor V and VIII deficiency respectively. To further investigate a possible role for FVIII interacting factors the haplotypes/diplotypes of F2, F9, F10 and VWF were compared. The nine patients had no specific haplotype/diplotype combination in common that can explain disease. Duplications and faulty transcription contribute to the mutational spectrum of haemophilia A patients where conventional mutation screening fail to identify mutations.
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| 5. |
- Hoots, W. K., et al.
(författare)
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Secondary prophylaxis with recombinant activated factor VII improves health-related quality of life of haemophilia patients with inhibitors
- 2008
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 14:3, s. 466-466
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Tidskriftsartikel (refereegranskat)abstract
- Haemophilia patients with inhibitors characteristically have impaired joint function and reduced health-related quality of life (HRQoL). This analysis examined whether secondary prophylaxis with recombinant activated factor VII (rFVIIa) improves HRQoL vs. conventional on-demand therapy in patients with haemophilia with inhibitors and frequent bleeds. After a 3-month preprophylaxis period, 22 patients received daily rFVIIa prophylaxis (90 or 270 mu g kg(-1)) for 3 months, followed by 3 months' postprophylaxis. Days of hospitalization, absence from school/work and mobility aids requirements were recorded. HRQoL was assessed by EuroQoL (EQ-5D) questionnaire, visual analogue scale (VAS), derived Time to Trade-Off (TTO) scores and Quality Adjusted Life Years (QALYs). rFVIIa prophylaxis significantly (P < 0.0001) reduced bleeding frequency vs. prior on-demand therapy. Hospitalization (5.9% vs. 13.5%; P = 0.0026) and absenteeism from school/work (16.7% vs. 38.7%; P = 0.0127) decreased during prophylaxis; these effects tended to be maintained during postprophylaxis. HRQoL (evaluated by EQ-5D) tended to improve during and after rFVIIa prophylaxis. Notably, pain decreased and mobility increased in 40.9% and 27.3% of patients, respectively, at the end of the postprophylaxis period vs. preprophylaxis. Median VAS score increased from 66 to 73 (P = 0.048), and TTO scores suggested better HRQoL (0.62 vs. 0.76; P = 0.054) during postprophylaxis than preprophylaxis. Small to moderate changes in effect sizes were reported for VAS and TTO scores. Median QALYs were 0.68 (VAS) and 0.73 (TTO). Reductions in bleeding frequency with secondary rFVIIa prophylaxis were associated with improved HRQoL vs. on-demand therapy.
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| 6. |
- Björck, Svante, et al.
(författare)
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A South Atlantic island record uncovers shifts in westerlies and hydroclimate during the last glacial
- 2019
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 15:6, s. 1939-1958
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Tidskriftsartikel (refereegranskat)abstract
- Changes in the latitudinal position and strength of the Southern Hemisphere westerlies (SHW) are thought to be tightly coupled to important climate processes, such as cross-equatorial heat fluxes, Atlantic Meridional Overturning Circulation (AMOC), the bipolar seesaw, Southern Ocean ventilation and atmospheric CO2 levels. However, many uncertainties regarding magnitude, direction, and causes and effects of past SHW shifts still exist due to lack of suitable sites and scarcity of information on SHW dynamics, especially from the last glacial. Here we present a detailed hydroclimate multiproxy record from a 36.4-18.6 kyr old lake sediment sequence on Nightingale Island (NI). It is strategically located at 37ĝF S in the central South Atlantic (SA) within the SHW belt and situated just north of the marine Subtropical Front (SF). This has enabled us to assess hydroclimate changes and their link to the regional climate development as well as to large-scale climate events in polar ice cores. The NI record exhibits a continuous impact of the SHW, recording shifts in both position and strength, and between 36 and 31 ka the westerlies show high latitudinal and strength-wise variability possibly linked to the bipolar seesaw. This was followed by 4 kyr of slightly falling temperatures, decreasing humidity and fairly southerly westerlies. After 27 ka temperatures decreased 3-4 ĝC, marking the largest hydroclimate change with drier conditions and a variable SHW position. We note that periods with more intense and southerly-positioned SHW seem to be related to periods of increased CO2 outgassing from the ocean, while changes in the cross-equatorial gradient during large northern temperature changes appear as the driving mechanism for the SHW shifts. Together with coeval shifts of the South Pacific westerlies, our results show that most of the Southern Hemisphere experienced simultaneous atmospheric circulation changes during the latter part of the last glacial. Finally we can conclude that multiproxy lake records from oceanic islands have the potential to record atmospheric variability coupled to large-scale climate shifts over vast oceanic areas..
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| 7. |
- Fuchs, I, et al.
(författare)
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Blue light regulates an auxin-induced K+-channel gene in the maize coleoptile
- 2003
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 100:20, s. 11795-11800
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Tidskriftsartikel (refereegranskat)abstract
- Auxin redistribution along gravistimulated maize coleoptiles causes differential expression of the auxin-induced K+-channel gene ZMK1 (Zea mays K+ channel 1) and precedes the curvature response. To evaluate the role of ZMK1 during phototropism, we here investigated blue light-stimulated coleoptiles. Four hours of blue light stimulation resulted in phototropic bending (23degrees). Rotation on a clinostat, at nominally "zero" gravity, and simultaneous stimulation with unidirectional blue light, however, resulted in up to 510 bending toward the light. Differential ZMK1 transcription reached a maximum after 90 min of blue light stimulation under gravity, whereas ZMK1 expression remained asymmetric for at least 180 min in photostimulated coleoptiles on a clinostat. We therefore conclude that the stronger phototropic bending under nominally "zero" gravity results from prolonged differential expression of ZMK1. Under both conditions, asymmetric expression of ZMK1 could be superimposed on the lateral auxin gradient across the coleoptile tip, whereas the gene for the blue light receptor phototropin 1 (PHOT1), expressed in the tip only, was not differentially regulated in response to blue light. The activation of the two different receptors eliciting the photo- and gravitropic response of the coleoptile thus feeds into a common signaling pathway, resulting in auxin redistribution in the coleoptile tip and finally in differential transcription of ZMK1. In the process of signal integration, gravity transduction restricts the magnitude of the blue light-inducible ZMK1 gradient. The spatial and temporal distribution of ZMK1 transcripts and thus differential K+ uptake in both flanks of the coleoptile seem to limit the stimulus-induced bending of this sensory organ.
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| 8. |
- Jernberg, T., et al.
(författare)
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Long-Term Effects of Oxygen Therapy on Death or Hospitalization for Heart Failure in Patients With Suspected Acute Myocardial Infarction
- 2018
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 138:24, s. 2754-2762
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the DETO2X-AMI trial (Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction), we compared supplemental oxygen with ambient air in normoxemic patients presenting with suspected myocardial infarction and found no significant survival benefit at 1 year. However, important secondary end points were not yet available. We now report the prespecified secondary end points cardiovascular death and the composite of all-cause death and hospitalization for heart failure. METHODS: In this pragmatic, registry-based randomized clinical trial, we used a nationwide quality registry for coronary care for trial procedures and evaluated end points through the Swedish population registry (mortality), the Swedish inpatient registry (heart failure), and cause of death registry (cardiovascular death). Patients with suspected acute myocardial infarction and oxygen saturation of >= 90% were randomly assigned to receive either supplemental oxygen at 6 L/min for 6 to 12 hours delivered by open face mask or ambient air. RESULTS: A total of 6629 patients were enrolled. Acute heart failure treatment, left ventricular systolic function assessed by echocardiography, and infarct size measured by high-sensitive cardiac troponin T were similar in the 2 groups during the hospitalization period. All-cause death or hospitalization for heart failure within 1 year after randomization occurred in 8.0% of patients assigned to oxygen and in 7.9% of patients assigned to ambient air (hazard ratio, 0.99; 95% CI, 0.84-1.18; P=0.92). During long-term follow-up (median [range], 2.1 [1.0-3.7] years), the composite end point occurred in 11.2% of patients assigned to oxygen and in 10.8% of patients assigned to ambient air (hazard ratio, 1.02; 95% CI, 0.88-1.17; P=0.84), and cardiovascular death occurred in 5.2% of patients assigned to oxygen and in 4.8% assigned to ambient air (hazard ratio, 1.07; 95% CI, 0.87-1.33; P=0.52). The results were consistent across all predefined subgroups. CONCLUSIONS: Routine use of supplemental oxygen in normoxemic patients with suspected myocardial infarction was not found to reduce the composite of all-cause mortality and hospitalization for heart failure, or cardiovascular death within 1 year or during long-term follow-up.
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| 9. |
- Kihlberg, K., et al.
(författare)
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Discrepancies between the one-stage clotting assay and the chromogenic assay in haemophilia B
- 2017
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 23:4, s. 620-627
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Assay discrepancy in factor VIII activity between the one-stage and the chromogenic assays has been described in approximately one third of patients with non-severe haemophilia A. Whether assay discrepancy may also occur in patients with haemophilia B remains unknown. Aim: This study compared the results from the one-stage and the chromogenic assays in patients with haemophilia B. Methods: Plasma samples from patients with haemophilia B attending the haemophilia centre in Malmö, Sweden, were collected after a wash-out period of more than 7 days and analysed with both assays. Results: Fifty samples from 36 patients were analysed. No discrepancy was found in patients with severe haemophilia B. Among the 44 plasma samples from patients with non-severe disease, 15 showed a twofold or greater difference between the results of the two methods, with the chromogenic method presenting the higher value (mean FIX:Cone-stage 0.02 vs. FIX:Cchromo 0.06 IU mL-1). Of these 15 samples, 14 were from seven individuals from five families with the same mutated amino acid at the N-terminal cleaving site of the activation peptide (FIX: c.572G>A; p.Arg191His or FIX: c.571C>T; p.Arg191Cys). These mutations were not observed in any patients with non-discrepant results. The reported bleeding frequency for these patients was low and indicative of a mild bleeding phenotype. Conclusion: Our findings imply that assay discrepancy occurs for factor IX activity and that both type of assays are needed for a correct diagnosis and classification of haemophilia B. The underlying mechanism by which the mutation influences the assays remains to be determined.
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| 10. |
- Nijdam, A., et al.
(författare)
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How to achieve full prophylaxis in young boys with severe haemophilia A: different regimens and their effect on early bleeding and venous access
- 2015
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 21:4, s. 444-450
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Tidskriftsartikel (refereegranskat)abstract
- To facilitate early prophylaxis, step-up regimens starting prophylaxis with infusions 1xweek(-1) were introduced. Choice of initial regimen may affect outcome. This study aims to classify initial prophylactic regimens and compare them on short-term outcome. From the European Paediatric Network for Haemophilia Management' (PedNet) registry, patients with severe haemophilia A without inhibitors, born 2000-2012, receiving prophylaxis were included. Treatment centres were classified according to the initial frequency of prophylactic infusions and the age at reaching infusions >= 3 x week(-1). Bleeding, and central venous access device (CVAD) use were compared at age 4 years. In 21 centres with 363 patients, three regimens were identified: (i) start prophylaxis with >= 3 x week(-1) infusions before age three (full: 19% of centres, 18% of patients); (ii) start 1-2 x week(-1), increasing frequency as soon as possible (asap), reaching >= 3 x week(-1) before age three (43% of centres, 36% of patients); (iii) start 1-2 x week(-1), increasing frequency according to bleeding (phenotype), reaching >= 3 x week(-1) after age three (38% of centres, 46% of patients). Prophylaxis was started at median 1.2 years on the full and asap regimen vs 1.8 years on the phenotype regimen. Complete prevention of joint bleeds was most effective on the full regimen (32% full vs. 27% asap and 8% phenotype), though at the cost of using most CVADs (88% full vs. 34% asap and 22% phenotype). The three prophylaxis regimens identified had different effects on early bleeding and CVAD use. This classification provides the first step towards establishing the optimum prophylactic regimen.
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| 11. |
- Peake, I R, et al.
(författare)
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Haemophilia : strategies for carrier detection and prenatal diagnosis
- 1993
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Ingår i: Bulletin of the World Health Organization. - 0042-9686. ; 71:3-4, s. 58-429
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Tidskriftsartikel (refereegranskat)abstract
- In 1977 WHO published in the Bulletin a Memorandum on Methods for the Detection of Haemophilia Carriers. This was produced following a WHO/WFH (World Federation of Haemophilia) Meeting of Investigators in Geneva in November 1976, and has served as a valuable reference article on the genetics of haemophilia. The analyses discussed were based on phenotypic assessment, which, at that time, was the only procedure available. The molecular biology revolution in genetics during the 1980s made enormous contributions to our understanding of the molecular basis of the haemophilias and now permits precise carrier detection and prenatal diagnosis. WHO and WFH held a joint meeting on this subject in February 1992 in Geneva. This article is the result of these discussions.
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| 12. |
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| 13. |
- Provan, SA, et al.
(författare)
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THE INCIDENCE OF INTERSTITIAL LUNG DISEASE IN PSORIATIC ARTHRITIS COMPARED TO RHEUMATOID ARTHRITIS. DATA FROM OVER 89 000 BDMARD TREATMENT COURSES DERIVED FROM FIVE NORDIC REGISTERS
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 133-134
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Interstitial lung disease (ILD) is an established extra-articular manifestation of rheumatoid arthritis (RA). Few studies have investigated the prevalence of ILD in patients with psoriatic arthritis (PsA). Methotrexate (MTX) is frequently used in the treatment of both RA and PsA and has been suggested to be a risk factor for the development of ILD. It is of interest to understand the interaction between disease and treatment in the development of ILD.Objectives:To compare the incidence of ILD between patient with PsA and RA treated with biologic disease modifying antirheumatic drugs (bDMARDS), with or without MTX as a co-medication.Methods:Cohorts of patients with RA and PsA starting bDMARD were identified in Nordic registers (Danish nationwide clinical register for patients with RA (DANBIO), Register on antirheumatic and biological therapy in Finland (ROB-FIN), Icelandic nationwide database of biologic therapy (ICEBIO), Norwegian Antirheumatic Drug Register (NOR-DMARD), and the Swedish Rheumatology Quality Register (SRQ)). Linkages to the National Patient Registers and to the Cause of Death Registers were performed in each country to identify cases of ILD. Each individual patient could contribute several treatment courses. ILD was identified as hospital or death certificate ICD10 codes of ILD (J84.1, J84.8, J84.9, J70.2, J70.3, J70.4, J99.0, J99.1, J99.8) given during the follow-up period which was defined as the treatment course duration, plus a 30-day wash-out period added to the end of treatment course period. MTX co-medication was specified as use of MTX at the start of bDMARD. Incidence rates (IR) for any ILD were calculated per 1000 person years at risk (PYR) for each country. The five cohorts were pooled and incidence rate ratios (IRR) for PsA vs. RA were calculated. Hazard ratios (HR) for any ILD in PsA vs. RA were estimated in Cox regression models adjusted for age, gender and repeated observations, and stratified for the use of MTX co-medication.Results:Overall 47 987 individual patients representing 89 239 bDMARD treatment courses and contributing 201 279 PYR were included in the study (Table 1). Methotrexate was reported as comedication in 29 916 (33.5 %) of the treatment courses (PsA vs. RA, 30.4 % vs 34.5 %). 970 cases of ILD were identified during the follow-up period. The risk of ILD was consistently lower in patients with PsA compared to patients with RA in all countries. In models stratified for co-medication the HR for ILD in PsA vs. RA was 0.34 (0.21-0.57) in patients treated with MTX and 0.26 (0.18-0.36) in patients not treated with MTX.Table 1.Interstitial lung disease in PsA vs. RA in five Nordic biologic registersDENMARKFINLANDICELANDNORWAYSWEDENRAPsARAPsARAPsARAPsARAPsANumber of individuals78293386494610916754701590999205966393Number of treatment courses17 07266408634184512808592379142738 27910 824Age baseline (SD)57.3 (13.1)49.0 (12.6)53.8 (13.4)48.8 (11.4)53.9 (14.2)50.1 (13.3)53.8 (13.7)48.7 (12.0)57.1 (13.7)50.6 (12.8)Female n (%)12 963 (76)3929 (59)6571 (76)933 (51)969 (76)551 (65)1815 (77)818 (57)29 635 (77)6162 (57)Number of PYR4023513986217984910451727994556265312033427412ILD-events within PYR2182213287232668028IR pr 1000 PYR5.41.66.11.61.50.77.02.35.71.0IRR PsA vs RA crude0.29 (0.18-0.45)0.27 (0.11-0.55)0.46 (0.05-2.42)0.32(0.11-0.78)0.18 (0.12-0.26)HR PsA vs RA0.31 (0.17-0.56)0.46 (0.22-0.96)0.62 (0.12-3.14)0.19 (0.06-0.54)0.25 (0.17-0.37)PYR: Patient years at risk, IR: Incidence rates, IRR: Incidence rate ratios, HR: Hazard RatiosConclusion:In these preliminary analyses, the incidence of ILD is lower in bDMARD treated PsA vs. RA patients, irrespective of co-medication with MTX. This indicates that the clinician should consider the rheumatological diagnosis when assessing the risk for future ILD in patients treated with bDMARDs and MTX.Acknowledgements:Partly funded by NordForsk and FOREUMDisclosure of Interests:Sella Aarrestad Provan Consultant of: Novartis, Grant/research support from: Boehringer-Ingelheim, Brigitte Michelsen: None declared, Lotta Ljung: None declared, Thorarinn Jonmundsson: None declared, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, Daniela Di Giuseppe: None declared, Merete Lund Hetland Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis, Consultant of: Eli Lilly, Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Guðrún Björk Reynisdóttir: None declared, Bente Glintborg: None declared, Eirik kristianslund: None declared, Heikki Relas: None declared, Kalle Aaltonen: None declared, Dan Nordström Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, MSD, Novartis, Pfizer, Roche and UCB., Consultant of: Abbvie, BMS, Celgene, Eli Lilly, MSD, Novartis, Pfizer, Roche and UCB., Tore K. Kvien Speakers bureau: Amgen, Celltrion, Egis, Evapharma, Ewopharma, Hikma, Oktal, Sandoz, Sanofi., Consultant of: AbbVie, Amgren, Biogen, Celltrion, Eli Lilly, Gilead, Mylan, Novartis, Pfizer, Roche, Sandoz, Sanofi., Johan Askling Grant/research support from: Abbvie, BMS, Eli Lilly, Merck, Pfizer, Roche, Samsung Bioepis, and Sanofi
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| 14. |
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| 15. |
- Andersson, B, et al.
(författare)
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Ökad fysisk aktivitet viktigt för att bromsa sjukfrånvaron
- 2015
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Ingår i: Dagens nyheter, DN.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Försäkringskassans rapport (DN Debatt 27/11 2015) visar att sjukfrånvaron fortsätter att öka och lovar att kraftsamla i sjukförsäkringshandläggningen. Men, precis som Försäkringskassan skriver, kommer det inte att räcka för att nå regeringens mål. Regeringens åtgärdsprograms program i sju punkter för att minska sjukfrånvaron saknar en viktig komponent. Det måste kompletteras med fysisk aktivitet som ett åttonde område för att trenden ska kunna brytas, skriver 13 debattörer.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Barlier, I, et al.
(författare)
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The SUR2 gene of Arabidopsis thaliana encodes the cytochrome P450 CYP83B1, a modulator of auxin homeostasis.
- 2000
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 97:26
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Tidskriftsartikel (refereegranskat)abstract
- Genetic screens have been performed to identify mutants with altered auxin homeostasis in Arabidopsis. A tagged allele of the auxin-overproducing mutant sur2 was identified within a transposon mutagenized population. The SUR2 gene was cloned and shown to encode the CYP83B1 protein, which belongs to the large family of the P450-dependent monooxygenases. SUR2 expression is up-regulated in sur1 mutants and induced by exogenous auxin in the wild type. Analysis of indole-3-acetic acid (IAA) synthesis and metabolism in sur2 plants indicates that the mutation causes a conditional increase in the pool size of IAA through up-regulation of IAA synthesis.
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| 23. |
- Berntorp, Erik, et al.
(författare)
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Consensus perspectives on prophylactic therapy for haemophilia: summary statement.
- 2003
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 9:Suppl 1, s. 41278-41278
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Tidskriftsartikel (refereegranskat)abstract
- Participants in an international conference on prophylactic therapy for severe haemophilia developed a consensus summary of the findings and conclusions of the conference. In the consensus, participants agreed upon revised definitions for primary and secondary prophylaxis and also made recommendations concerning the need for an international system of pharmacovigilance. Considerations on starting prophylaxis, monitoring outcomes, and individualizing treatment regimens were discussed. Several research questions were identified as needing further investigation, including when to start and when to stop prophylaxis, optimal dosing and dose interval, and methods for assessment of long-term treatment effects. Such studies should include carefully defined cohorts, validated orthopaedic and quality-of-life assessment instruments, and cost-benefit analyses.
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| 24. |
- Bienert, K., et al.
(författare)
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The biomethane map - Research coordination for a low-cost biomethane production at small and medium scale applications
- 2017
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Ingår i: European Biomass Conf. Exhib. Proc.. - : ETA-Florence Renewable Energies. ; , s. 1097-1104
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Konferensbidrag (refereegranskat)abstract
- The European Horizon 2020 project “Research Coordination for a Low-Cost Biomethane Production at Small and Medium Scale Applications”, short Record Biomap, aims to build up a knowledge transfer platform to foster the use of research outcomes which are often insufficiently exploited after the end of a research project. In the focus are technology solutions for a cost efficient biomethane production at small to medium scale, which is not yet economically competitive compared to large scale applications. Technology developments along the biomethane supply chain, from substrate pre-treatment, digestion systems up to gas upgrading processes, especially for those technologies which are yet in the first phases of their development are monitored and supported during the project duration. The present paper will give an overview of the project´s focus. The current status of collected technology profiles is presented. The promising innovative technologies “ultra-sound and hydrodynamic cavitation” for substrate pre-treatment, the “high organic loading plug-flow digestion system” and the “in-situ methane enrichment in combination with a wood ash filter” to upgrade the biogas to biomethane are explained in detail. Furthermore, the first findings on R&D needs and framework conditions are highlighted. © 2017, ETA-Florence Renewable Energies. All rights reserved.
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| 25. |
- Brink, M, et al.
(författare)
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PULMONARY FIBROSIS IN EARLY RHEUMATOID ARTHRITIS IN RELATION TO GENETIC LOCI AND INDIVIDUAL ACPA SPECIFICITIES
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 203-204
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Pulmonary manifestations in rheumatoid arthritis (RA) are common comorbidities but the underlying mechanisms are largely unknown. We found in a previous study 3 SNPs associated with pulmonary fibrosis (PF); rs35705950 (MUC5B), rs111521887 (TOLLIP), and rs2609255 (FAM13A) besides age, rheumatoid factor positivity and methotrexate treatment.ObjectivesTo evaluate for the added value of a multiplex of anti-citrullinated peptide antibodies (ACPA) for the development of pulmonary fibrosis (PF) in an inception cohort of RA patients.MethodsA total of 1184 patients with early RA were consecutively included and followed prospectively from the date of diagnosis (index date) until death or until 31 December 2016. The diagnosis of PF was based on high resolution tomography. The presence of 21 ACPA fine specificities were analysed in plasma sampled at index date, using a custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden). Data on both ACPA and genetic data was available for 841 RA patients, of whom 50 developed PF. Associations were analysed using logistic regression analysis and presented as the odds ratio (OR) with the 95% confidence interval (CI). Models were adjusted for sex, age, DAS28 and presence of RF at RA diagnosis, smoking ever, and HLA-SE and in a second step for the three SNPs (.rs35705950, rs111521887 and rs2609255), respectively.ResultsIn unadjusted analyses eight ACPA reactivities were found associated with PF development (p< 0.05-0.001). The number of ACPA reactivities was related to PF development, both in crude and adjusted models (p<0.05 for both). In models concomitantly adjusted for the three SNPs (rs35705950, rs111521887 and rs2609255) respectively, in addition to mentioned adjustments the number of ACPA reactivities (p<0.05 for all three nmodels), Vim60-75 (p<0.05, in all three models), Fibβ62–78 (72) (p<0.001-p<0.05) and F4-CIT-R (p<0.01-p<0.05) were all found significantly associated to PF development irrespective of the SNPs.ConclusionThe development of PF in an inception cohort of RA patients was associated both with risk genes and, independently of the risk genes, the presence of certain ACPA, and the number of ACPA reactivities.References[1]Jönsson E, et al. Pulmonary fibrosis in relation to genetic loci in an inception cohort of patients with early rheumatoid arthritis from northern Sweden. Rheumatology (Oxford). 2021 May 16:keab441. doi: 10.1093/rheumatology/keab441.AcknowledgementsI have no acknowledgements to declare. The staff and patients at the departments of rheumatology in northern Sweden.Disclosure of InterestsNone declared
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| 26. |
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| 27. |
- Charrieau, Laurie M., et al.
(författare)
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The effects of multiple stressors on the distribution of coastal benthic foraminifera: A case study from the Skagerrak-Baltic Sea region
- 2018
-
Ingår i: Marine Micropaleontology. - : Elsevier BV. - 0377-8398. ; 139, s. 42-56
-
Tidskriftsartikel (refereegranskat)abstract
- Coastal ecosystems are subjected to both large natural variability and increasing anthropogenic impact on environmental parameters such as changes in salinity, temperature, and pH. This study documents the distribution of living benthic foraminifera under the influence of multiple environmental stressors in the Skagerrak-Baltic Sea region. Sediment core tops were studied at five sites along a transect from the Skagerrak to the Baltic Sea, with strong environmental gradients, especially in terms of salinity, pH, calcium carbonate saturation and dissolved oxygen concentration in the bottom water and pore water. We found that living foraminiferal densities and species richness were higher at the Skagerrak station, where the general living conditions were relatively beneficial for Foraminifera, with higher salinity and Ωcalc in the water column and higher pH and oxygen concentration in the bottom and pore water. The most common species reported at each station reflect the differences in the environmental conditions between the stations. The dominant species were Cassidulina laevigata and Hyalinea balthica in the Skagerrak, Stainforthia fusiformis, Nonionella aff. stella and Nonionoides turgida in the Kattegat and N. aff. stella and Nonionellina labradorica in the Öresund. The most adverse conditions, such as low salinity, low Ωcalc, low dissolved oxygen concentrations and low pH, were noted at the Baltic Sea stations, where the calcareous tests of the dominant living taxa Ammonia spp. and Elphidium spp. were partially to completely dissolved, probably due to a combination of different stressors affecting the required energy for biomineralization. Even though Foraminifera are able to live in extremely varying environmental conditions, the present results suggest that the benthic coastal ecosystems in the studied region, which are apparently affected by an increase in the range of environmental variability, will probably be even more influenced by a future increase in anthropogenic impacts, including coastal ocean acidification and deoxygenation.
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| 28. |
- Delcoigne, Bénédicte, et al.
(författare)
-
How does current disease activity in rheumatoid arthritis affect the short-term risk of acute coronary syndrome? : A clinical register based study from Sweden and Norway
- 2023
-
Ingår i: European journal of internal medicine. - 0953-6205 .- 1879-0828. ; 115, s. 55-61
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To estimate short-term risks of acute coronary syndrome (ACS) in patients with rheumatoid arthritis (RA) as a function of current RA disease activity including remission.Methods: Data from clinical visits of RA patients in Sweden (SE) and Norway (NO) between January 1st 2012 until December 31st 2020 were used. At each visit, patient's disease activity was assessed including remission status (measured with several metrics). Through linkage to national health and death registers, patients were followed up for incident ACS up to six months from each visit. We compared the short-term risk of ACS in patients not in remission vs. in remission using Cox regression analyses with robust standard errors, adjusted for country and covariates (e.g., age, sex, prednisolone use, comorbidities). We also explored disease activity categories as exposure.Results: We included 212,493 visits (10,444 from Norway and 202,049 from Sweden) among 41,250 patients (72% women, mean age at visit 62 years). During the 6-month follow-ups, we observed 524 incident ACS events. Compared to patients in remission, patients currently not in remission had an increased rate of ACS: adjusted hazard ratio (95% confidence interval) 1.52 (1.24–1.85) with DAS28 metric. The crude absolute six-month risks were 0.2% for patients in remission vs. 0.4% for patients with DAS28 high disease activity. The use of alternative RA disease activity and remission metrics provided similar results.Conclusion: Failure to reach remission is associated with elevated short-term risks of ACS, underscoring the need for CV risk factor optimization in these patients.
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| 29. |
- Delcoigne, B., et al.
(författare)
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SHORT- AND LONGER-TERM RISKS FOR ACUTE CORONARY SYNDROME IN PATIENTS WITH RHEUMATOID ARTHRITIS STARTING TREATMENT WITH DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS : A COLLABORATIVE OBSERVATIONAL HEAD-TO-HEAD STUDY ACROSS FIVE NORDIC RHEUMATOLOGY REGISTERS
- 2021
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80, s. 63-64
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Rheumatoid Arthritis (RA) is associated with increased cardiovascular co-morbidity including acute coronary syndrome (ACS), partly due to effects of systemic inflammation. Disease-modifying anti-rheumatic drugs (DMARDs) may reduce RA disease activity, but act through several pathways and may themselves have an impact on cardiovascular risks. Whether the risks of ACS associated with biologic (b) and targeted synthetic (ts) DMARDs differ is still unknown.Objectives:To assess and compare incidences of ACS during treatment of RA with etanercept (ETA), adalimumab (ADA), infliximab (INF), certolizumab pegol (CTZ), golimumab (GOL), rituximab (RIT), abatacept (ABA), tocilizumab (TCZ), baricitinib (BAR) or tofacitinib (TOF).Methods:We defined and pooled treatment cohorts of patients starting any of the above treatments between 2008 and 2017 from clinical rheumatology registers in Denmark (DK), Finland (FI), Norway (NO), and Sweden (SE). One patient could contribute several treatment episodes. Age, sex, co-medication (methotrexate, prednisolone), number of previous b/tsDMARDs, CRP, comorbidities (cardiovascular (including ACS (defined as ICD-10: I20.0, I21.0-4, I21.9) and cerebrovascular disease, thromboembolic events, diabetes, hospitalized infection, cancer, kidney failure, COPD) and associated drugs were extracted and used as adjustment in Cox regression analyses comparing the incidence of ACS between treatments. We used several follow-up lengths (1, 2, and up to 5 years) and two different risk windows (ACS on drug [ending follow-up on treatment discontinuation] and ACS ever since treatment start [disregarding any treatment discontinuation]). We also stratified by age and number of previous b/tsDMARDs.Results:We included 40850 treatment courses in 24083 patients (DK 7271, FI 3732, NO 1540, and SE 11540; around 75% women). ETA was the most common treatment (27%) whereas BAR and TOF comprised <1%, and the other DMARDs 6-14% each. The proportions with a history of ACS at treatment start ranged from 1.2% (NO) to 1.8% (DK).We found 780 incident ACS events during 141 326 person-years (pyrs) in the 5-year follow-up time and “ACS ever since treatment start” risk window, resulting in a crude incidence rate of 5.5 events per 1000 pyrs. No event was recorded for BAR nor TOF, which also had the shortest follow-up. Adjusted hazard ratios (HR) increased slightly with longer follow-up times, but the two risk windows provided similar HRs. For the 5-year follow-up, RIT was associated with an increased risk of ACS compared to ETA (Table), while no association was observed for shorter follow-up times. Stratifying on age did not modify the associations. Separate analyses by number of previous b/tsDMARDs suggested that ABA (HR=1.8, 95% CI 1.0-3.3), INF (HR=2.2, 95% CI 1.0-4.6) and RIT (HR=1.9, 95% CI 1.1-3.4) were associated with increased risks of ACS compared to ETA in the subgroup of patients with two or more previous bDMARDs (Figure), whereas no differences were found among patients starting either drug as 1st/2nd bDMARD.Table 1.Comparisons of risks for ACS during a 5-year follow-up since start of bDMARD treatment.DrugN eventspyrsCrude incidence rate/ 1000 pyrsHR (95% CI)1ETA175359174.9ref.ADA115240934.81.0 (0.8-1.3)CTZ54141583.80.9 (0.6-1.2)GOL4090064.41.1 (0.8-1.5)INF106178036.01.2 (0.9-1.5)ABA70107956.51.1 (0.8-1.4)RIT158166229.51.3 (1.0-1.6)TCZ62128664.80.9 (0.5-1.2)BAR036TOF030Pyrs: person-years; HR: hazards ratio1 adjustment: see text.Conclusion:In this cohort including ≥ 24,000 patients followed for up to 5 years, the ACS incidence rate was 5.5/1000 pyrs, with RIT showing an increased risk compared to ETA. In clinical practice, the choice of bDMARD does not seem to influence ACS risk in the short term. In the longer term, differences in ACS risk between bDMARDs may reflect channeling to these, or truly differential effects in subpopulations of patients.Acknowledgements:Partly funded by Nordforsk and ForeumDisclosure of Interests:Bénédicte Delcoigne: None declared, Lotta Ljung: None declared, Sella Aa. Provan Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Boehringer- Ingelheim, Bente Glintborg Grant/research support from: Pfizer, BMS, AbbVie, Kathrine Lederballe Gron Grant/research support from: BMS, Merete L. Hetland Consultant of: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Grant/research support from: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Niels Steen Krogh: None declared, Nina Trokovic: None declared, Heikki Relas Speakers bureau: Abbvie, Celgene, Pfizer, Grant/research support from: Abbvie, Celgene, Pfizer, Carl Turesson Speakers bureau: Abbvie, Bristol-Myers Squibb, Medac, Pfizer, Roche, Consultant of: Roche, Brigitte Michelsen Consultant of: Novartis (paid to employer), Grant/research support from: Novartis (paid to employer), Johan Askling Consultant of: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB. These entities have entered into agreements with Karolinska Institutet with JA as principal investigator, mainly in the context of safety monitoring of biologics via the ARTIS national safety monitoring system.
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| 30. |
- Dieckmann, Mark E, 1969-, et al.
(författare)
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Three-dimensional visualization of electron acceleration in a magnetized plasma
- 2002
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Ingår i: IEEE Transactions on Plasma Science. - 0093-3813 .- 1939-9375. ; 30:1 I, s. 20-21
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Tidskriftsartikel (refereegranskat)abstract
- We examine wave-particle interactions in a magnetized plasma. We present snapshots of an animation of the three-dimensional electron phase space distribution produced by an electrostatic wave propagating across a magnetic field. The distribution function has been evolved by a particle in cell simulation. The electron phase space has been visualized by distributing the simulation electrons over an array representing phase space density and by volume rendering this array. The results are, due to the choice of initial plasma and wave parameters, of relevance for electron acceleration at astrophysical shocks.
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| 31. |
- Dong, Yang, et al.
(författare)
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HEARTBREAK Controls Post-translational Modification of INDEHISCENT to Regulate Fruit Morphology in Capsella
- 2020
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 30:19, s. 3880-3888
-
Tidskriftsartikel (refereegranskat)abstract
- Morphological variation is the basis of natural diversity and adaptation. For example, angiosperms (flowering plants) evolved during the Cretaceous period more than 100 mya and quickly colonized terrestrial habitats [1]. A major reason for their astonishing success was the formation of fruits, which exist in a myriad of different shapes and sizes [2]. Evolution of organ shape is fueled by variation in expression patterns of regulatory genes causing changes in anisotropic cell expansion and division patterns [3-5]. However, the molecular mechanisms that alter the polarity of growth to generate novel shapes are largely unknown. The heart-shaped fruits produced by members of the Capsella genus comprise an anatomical novelty, making it particularly well suited for studies on morphological diversification [6-8]. Here, we show that post-translational modification of regulatory proteins provides a critical step in organ-shape formation. Our data reveal that the SUMO protease, HEARTBREAK (HTB), from Capsella rubella controls the activity of the key regulator of fruit development, INDEHISCENT (CrIND in C. rubella), via de-SUMOylation. This post-translational modification initiates a transduction pathway required to ensure precisely localized auxin biosynthesis, thereby facilitating anisotropic cell expansion to ultimately form the heart-shaped Capsella fruit. Therefore, although variation in the expression of key regulatory genes is known to be a primary driver in morphological evolution, our work demonstrates how other processes-such as post-translational modification of one such regulator-affects organ morphology.
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| 32. |
- Fagerlind, Helen, 1975, et al.
(författare)
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Development of an In-depth European Accident Causation Database and the Driving Reliability and Error Analysis Method, DREAM 3.0
- 2008
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Ingår i: 3rd International Conference ESAR (Expert Symposium on Accident Research). - Hannover, Tyskland.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The SafetyNet project was formulated in part to address the need for safety oriented European road accident data. One of the main tasks included within the project was the development of a methodology for better understanding of accident causation together with the development of an associated database involving data obtained from on-scene or “nearly on-scene” accident investigations. Information from these investigations was complemented by data from follow-up interviews with crash participants to determine critical events and contributory factors to the accident occurrence. A method for classification of accident contributing factors, known as DREAM 3.0, was developed and tested in conjunction with the SafetyNet activities. Collection of data and case analysis for some 1 000 individual crashes have recently been completed and inserted into the database and therefore aggregation analyses of the data are now being undertaken. This paper describes the methodology development, an overview of the database and the initial aggregation analyses.
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| 33. |
- Falck, Tillmann, et al.
(författare)
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Segmentation of Time Series from Nonlinear Dynamical Systems
- 2011
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Ingår i: Proceedings of the 18th IFAC World Congress. - 9783902661937 ; , s. 13209-13214
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Konferensbidrag (refereegranskat)abstract
- Segmentation of time series data is of interest in many applications, as for example in change detection and fault detection. In the area of convex optimization, the sum-of-norms regularization has recently proven useful for segmentation. Proposed formulations handle linear models, like ARX models, but cannot handle nonlinear models. To handle nonlinear dynamics, we propose integrating the sum-of-norms regularization with a least squares support vector machine (LS-SVM) core model. The proposed formulation takes the form of a convex optimization problem with the regularization constant trading off the fit and the number of segments.
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| 34. |
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| 35. |
- Fischer, K, et al.
(författare)
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Prophylactic treatment for severe haemophilia: comparison of an intermediate-dose to a high-dose regimen
- 2002
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 8:6, s. 753-760
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Tidskriftsartikel (refereegranskat)abstract
- A multicentre study was performed in Sweden and the Netherlands, comparing effects of two prophylactic regimens in 128 patients with severe haemophilia, born 1970-90. 42 Swedish patients (high-dose prophylaxis), were compared with 86 Dutch patients (intermediate-dose prophylaxis). Patients were evaluated at the date of their last radiological score according to Pettersson. Annual clotting factor consumption and bleeding frequency were registered for a period of three years before evaluation. Patients in the high-dose group were younger at evaluation (median 15.2 vs. 17.9 years), started prophylaxis earlier (median 2 vs. 5 years), and used 2.19 times more clotting factor kg(-1) year(-1). Patients treated with high-dose prophylaxis had fewer joint bleeds (median 0.3 year(-1) vs. 3.3 year(-1)) and the proportion of patients without arthropathy as measured by the Pettersson score was higher (69% vs. 32%), however, the age-adjusted difference in scores (median 0 points vs. 4 points) was small and at present not statistically significant. Clinical scores and quality of life were similar. These findings suggest that, compared with intermediate-dose prophylaxis, high-dose prophylaxis significantly increases treatment costs and reduces joint bleeds over a period of 3 years, but only slightly reduces arthropathy after 17 years of follow-up.
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| 36. |
- Fischer, K, et al.
(författare)
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Prophylaxis for severe haemophilia: clinical challenges in the absence as well as in the presence of inhibitors
- 2008
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 14:s3, s. 196-201
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Tidskriftsartikel (refereegranskat)abstract
- Prophylaxis is defined as the regular administration of clotting factor concentrates to prevent bleeding. Extensive data from observational studies and a recent randomized controlled trial (have established that early prophylactic treatment prevents bleeds and arthropathy in boys with severe haemophilia. The initiation of prophylaxis in young children remains challenging. To prevent arthropathy, prophylaxis should be started early, before the onset of joint damage. Alternative strategies of starting include starting before the age of 2 years, or starting before the third joint bleed. Dose and frequency vary between the original Swedish regime of 20-40 IU kg(-1) three times per week and lower dosed and step up regimes starting with 50 IU kg(-1) once weekly and rapidly increasing dose and frequency in case of bleeds. In the second decade, most patients on prophylaxis learn self-infusion. Self-management warrants confirmation of adequate knowledge of the disease. Increasing self-management concurring with major physical and psychological changes may cause reduced adherence. The challenge is to promote adherence and continue to prevent bleeds during this important period of rapid growth. The third decade of life often represents a change in lifestyle. Patients may get a job and periods of physical activity may be more confined. About two thirds of patients experiment with discontinuing prophylaxis in their early twenties, and 20-30% with mild bleeding patterns switch to on-demand treatment for prolonged periods or even permanently. The challenge is to optimize efficiency by individualizing prophylactic dose and frequency according to lifestyle and bleeding pattern. Inhibitors may develop in up to 30% of patients with severe haemophilia. Especially those with high titre inhibitors are at increased risk of developing target joints and severe arthropathy. The use of prophylactic treatment with bypassing agents in inhibitor patients is increasing. Early studies report in a significant reduction of bleeds, including intracranial bleeds, and improvement in quality of life. Data on results of primary prophylaxis in patients with inhibitors to prevent arthropathy are not yet available.
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| 37. |
- Fischer, K., et al.
(författare)
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Prospective observational cohort studies for studying rare diseases: the European PedNet Haemophilia Registry
- 2014
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 20:4, s. 280-286
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Tidskriftsartikel (refereegranskat)abstract
- Haemophilia is a rare disease. To improve knowledge, prospective studies of large numbers of subjects are needed. To establish a large well-documented birth cohort of patients with haemophilia enabling studies on early presentation, side effects and outcome of treatment. Twenty-one haemophilia treatment centres have been collecting data on all children with haemophilia with FVIII/IX levels up to 25% born from 2000 onwards. Another eight centres collected data on severe haemophilia A only. At baseline, details on delivery and diagnosis, gene mutation, family history of haemophilia and inhibitors are collected. For the first 75 exposure days, date, reason, dose and product are recorded for each infusion. Clinically relevant inhibitors are defined as follows: at least two positive inhibitor titres and a FVIII/IX recovery <66% of expected. For inhibitor patients, results of all inhibitor- and recovery tests are collected. For continued treatment, data on bleeding, surgery, prophylaxis and clotting factor consumption are collected annually. Data are downloaded for analysis annually. In May 2013, a total of 1094 patients were included: 701 with severe, 146 with moderate and 247 with mild haemophilia. Gene defect data were available for 87.6% of patients with severe haemophilia A. The first analysis, performed in May 2011, lead to two landmark publications. The outcome of this large collaborative research confirms its value for the improvement of haemophilia care. High-quality prospective observational cohorts form an ideal source to study natural history and treatment in rare diseases such as haemophilia.
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| 38. |
- Forsblad-d'Elia, H, et al.
(författare)
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Biomechanical Properties of Common Carotid Arteries Assessed by Circumferential 2D Strain and β Stiffness Index in Patients With Ankylosing Spondylitis
- 2021
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Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 48:3, s. 352-360
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Tidskriftsartikel (refereegranskat)abstract
- Ankylosing spondylitis (AS) is associated with an elevated risk of cardiovascular disease (CVD) related to atherosclerosis, preceded by arterial stiffness. We aimed to examine common carotid artery (CCA) biomechanical properties using ultrasound to calculate β stiffness index (indicating arterial stiffness) and, a more recently developed technique, 2-dimensional (2D) speckle tracking strain (indicating arterial motion and deformation, strain) to (1) compare with age- and sex-matched controls, and (2) analyze relationships between strain and stiffness with disease characteristics and traditional risk factors for CVD in patients with AS.Methods.In this cross-sectional study, a cohort of 149 patients with AS, mean age 55.3 ± 11.2 years, 102 (68.5%) men, and 146 (98%) HLA-B27–positive, were examined. Bilateral CCA were examined for circumferential 2D strain and β stiffness index. A subgroup of 46 patients was compared with 46 age- and sex-matched controls, both groups without hypertensive disease, diabetes, myocardial infarction, or stroke.Results.Mean bilateral circumferential 2D strain was lower in AS patients compared with controls (7.9 ± 2.6% vs 10.3 ± 1.9%, P < 0.001), whereas mean bilateral β stiffness index was higher (13.1 ± 1.7 mmHg/mm vs 12.3 ± 1.3 mmHg/mm, P = 0.02). In multivariable linear regression analyses, strain was associated with age, erythrocyte sedimentation rate, history of anterior uveitis, and treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARD) and/or biological DMARD (R2 0.33), while stiffness was associated with age (R2 0.19).Conclusion.Both CCA circumferential 2D strain and β stiffness index differed between patients with AS and controls. Strain was associated with AS-related factors and age, whereas only age was associated with stiffness, suggesting that the obtained results reflect different pathogenic vascular processes.
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| 39. |
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| 40. |
- Graham, J B, et al.
(författare)
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Carrier detection in hemophilia A : a cooperative international study. I. The carrier phenotype
- 1986
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Ingår i: Blood. - 0006-4971. ; 67:6, s. 9-1554
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Tidskriftsartikel (refereegranskat)abstract
- Eight laboratories in six countries cooperated to clarify several issues concerning the phenotypes of heterozygous carriers of hemophilia "A." Plasma levels of factor VIII (F.VIII:C, formerly VIII:C) and von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) of carriers and normal women were determined by various "in-house" methods; a single lyophilized plasma standard was used for all assays. Analysis of the collated data from 336 carriers (296 obligatory carriers and 40 sporadic carriers) and 137 normal women showed that there was no difference in the F.VIII:C levels of "paternal" carriers (women who had obtained the abnormal gene from their fathers) and "maternal" carriers. Neither was there a difference in the VWF:Ag levels of normal women and either type of carrier. Age was found to have a significant effect on both F.VIII:C and VWF:Ag, values being higher at very young and very old ages, the minima occurring in the 25- to 30-year range. ABO blood type had a striking effect. Women of types A, B, and AB (designated non-O in the study), both normals and carriers, had significantly higher levels of both factors than did women of type O. Analysis by laboratories showed that differences in mean levels of both factors between laboratories were highly significant. It was concluded that age, ABO blood type, and laboratory variation should be taken into account in carrier detection.
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| 41. |
- Green, P P, et al.
(författare)
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Carrier detection in hemophilia A : a cooperative international study. II. The efficacy of a universal discriminant
- 1986
-
Ingår i: Blood. - 0006-4971. ; 67:6, s. 7-1560
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Tidskriftsartikel (refereegranskat)abstract
- Factor VIII (F.VIII) and von Willebrand factor (VWF):Ag data collected by eight laboratories on a total of 336 obligatory carriers of hemophilia A and 137 normal women were used to answer several questions concerning the construction of linear discriminants for carrier detection. It was found: that a "universal" linear discriminant can be constructed which is suitable for use in all laboratories and is nearly as effective as laboratory-specific discriminants; that inclusion of age and ABO blood type data improved the efficacy of these discriminants; that substitution of alternative assays for F.VIII and VWF:Ag did not generally improve the efficacy of the discriminants over that obtained using the bioassay for F.VIII:C and Laurell's immunoassay for VWF:Ag; that linear discriminants were far more effective than discriminants based on the F.VIII:C/VWF:Ag ratio. A step-wise procedure is given which any laboratory may follow in using the universal discriminant for carrier detection.
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| 42. |
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| 43. |
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| 44. |
- Janszky, I, et al.
(författare)
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Chocolate consumption and mortality following a first acute myocardial infarction : the Stockholm Heart Epidemiology Program
- 2009
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 266:3, s. 248-257
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVESTo assess the long-term effects of chocolate consumption amongst patients with established coronary heart disease.DESIGNIn a population-based inception cohort study, we followed 1169 non-diabetic patients hospitalized with a confirmed first acute myocardial infarction (AMI) between 1992 and 1994 in Stockholm County, Sweden, as part of the Stockholm Heart Epidemiology Program. Participants self-reported usual chocolate consumption over the preceding 12 months with a standardized questionnaire distributed during hospitalization and underwent a health examination 3 months after discharge. Participants were followed for hospitalizations and mortality with national registries for 8 years.RESULTSChocolate consumption had a strong inverse association with cardiac mortality. When compared with those never eating chocolate, the multivariable-adjusted hazard ratios were 0.73 (95% confidence interval, 0.41-1.31), 0.56 (0.32-0.99) and 0.34 (0.17-0.70) for those consuming chocolate less than once per month, up to once per week and twice or more per week respectively. Chocolate consumption generally had an inverse but weak association with total mortality and nonfatal outcomes. In contrast, intake of other sweets was not associated with cardiac or total mortality.CONCLUSIONSChocolate consumption was associated with lower cardiac mortality in a dose dependent manner in patients free of diabetes surviving their first AMI. Although our findings support increasing evidence that chocolate is a rich source of beneficial bioactive compounds, confirmation of this strong inverse relationship from other observational studies or large-scale, long-term, controlled randomized trials is needed.
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| 45. |
- Jernberg, Tomas, et al.
(författare)
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Long-Term Effects of Oxygen Therapy on Death or Hospitalization for Heart Failure in Patients With Suspected Acute Myocardial Infarction
- 2018
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 138:24, s. 2754-2762
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the DETO2X-AMI trial (Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction), we compared supplemental oxygen with ambient air in normoxemic patients presenting with suspected myocardial infarction and found no significant survival benefit at 1 year. However, important secondary end points were not yet available. We now report the prespecified secondary end points cardiovascular death and the composite of all-cause death and hospitalization for heart failure.Methods: In this pragmatic, registry-based randomized clinical trial, we used a nationwide quality registry for coronary care for trial procedures and evaluated end points through the Swedish population registry (mortality), the Swedish inpatient registry (heart failure), and cause of death registry (cardiovascular death). Patients with suspected acute myocardial infarction and oxygen saturation of ≥90% were randomly assigned to receive either supplemental oxygen at 6 L/min for 6 to 12 hours delivered by open face mask or ambient air.Results: A total of 6629 patients were enrolled. Acute heart failure treatment, left ventricular systolic function assessed by echocardiography, and infarct size measured by high-sensitive cardiac troponin T were similar in the 2 groups during the hospitalization period. All-cause death or hospitalization for heart failure within 1 year after randomization occurred in 8.0% of patients assigned to oxygen and in 7.9% of patients assigned to ambient air (hazard ratio, 0.99; 95% CI, 0.84–1.18; P=0.92). During long-term follow-up (median [range], 2.1 [1.0–3.7] years), the composite end point occurred in 11.2% of patients assigned to oxygen and in 10.8% of patients assigned to ambient air (hazard ratio, 1.02; 95% CI, 0.88–1.17; P=0.84), and cardiovascular death occurred in 5.2% of patients assigned to oxygen and in 4.8% assigned to ambient air (hazard ratio, 1.07; 95% CI, 0.87–1.33; P=0.52). The results were consistent across all predefined subgroups.Conclusions: Routine use of supplemental oxygen in normoxemic patients with suspected myocardial infarction was not found to reduce the composite of all-cause mortality and hospitalization for heart failure, or cardiovascular death within 1 year or during long-term follow-up.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01787110.
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| 46. |
- Jonsdottir, I. H., et al.
(författare)
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Working memory and attention are still impaired after three years inpatients with stress-related exhaustion
- 2017
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Ingår i: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 58:6, s. 504-509
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive impairment is one of the most pronounced symptoms reported by patients with stress-related mental health problems. Impairments related to executive function and to some extent speed and attention are therefore common in patients with stress-related burnout/exhaustion. In this paper we present a follow-up of cognitive performance in patients with stress-related exhaustion several years after they initially sought medical care. Thirty patients and 27 healthy controls, mean age 49 years (SD 6.5) and 55 years (SD 6.7) respectively, were included, all of whom had undergone baseline measurements of neuropsychological functioning. The mean follow-up time was three years. Half of the patients still reported mental health problems at follow-up and over time no major changes in cognitive performance were noted. The patients still performed significantly poorer than controls with regard to cognitive functions, mainly related to speed, attention and memory function. Long-lasting impairment of cognitive functions related to speed, attention and memory function noted in patients with stress-related exhaustion should be acknowledged and taken into consideration during treatment and when discussing a return to work. Follow-up periods longer than three years are needed to explore the persistence of the cognitive impairment. © 2017 Scandinavian Psychological Associations and John Wiley & Sons Ltd
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| 47. |
- Jonsdottir, IH, et al.
(författare)
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Working memory, attention and excecutive functions are still impaired after three years in patients with stress-related exhaustion
- 2017
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Ingår i: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 58:6, s. 504-509
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive impairment is one of the most pronounced symptoms reported by patients with stress-related mental health problems. Impairments related to executive function and to some extent speed and attention are therefore common in patients with stress-related burnout/exhaustion. In this paper we present a follow-up of cognitive performance in patients with stress-related exhaustion several years after they initially sought medical care. Thirty patients and 27 healthy controls, mean age 49 years (SD 6.5) and 55 years (SD 6.7) respectively, were included, all of whom had undergone baseline measurements of neuropsychological functioning. The mean follow-up time was three years. Half of the patients still reported mental health problems at follow-up and over time no major changes in cognitive performance were noted. The patients still performed significantly poorer than controls with regard to cognitive functions, mainly related to speed, attention and memory function. Long-lasting impairment of cognitive functions related to speed, attention and memory function noted in patients with stress-related exhaustion should be acknowledged and taken into consideration during treatment and when discussing a return to work. Follow-up periods longer than three years are needed to explore the persistence of the cognitive impairment.
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| 48. |
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| 49. |
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| 50. |
- Leuer, M., et al.
(författare)
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Somatic mosaicism in hemophilia A: A fairly common event
- 2001
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 69:1, s. 75-87
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the large gene of clotting factor VIII (FVIII) are the most common events leading to severe human bleeding disorder. The high proportion of de novo mutations observed in this gene raises the possibility that a significant proportion of such mutations does not derive from a single germ cell but instead should be attributed to a germline or somatic mosaic originating from a mutation during early embryogenesis. The present study explores this hypothesis by using allele-specific PCR to analyze 61 families that included members who had sporadic severe hemophilia A and known FVIII gene defects. The presence of somatic mosaicisms of varying degrees (0.2%-25%) could be shown in 8 (13%) of the 61 families and has been confirmed by a mutation-enrichment procedure. All mosaics were found in families with point mutations (8 [25%] of 32 families). In the subgroup of 8 families with CpG transitions, the percentage with mosaicism increased to 50% (4 of 8 families). In contrast, no mosaics were observed in 13 families with small deletions/insertions or in 16 families with intron 22 inversions. Our data suggest that mosaicism may represent a fairly common event in hemophilia A. As a consequence, risk assessment in genetic counseling should include consideration of the possibility of somatic mosaicism in families with apparently de novo mutations, especially families with the subtype of point mutations.
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