| 51. |
- Gronhagen, C. M., et al.
(författare)
-
Increased risk of cancer among 3663 patients with cutaneous lupus erythematosus : a Swedish nationwide cohort study
- 2012
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 166:5, s. 1053-1059
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Tidskriftsartikel (refereegranskat)abstract
- Background: Other autoimmune diseases have been associated with higher risks for cancer, and numerous case reports of cutaneous lupus erythematosus (CLE) and different cancer types are available. Objectives: To estimate the overall and specific cancer risks in a nationwide cohort study of patients diagnosed with CLE in Sweden and compare that risk with that in a control cohort without CLE. Methods: A cohort of 3663 individuals with CLE and a matched control cohort from the general population (three controls to each CLE case) without a diagnosis of CLE were derived from the Swedish National Patient Register, 1997-2007, and were electronically linked to the Swedish Cancer Register and the Swedish Cause of Death Register. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to compare the observed vs. the expected numbers of cancers. Results: A total of 183 incident cancers occurred within the observation interval, yielding a HR of 1.8 (95% CI 1.5-2.2) for cancer overall. Median follow-up was 4.1 years. About a fourfold risk increase was seen for buccal cancer, lymphomas, respiratory cancer and nonmelanoma skin cancer. Conclusions: Patients with CLE appear to have an elevated risk for certain cancer types, an increase that remains when excluding patients also diagnosed with systemic lupus erythematosus. Our findings point to the importance of counselling about not smoking and sun avoidance, and underscore the need for specialized monitoring of this patient group along with bench-to-bedside research efforts to clarify pathogenesis.
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| 52. |
- Hagell, Peter, et al.
(författare)
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Effects of method of translation of patient-reported health outcome questionnaires : a randomized study of the translation of the Rheumatoid Arthritis Quality of Life (RAQoL) Instrument for Sweden
- 2010
-
Ingår i: Value in Health. - : Wiley-Blackwell. - 1098-3015 .- 1524-4733. ; 13:4, s. 424-430
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To compare two versions of a questionnaire translated using forward-backward (FB) translation and dual-panel (DP) methodologies regarding preference of wording and psychometric properties.METHODS: The Rheumatoid Arthritis Quality of Life instrument was adapted into Swedish by two independent groups using FB and DP methodologies, respectively. Seven out of thirty resulting items were identical. Nonidentical items were evaluated regarding preference of wording by 23 bilingual Swedes, 50 people with rheumatoid arthritis (RA), and 2 lay panels (n = 11). Psychometric performance was assessed from a postal survey of 200 people with RA randomly assigned to complete one version first and the other 2 weeks later.RESULTS: Preference did not differ among the 23 bilinguals (P = 0.196), whereas patients and lay people preferred DP over FB item versions (P < 0.0001). Postal survey response rates were 74% (FB) and 75% (DP). There were more missing item responses in the FB than the DP version (6.9% vs. 5.6%; P < 0.0001). Floor/ceiling effects were small (FB, 6.1/0%; DP, 4.4/0.7%) and reliability was 0.92 for both versions. Construct validity was similar for both versions. Differential item functioning by version was detected for five items but cancelled out and did not affect estimated person measures.CONCLUSIONS: The DP approach showed advantages over FB translation in terms of preference by the target population and by lay people, whereas there were no obvious psychometric differences. This suggests advantages of DP over FB translation from the patients' perspective, and does not support the commonly held view that FB translation is the "gold standard."
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| 53. |
- Jaworski, G., et al.
(författare)
-
Monte Carlo simulation of a single detector unit for the neutron detector array NEDA
- 2012
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 673, s. 64-72
-
Tidskriftsartikel (refereegranskat)abstract
- A study of the dimensions and performance of a single detector of the future neutron detector array NEDA was performed by means of Monte Carlo simulations, using GEANT4. Two different liquid scintillators were evaluated: the hydrogen based BC501A and the deuterated BC537. The efficiency and the probability that one neutron will trigger a signal in more than one detector were investigated as a function of the detector size. The simulations were validated comparing the results to experimental measurements performed with two existing neutron detectors, with different geometries, based on the liquid scintillator BC501
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| 54. |
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| 55. |
- Kuhn, HG, et al.
(författare)
-
Authors' reply
- 2013
-
Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 74:7
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 56. |
- Lemasson, A., et al.
(författare)
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Pair and single neutron transfer with Borromean He-8
- 2011
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 697:5, s. 454-458
-
Tidskriftsartikel (refereegranskat)abstract
- Direct observation of the survival of Au-199 residues after 2n transfer in the He-8 + Au-197 system and the absence of the corresponding Cu-67 in the He-8 + Cu-65 system at various energies are reported. The measurements of the surprisingly large cross sections for Au-199, coupled with the integral cross sections for the various Au residues, is used to obtain the first model-independent lower limits on the ratio of 2n to in transfer cross sections from He-8 to a heavy target. A comparison of the transfer cross sections for He-6.8 on these targets highlights the differences in the interactions of these Borromean nuclei. These measurements for the most neutron-rich nuclei on different targets highlight the need to probe the reaction mechanism with various targets and represent an experimental advance towards understanding specific features of pairing in the dynamics of dilute nuclear systems.
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| 57. |
- Lemasson, A., et al.
(författare)
-
Reactions with the double-Borromean nucleus 8He
- 2010
-
Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 82:4, s. 044617-
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Tidskriftsartikel (refereegranskat)abstract
- Differential cross sections for elastic-scattering and neutron-transfer reactions along with cross sections for fusion in the He-8+Cu-65 system are reported at energies above the Coulomb barrier (E-lab = 19.9 and 30.6 MeV). The present work demonstrates the feasibility of using inclusive measurements of characteristic in-beam gamma rays with low-intensity (similar to 10(5) pps) radioactive ion beams to obtain the residue cross sections for fusion and neutron transfer. Exclusive measurements of gamma rays in coincidence with light charged particles have been used to further characterize the direct reactions induced by this double-Borromean nucleus. Coupled reaction channels calculations are used to illustrate the important role played by the transfer channels and to help in understanding the influence of the structure of He-8 on the reaction mechanism.
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| 58. |
- Leusink, M., et al.
(författare)
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Cholesteryl Ester Transfer Protein Polymorphisms, Statin Use, and Their Impact on Cholesterol Levels and Cardiovascular Events
- 2014
-
Ingår i: Clinical Pharmacology & Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 95:3, s. 314-320
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Tidskriftsartikel (refereegranskat)abstract
- The association of nonfunctional variants of the cholesteryl ester transfer protein (CETP) with efficacy of statins has been a subject of debate. We evaluated whether three functional CETP variants influence statin efficacy. The effect of CETP genotype on achieved levels of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), and total cholesterol during statin treatment was estimated by meta-analysis of the linear regression outcomes of three studies (11,021 individuals). The effect of these single-nucleotide polymorphisms (SNPs) on statin response in protecting against myocardial infarction (MI) was estimated by meta-analysis of statin x SNP interaction terms from logistic regression in five studies (16,570 individuals). The enhancer SNP rs3764261 significantly increased HDLc by 0.02 mmol/l per T allele (P = 6 x 10-5) and reduced protection against MI by statins (interaction odds ratio (OR) = 1.19 per T allele; P = 0.04). Focusing on functional CETP variants, we showed that in carriers of the rs3764261 T variant, HDLc increased more during statin treatment, and protection against MI by statins appeared to be reduced as compared with those in noncarriers.
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| 59. |
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| 60. |
- Senyigit, M., et al.
(författare)
-
Identification and rejection of scattered neutrons in AGATA
- 2014
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 735, s. 267-276
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Tidskriftsartikel (refereegranskat)abstract
- gamma Rays and neutrons, emitted following spontaneous fission of Cf-252, were measured in an AGATA experiment performed at INFN Laboratori Nazionali di Legnaro in Italy. The setup consisted of four AGATA triple cluster detectors (12 36 fold segmented high purity germanium crystals), placed at a distance of 50 cm from the source, and 16 HELENA BaF2 detectors. The aim of the experiment was to study the interaction of neutrons in the segmented high purity germanium detectors of AGATA and to investigate the possibility to discriminate neutrons and gamma rays with the gamma-ray tracking technique. The BaF2 detectors were used for a time measurement, which gave an independent discrimination of neutrons and gamma rays and which was used to optimise the gamma-ray tracking based neutron rejection methods. It was found that standard gamma-ray tracking, without any additional neutron rejection features, eliminates effectively most of the interaction points clue to recoiling Ge nuclei after elastic scattering of neutrons. Standard Cracking rejects also a significant amount of the events due to inelastic scattering of neutrons in the germanium crystals. Further enhancements of the neutron rejection was obtained by setting conditions on the following quantities, which were evaluated for each event by the Cracking algorithm: energy of the first and second interaction point, difference in the calculated incoming direction of the gamma ray, and figure-of-merit value. The experimental results of Cracking with neutron rejection agree rather well with GEANT4 simulations.
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| 61. |
- Singh, B. S. Nara, et al.
(författare)
-
16(+) Spin-Gap Isomer in (96)Cd
- 2011
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 107:17, s. 172502-
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Tidskriftsartikel (refereegranskat)abstract
- A beta-decaying high-spin isomer in (96)Cd, with a half-life T(1/2) = 0.29(-0.10)(+0.11) s, has been established in a stopped beam rare isotope spectroscopic investigations at GSI (RISING) experiment. The nuclei were produced using the fragmentation of a primary beam of (124)Xe on a (9)Be target. From the half-life and the observed gamma decays in the daughter nucleus, (96)Ag, we conclude that the beta-decaying state is the long predicted 16(+) "spin-gap'' isomer. Shell-model calculations, using the Gross-Frenkel interaction and the pi nu(p(1/2,)g(9/2)) model space, show that the isoscalar component of the neutron-proton interaction is essential to explain the origin of the isomer. Core excitations across the N = Z = 50 gaps and the Gamow-Teller strength, Bd(GT) distributions have been studied via large-scale shell-model calculations using the pi nu(g, d, s) model space to compare with the experimental B(GT) value obtained from the half-life of the isomer.
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| 62. |
- Singh, B. S. Nara, et al.
(författare)
-
Influence of the np interaction on the beta decay of Pd-94
- 2012
-
Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 86:4, s. 041301-
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Tidskriftsartikel (refereegranskat)abstract
- We present results from stopped beam rare isotope spectroscopic investigations at the GSI (RISING) experiment based on the detection of gamma-ray transitions following the beta decay of Pd-94. A comparison between the measured low-lying level scheme of Rh-94 and the prediction from shell-model calculations reveals the important roles of the g(7/2) and g(9/2) orbitals in explaining the structural features. The low values of the Gamow-Teller strengths B(GT) can be attributed to the influence of the neutron-proton interaction, which gives rise to an increased seniority mixing for the nuclear states, thereby leading to a fragmentation of the strength to several daughter levels. These results provide further strong indications that Pd-94 resides in the middle of a structural transition region in the Pd isotopes as the N = Z line is approached.
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| 63. |
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| 64. |
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| 65. |
- Taneja, A, et al.
(författare)
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Application of ED-optimality to screening experiments for analgesic compounds in an experimental model of neuropathic pain.
- 2012
-
Ingår i: Journal of Pharmacokinetics and Pharmacodynamics. - : Springer Science and Business Media LLC. - 1567-567X .- 1573-8744. ; 39:6, s. 673-681
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Tidskriftsartikel (refereegranskat)abstract
- In spite of the evidence regarding high variability in the response to evoked pain, little attention has been paid to its impact on the screening of drugs for inflammatory and neuropathic pain. In this study, we explore the feasibility of introducing optimality concepts to experimental protocols, enabling estimation of parameter and model uncertainty. Pharmacokinetic (PK) and pharmacodynamic data from different experiments in rats were pooled and modelled using nonlinear mixed effects modelling. Pain data on gabapentin and placebo-treated animals were generated in the complete Freund's adjuvant model of neuropathic pain. A logistic regression model was applied to optimise sampling times and dose levels to be used in an experimental protocol. Drug potency (EC(50)) and interindividual variability (IIV) were considered the parameters of interest. Different experimental designs were tested and validated by SSE (stochastic simulation and estimation) taking into account relevant exposure ranges. The pharmacokinetics of gabapentin was described by a two-compartment PK model with first order absorption (CL = 0.159 l h(-1), V(2) = 0.118 l, V(3) = 0.253 l, Ka = 0.26 h(-1), Q = 1.22 l h(-1)). Drug potency (EC(50)) for the anti-allodynic effects was estimated to be 1400 ng ml(-1). Protocol optimisation improved bias and precision of the EC50 by 6 and 11.9. %, respectively, whilst IIV estimates showed improvement of 31.89 and 14.91 %, respectively. Our results show that variability in behavioural models of evoked pain response leads to uncertainty in drug potency estimates, with potential impact on the ranking of compounds during screening. As illustrated for gabapentin, ED-optimality concepts enable analysis of discrete data taking into account experimental constraints.
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| 66. |
- Wadsworth, R., et al.
(författare)
-
Spin-gap Isomer in 96Cd
- 2012
-
Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6596 .- 1742-6588. ; 381:1
-
Tidskriftsartikel (refereegranskat)abstract
- Evidence has been obtained for the existence of the long predicted 16+ spin-gap isomer in 96Cd. The decay of the isomer was identified and studied following the use of an 850 MeV/u beam of 124Xe impinging on a Be target and the fragment recoil separator at the GSI Laboratory. Gamma decays from the fragments were detected using the RISING gamma ray array, in its stopped beam configuration, plus a silicon active stopper. The data obtained have been compared with shell model predictions, which indicate that the isoscalar neutron-proton interaction plays a key role in the formation of the isomer.
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| 67. |
- Al Haj, Mahmoud, et al.
(författare)
-
Effect of Dehydration in the Presence and Absence of the Angiotensin Receptor Blocker Losartan on Blood Constituents in the Camel
- 2011
-
Ingår i: Journal of Medical Sciences. - : Hamdan Medical Journal. - 1996-3262 .- 1996-3270. ; 4:2, s. 73-78
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Dromedary camels are extremely well adapted to periods of water deprivation. The physiological mechanisms underlying this adaptation, however, are imperfectly understood. It is likely that the renin-angiotensin system plays an important role although few studies have addressed this possibility in the camel. Accordingly, the effects of long term dehydration alone and with angiotensin II type 1 receptor blocker, losartan, on whole blood and serum constituents were studied in camels.Methods:Twenty eight male camels 3-4 years old were studied while under shade during summer in the Gulf-region, where the ambient temperature was above 40 degree Celsius. The camels were divided into three groups: a control group(n=6) was allowed free access to feed and water, a dehydration group (n=16) was given food ad-lib during 20days of total water deprivation, and a dehydration plus losartan (losartan) group (n=6) which received losartan 5mg/Kg daily by intravenous injection during 20 days of dehydration. Results: The body weight of the losartan group decreased by nearly 39.1% across dehydration whereas the reduction in body weight for the dehydration group was nearly 34.5% compared to controls. There was a significant increase in the packed cell volume (p<0.05) and leucocytes count (p<0.01) in the losartan group compared to controls. However, the mean corpuscular volume was significantly higher (p<0.05) in the dehydration group compared to controls. We observed major, statistically significant increases in serum urea (p<0.01) and creatinine (p<0.05) levels in the dehydration and losartan groups compared to controls. By the end of the period ofwater restriction, serum levels of gamma glutamyl transferase were significantly (p<0.01) lower in the losartan group compared to controls.Conclusion: The results of our experiment show that dehydration alone or in combination with Angiotensin II receptor blocker has major effects on the biochemical and hematological parameters of the camel blood.
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| 68. |
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| 69. |
- Ali Haj, Mahmoud, et al.
(författare)
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Effects of Dehydration and Blockade of Angiotensin II AT1 Receptor on Stress Hormones and Anti-Oxidants in the one-humped camel
- 2013
-
Ingår i: BMC Veterinary Research. - : Springer Science and Business Media LLC. - 1746-6148. ; 9, s. 232-
-
Tidskriftsartikel (refereegranskat)abstract
- Our objectives were to document and compare plasma levels of Catecholamines, Cortisol,Glutathione and Malondialdehyde in camels after long term dehydration (20 days) in the presenceor absence of angiotensin II AT1 receptor blocker (Losartan) versus levels in non-dehydratedcamels; and to record the effects on glutathione and malondialdehyde activity in liver and kidneyhomogenate in the one-humped camel. Eighteen male camels were used in this study, sixcontrols, six dehydrated and treated with losartan (5mg/kg daily) and six were dehydrated withouttreatment. Our results revealed significant decrease (P<0.05) in plasma epinephrine level in bothtreated and dehydrated camels; while, Plasma norepinephrine showed significant increase in bothdehydrated groups (P< 0.01). Levels of plasma dopamine were also significantly increased (P<0.01) in both dehydrated groups compared to control camels.Plasma levels of cortisol increased significantly across dehydration with or without losartanadministration (P<0.01) compared with time-matched levels in control camels. Losartan had nosignificant modulating effect on the cortisol response to dehydration.Plasma, liver and kidney homogenates revealed significant increase (P<0.05) in glutathione levelsin both dehydrated groups compared to control.Plasma, liver and kidney homogenates for malondialdehyde levels in both treated and dehydratedcamels also showed significant increase (P<0.05 & P<0.01) compared to controls.In conclusion, our study demonstrates that the effect of dehydration with or without losartaninduced oxidative stress in these camels, leading to significant changes in plasma catecholaminesand cortisol levels, together with significant increments in glutathione and malondialdehydeactivities in plasma, liver and kidney homogenate to counter act the damaging effect of the freeradicals in the dehydrated camels.
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| 70. |
- Andappan, Murugaiah M. S., et al.
(författare)
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From the First Selective Non-Peptide AT(2) Receptor Agonist to Structurally Related Antagonists
- 2012
-
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:5, s. 2265-2278
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Tidskriftsartikel (refereegranskat)abstract
- A para substitution pattern of the phenyl ring is a characteristic feature of the first reported selective AT(2) receptor agonist M024/C21 (1) and all the nonpeptidic AT(2) receptor agonists described so far. Two series of compounds structurally related to 1 but with a meta substitution pattern have now been synthesized and biologically evaluated for their affinity to the AT(1) and AT(2) receptors. A high AT(2)/AT(1) receptor selectivity was obtained with all 41 compounds synthesized, and the majority exhibited K-i ranging from 2 to 100 nM. Five compounds were evaluated for their functional activity at the AT(2) receptor, applying a neurite outgrowth assay in NG108-15 cells.. Notably, four of the five compounds, with representatives from both series, acted as potent AT(2) receptor antagonists. These compounds were found to be considerably more effective than PD 123,319, the standard AT(2) receptor antagonist used in most laboratories. No AT(2) receptor antagonists were previously reported among the derivatives with a para substitution pattern. Hence, by a minor modification of the agonist 1 it could be transformed into the antagonist, compound 38. These compounds should serve as valuable tools in the assessment of the role of the AT(2) receptor in more complex physiological models.
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| 71. |
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| 72. |
- Bäckström, Torbjörn, et al.
(författare)
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Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons
- 2011
-
Ingår i: Neuroscience. - Oxford : Elsevier BV. - 0306-4522 .- 1873-7544. ; 191:Special issue, s. 46-54
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Forskningsöversikt (refereegranskat)abstract
- Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%-8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%-8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane C1(-) gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote disinhibition, and hence excitability. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain. (C) 2011 Published by Elsevier Ltd on behalf of IBRO.
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| 73. |
- Chasman, D. I., et al.
(författare)
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Genetic Determinants of Statin-Induced Low-Density Lipoprotein Cholesterol Reduction The Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) Trial
- 2012
-
Ingår i: Circulation-Cardiovascular Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 1942-325X .- 1942-3268. ; 5:2, s. 257-264
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Tidskriftsartikel (refereegranskat)abstract
- Background-In statin trials, each 20 mg/dL reduction in cholesterol results in a 10-15% reduction of annual incidence rates for vascular events. However, interindividual variation in low-density lipoprotein cholesterol (LDL-C) response to statins is wide and may partially be determined on a genetic basis. Methods and Results-A genome-wide association study of LDL-C response was performed among a total of 6989 men and women of European ancestry who were randomly allocated to either rosuvastatin 20 mg daily or placebo. Single nucleotide polymorphisms (SNPs) for genome-wide association (P<5x10(-8)) with LDL-C reduction on rosuvastatin were identified at ABCG2, LPA, and APOE, and a further association at PCSK9 was genome-wide significant for baseline LDL-C and locus-wide significant for LDL-C reduction. Median LDL-C reductions on rosuvastatin were 40, 48, 51, 55, 60, and 64 mg/dL, respectively, among those inheriting increasing numbers of LDL-lowering alleles for SNPs at these 4 loci (P trend=6.2x10(-20)), such that each allele approximately doubled the odds of percent LDL-C reduction greater than the trial median (odds ratio, 1.9; 95% confidence interval, 1.8-2.1; P=5.0x10(-41)). An intriguing additional association with sub-genome-wide significance (P<1x10(-6)) was identified for statin related LDL-C reduction at IDOL, which mediates posttranscriptional regulation of the LDL receptor in response to intracellular cholesterol levels. In candidate analysis, SNPs in SLCO1B1 and LDLR were confirmed as associated with LDL-C lowering, and a significant interaction was observed between SNPs in PCSK9 and LDLR. Conclusions-Inherited polymorphisms that predominantly relate to statin pharmacokinetics and endocytosis of LDL particles by the LDL receptor are common in the general population and influence individual patient response to statin therapy. (Circ Cardiovasc Genet. 2012;5:257-264.)
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| 74. |
- Chen, S., et al.
(författare)
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Novel Zn-Doped Al2O3 Charge Storage Medium for Light-Erasable In-Ga-Zn-O TFT Memory
- 2013
-
Ingår i: IEEE Electron Device Letters. - 0741-3106 .- 1558-0563. ; 34:8, s. 1008-1010
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Tidskriftsartikel (refereegranskat)abstract
- A novel Zn-doped Al2O3 (ZAO) layer prepared by atomic layer deposition (ALD) is used as the charge storage medium in an In-Ga-Zn-O thin-film-transistor memory. The gate insulating stack of Al2O3/ZAO/Al2O3 is assembled in a single ALD step, and is found to possess a high electron storage capacity due to very deep defect levels. The memory device shows a threshold voltage shift as large as 6.38 V after a +15V/1 ms programming pulse, and quite good charge retention. Once programmed, the memory can be only light erased. The underlying mechanisms are discussed with the assistance of density functional theory calculations.
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| 75. |
- Chu, A. Y., et al.
(författare)
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Pharmacogenetic Determinants of Statin-Induced Reductions in C-Reactive Protein
- 2012
-
Ingår i: Circulation-Cardiovascular Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 1942-325X .- 1942-3268. ; 5:1, s. 58-65
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Tidskriftsartikel (refereegranskat)abstract
- Background-In randomized trials, statins reduce plasma levels of C-reactive protein (CRP) and low-density lipoprotein cholesterol (LDL-C), and the magnitude of event reduction relates to on-treatment levels of both. However, whether different mechanisms underlie statin-induced CRP and LDL-C reduction is unknown. Methods and Results-We performed a study to evaluate potential genetic determinants of CRP response using genome-wide genetic data from a total of 6766 participants of European ancestry randomly allocated to 20 mg/d of rosuvastatin or placebo in the JUPITER trial. Among 3386 rosuvastatin-allocated individuals, both CRP and LDL-C levels were reduced by 50% after 12 months of therapy (P<0.001 for both) and essentially uncorrelated (r(2)<0.03). No variants in the 3 genes (ABCG2, LPA, and APOE) that previously showed genome-wide association with LDL-C reduction in this cohort and none of the candidate single-nucleotide polymorphisms associated with LDL-C reduction were associated with rosuvastatin-induced CRP change after multiple testing correction. Among candidate single-nucleotide polymorphisms selected from prior genetic analyses of baseline CRP, CRP reduction was associated with rs2794520 in CRP (mean, -3.5% [SE, 2.0%] change in CRP per minor allele; P=6.4 x 10(-4)) and with rs2847281 in PTPN2 (mean, 3.7% [SE, 1.9%] change in CRP per minor allele; P=7.4 x 10(-4)). These associations remained significant after multiple testing correction but were not significant in a formal test of interaction. Neither variant was associated with rosuvastatin-induced LDL-C reduction or with CRP reduction among 3380 placebo-allocated JUPITER participants. Conclusions-The genetic determinants of rosuvastatin-induced CRP reduction differ from, and are largely independent of, the major pharmacogenetic determinants of rosuvastatin-induced LDL-C reduction. This supports the hypothesis that differing pathways may mediate the anti-inflammatory and lipid-lowering properties of statin therapy. (Circ Cardiovasc Genet. 2012;5:58-65.)
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| 76. |
- Cloots, R. J. H., et al.
(författare)
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Micromechanics of diffuse axonal injury : influence of axonal orientation and anisotropy
- 2011
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Ingår i: Biomechanics and Modeling in Mechanobiology. - : Springer Science and Business Media LLC. - 1617-7959 .- 1617-7940. ; 10:3, s. 413-422
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Tidskriftsartikel (refereegranskat)abstract
- Multiple length scales are involved in the development of traumatic brain injury, where the global mechanics of the head level are responsible for local physiological impairment of brain cells. In this study, a relation between the mechanical state at the tissue level and the cellular level is established. A model has been developed that is based on pathological observations of local axonal injury. The model contains axons surrounding an obstacle (e.g., a blood vessel or a brain soma). The axons, which are described by an anisotropic fiber-reinforced material model, have several physically different orientations. The results of the simulations reveal axonal strains being higher than the applied maximum principal tissue strain. For anisotropic brain tissue with a relatively stiff inclusion, the relative logarithmic strain increase is above 60%. Furthermore, it is concluded that individual axons oriented away from the main axonal direction at a specific site can be subjected to even higher axonal strains in a stress-driven process, e.g., invoked by inertial forces in the brain. These axons can have a logarithmic strain of about 2.5 times the maximum logarithmic strain of the axons in the main axonal direction over the complete range of loading directions. The results indicate that cellular level heterogeneities have an important influence on the axonal strain, leading to an orientation and location-dependent sensitivity of the tissue to mechanical loads. Therefore, these effects should be accounted for in injury assessments relying on finite element head models.
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| 77. |
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| 78. |
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| 79. |
- Danik, J. S., et al.
(författare)
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Lack of association between SLCO1B1 polymorphisms and clinical myalgia following rosuvastatin therapy
- 2013
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 165:6, s. 1008-1014
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Tidskriftsartikel (refereegranskat)abstract
- Background Carriers of the rs4363657C and rs4149056C alleles in SLCO1B1 have increased myopathic complaints when taking simvastatin. Whether rosuvastatin has a similar effect is uncertain. This study assesses whether SLCO1B1 polymorphisms relate to clinical myalgia after rosuvastatin therapy. Methods In the JUPITER trial, participants without prior cardiovascular disease or diabetes who had low-density lipoprotein cholesterol <130 mg/dL and C-reactive protein ≥2 mg/L were randomly allocated to rosuvastatin 20 mg or placebo and followed for the first cardiovascular disease events and adverse effects. We evaluated the effect of rs4363657 and rs4149056 in SLCO1B1, which encodes organic anion–transporting polypeptide OATP1B1, a regulator of hepatic statin uptake, on clinically reported myalgia. Results Among 4,404 participants allocated to rosuvastatin, clinical myalgia occurred with a rate of 4.1 events per 100 person-years as compared with 3.7 events per 100 person-years among 4,378 participants allocated to placebo (hazard ratio [HR] 1.13, 95% CI 0.98-1.30). Among those on rosuvastatin, there were no differences in the rate of myalgia among those with the rs4363657C (HR 0.95, 95% CI 0.79-1.14 per allele) or the rs4149056C allele (HR 0.95, 95% CI 0.79-1.15 per allele) compared with those without the C allele. Similar null data were observed when the myalgia definition was broadened to include muscle weakness, stiffness, or pain. None of the 3 participants on rosuvastatin or the 3 participants on placebo with frank myopathy had the minor allele at either polymorphism. Conclusion There appears to be no increased risk of myalgia among users of rosuvastatin who carry the rs4363657C or the rs4149056C allele in SLCO1B1.
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| 80. |
- de Frias, Cindy M., et al.
(författare)
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Influence of COMT Gene Polymorphism on fMRI-assessed Sustained and Transient Activity during a Working Memory Task
- 2010
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Ingår i: Journal of cognitive neuroscience. - Cambridge, Mass. : MIT Press. - 0898-929X .- 1530-8898. ; 22:7, s. 1614-1622
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Tidskriftsartikel (refereegranskat)abstract
- The catechol O-methyltransferase (COMT) gene-encoding an enzyme that is essential for the degradation of dopamine (DA) in prefrontal cortex (PFC)-contains a single nucleotide polymorphism (val/met) important for cognition. According to the tonic-phasic hypothesis, individuals carrying the low-enzyme- activity allele (met) are characterized by enhanced tonic DA activity in PFC, promoting sustained cognitive representations in working memory. Val carriers have reduced tonic but enhanced phasic dopaminergic activity in subcortical regions, enhancing cognitive flexibility. We tested the tonic-phasic DA hypothesis by dissociating sustained and transient brain activity during performance on a 2-back working memory test using mixed blocked/event-related functional magnetic resonance imaging. Participants were men recruited from a random sample of the population (the Betula study) and consisted of 11 met/met and 11 val/val carriers aged 50 to 65 years, matched on age, education, and cognitive performance. There were no differences in 2-back performance between genotype groups. Met carriers displayed a greater transient medial temporal lobe response in the updating phase of working memory, whereas val carriers showed a greater sustained PFC activation in the maintenance phase. These results support the tonic-phasic theory of DA function in elucidating the specific phenotypic influence of the COMT val(158)met polymorphism on different components of working memory.
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| 81. |
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| 82. |
- Drevenhorn, Eva, et al.
(författare)
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Consultation training of nurses for cardiovascular prevention - A randomized study of 2 years duration
- 2012
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Ingår i: Blood Pressure. - : Informa Healthcare. - 0803-7051 .- 1651-1999. ; 21:5, s. 293-299
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to increase patients adherence to the treatment of hypertension through the consultation training of nurses. Thirty-three nurses were included in the study. In the intervention group (IG), 19 nurses took part in a 3-day residential training course on the Stages of Change model, Motivational Interviewing and guidelines for cardiovascular prevention, and recruited 153 patients. Sixteen nurses in the control group (CG) recruited 59 patients. A decrease in systolic and diastolic blood pressure and total cholesterol was noticed in both groups over the 2 years. Heart rate (p = 0.027), body mass index (p = 0.019), weight (p = 0.0001), waist (p = 0.041), low-density lipoprotein-cholesterol (p = 0.0001), the waist-hip ratio (p = 0.024), and perceived stress (p = 0.001) decreased to any great extent only in the IG. After 2 years, 52.6% of the patients in the IG (p = 0.13) reached the target of andlt;= 140/90 mmHg in blood pressure compared with 39.2% in the CG. For self-reported physical activity, there was a significant (p = 0.021) difference between the groups. The beneficial effects of the consultation training on patients weight parameters, physical activity, perceived stress and the proportion of patients who achieved blood pressure control emphasize consultation training and the use of behavioural models in motivating patients to adhere to treatment.
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| 83. |
- Eilertsen, M. E. B., et al.
(författare)
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Impact of Social Support on Bereaved Siblings' Anxiety: A Nationwide Follow-Up
- 2013
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Ingår i: Journal of Pediatric Oncology Nursing. - : SAGE Publications. - 1043-4542 .- 1532-8457. ; 30:6, s. 301-310
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:To assess adolescent and young adult siblings' perception of social support prior to and following the loss of their brother or sister to cancer, 2 to 9 years earlier, and their anxiety at follow-up. Method: In 2009, 174 (73%) bereaved siblings (12-25 years) participated in a nationwide, long-term follow-up study in Sweden using an anonymous study-specific questionnaire. The Hospital Anxiety and Depression Scale was used to measure self-assessed anxiety. Results: Siblings had a higher risk of anxiety if they perceived their need for social support was unsatisfied during their brother or sisters' last month before death, relative risk (RR) = 3.6 (95% confidence interval [CI] = 1.8-7.3); time after death, RR = 2.9 (95% CI = 1.5-5.6); and at follow-up, RR = 3.8 (95% CI = 2.0-7.2). Furthermore, a higher risk for anxiety was shown for siblings if they did not perceive that their parents and neighbors cared for them after their brother or sisters' death, RR = 2.7 (95% CI = 1.3-5.5), RR = 5.4 (95% CI = 1.3-21.9), respectively. Conclusion: Bereaved siblings had a greater probability to report self-assessed anxiety if they perceived that their need for social support was not satisfied prior to and following death. Information from both nurses and other health care professionals to families about the impact of social support may contribute to lessen the siblings' risk of anxiety.
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| 84. |
- Filipovikj, Predrag, et al.
(författare)
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2014 IEEE 22nd International Requirements Engineering Conference, RE 2014 - Proceedings
- 2014
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Ingår i: 2014 IEEE 22nd International Requirements Engineering Conference, RE 2014 - Proceedings. - 9781479930333 ; , s. 444-450
-
Konferensbidrag (refereegranskat)abstract
- The importance of using formal methods and techniques for verification of requirements in the automotive industry has been greatly emphasized with the introduction of the new ISO26262 standard for road vehicles functional safety. The lack of support for formal modeling of requirements still represents an obstacle for the adoption of the formal methods in industry. This paper presents a case study that has been conducted in order to evaluate the difficulties inherent to the process of transforming the system requirements from their traditional written form into semi-formal notation. The case study focuses on a set of non-structured functional requirements for the Electrical and Electronic (E/E) systems inside heavy road vehicles, written in natural language, and reassesses the applicability of the extended Specification Pattern System (SPS) represented in a restricted English grammar. Correlating this experience with former studies, we observe that, as previously claimed, the concept of patterns is likely to be generally applicable for the automotive domain. Additionally, we have identified some potential difficulties in the transformation process, which were not reported by the previous studies and will be used as a basis for further research.
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| 85. |
- Fransson, Rebecca, 1980-, et al.
(författare)
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Constrained H-Phe-Phe-NH2 Analogues With High Affinity to the Substance P 1-7 Binding Site and With Improved Metabolic Stability and Cell Permeability
- 2013
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 56:12, s. 4953-4965
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Tidskriftsartikel (refereegranskat)abstract
- We recently reported the discovery of H-Phe-Phe-NH2 as a small and high affinity ligand for the substance P 1-7 (SP1-7, H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH) specific binding site and its intriguing ability to reduce neuropathic pain. With the overall aim to develop stable and orally bioavailable SP1-7 mimetics, the dipeptide was chosen as a lead compound. Herein the structure-activity relationship (SAR) of a set of modified H-Phe-Phe-NH2 analogues is presented together with their potential active uptake by PEPT1 transporter, intestinal permeability, and metabolic stability. Local constraints via peptide backbone methylation or preparation of cyclized analogues based on pyrrolidine were evaluated and were shown to significantly improve the in vitro pharmacokinetic properties. The SAR was rationalized by deriving a plausible binding pose for the high affinity ligands. Rigidification using a 3-phenylpyrrolidine moiety in the C-terminal of H-Phe-Phe-NH2 resulted in high affinity and improved intrinsic clearance and intestinal epithelial permeability.
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| 86. |
- Ghasemzadeh, Nasim
(författare)
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Application of Artificial Gel Antibodies for the Detection and Quantification of Proteins in Biological Fluids
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The molecular-imprinting method has previously been used for the synthesis of artificial gel antibodies, highly selective for various proteins. In present study, we have synthesized artificial gel antibodies against haemoglobin, albumin and different forms of growth hormone with the aim to develop a simple and rapid procedure to measure the concentration of these protein biomarkers in samples of clinical interest. A spectrophotometric method was developed to design a standard curve in the form of a straight line, whereby the true absorption (not the recorded “apparent” absorption) was plotted against a known protein concentration. The procedure, applied to quantitative analysis of albumin in human plasma and cerebrospinal fluid (CSF) from patients with ALS, indicated that the concentration of this protein was significantly enhanced in CSF from patients with amyotrophic lateral sclerosis (ALS), compared to control samples. A low level of albumin was observed in plasma from ALS patients compared to controls. Additionally, free zone electrophoresis was employed to detect human growth hormone (GH) activity in hormone preparations purified from human pituitaries. We have successfully synthesized antibodies capable of discriminating between dimeric and monomeric GH in samples of clinical origin. To quantify these proteins a calibration curve has been designed, i.e. a plot of the electrophoretic mobility of the complex GH/gel antibody against the protein concentration in the sample, for instance serum or CSF. This method was also employed for qualitative and quantitative determinations of Somatropin, a non-glycosylated GH and glycosylated-GH in a body liquid. Our results indicate that by this technique one can “fish out” with high accuracy various proteins from both body fluids containing a great number of other proteins. It might well apply also to biomarker proteins for other diseases.
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| 87. |
- Hagell, Peter, et al.
(författare)
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Effects of Method of Translation of Patient-Reported Health Outcome Questionnaires: A Randomized Study of the Translation of the Rheumatoid Arthritis Quality of Life (RAQoL) Instrument for Sweden.
- 2010
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Ingår i: Value in Health. - : Elsevier BV. - 1098-3015. ; 13, s. 424-430
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT Aims: To compare two versions of a questionnaire translated using forward-backward (FB) translation and dual-panel (DP) methodologies regarding preference of wording and psychometric properties. Methods: The Rheumatoid Arthritis Quality of Life instrument was adapted into Swedish by two independent groups using FB and DP methodologies, respectively. Seven out of thirty resulting items were identical. Nonidentical items were evaluated regarding preference of wording by 23 bilingual Swedes, 50 people with rheumatoid arthritis (RA), and 2 lay panels (n = 11). Psychometric performance was assessed from a postal survey of 200 people with RA randomly assigned to complete one version first and the other 2 weeks later. Results: Preference did not differ among the 23 bilinguals (P = 0.196), whereas patients and lay people preferred DP over FB item versions (P < 0.0001). Postal survey response rates were 74% (FB) and 75% (DP). There were more missing item responses in the FB than the DP version (6.9% vs. 5.6%; P < 0.0001). Floor/ceiling effects were small (FB, 6.1/0%; DP, 4.4/0.7%) and reliability was 0.92 for both versions. Construct validity was similar for both versions. Differential item functioning by version was detected for five items but cancelled out and did not affect estimated person measures. Conclusions: The DP approach showed advantages over FB translation in terms of preference by the target population and by lay people, whereas there were no obvious psychometric differences. This suggests advantages of DP over FB translation from the patients' perspective, and does not support the commonly held view that FB translation is the "gold standard."
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| 88. |
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| 89. |
- Holmqvist, M. E., et al.
(författare)
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Rapid increase in myocardial infarction risk following diagnosis of rheumatoid arthritis amongst patients diagnosed between 1995 and 2006
- 2010
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 268:6, s. 578-585
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Tidskriftsartikel (refereegranskat)abstract
- Holmqvist ME, Wedren S, Jacobsson LTH, Klareskog L, Nyberg F, Rantapaa-Dahlqvist S, Alfredsson L, Askling J (Institute of Environmental Medicine, Karolinska Institutet, Stockholm; Karolinska Institutet/Karolinska Hospital, Stockholm; Malmo University Hospital, Malmo; AstraZeneca R&D, Molndal; and Umea University Hospital, Umea, Sweden) Rapid increase in myocardial infarction risk following diagnosis of rheumatoid arthritis amongst patients diagnosed between 1995 and 2006. J Intern Med 2010; 268: 578-585. The risk of ischaemic heart disease (IHD), and in particular myocardial infarction (MI), is increased amongst patients with established rheumatoid arthritis (RA). Few studies have included contemporary patients with RA. We recently reported that the risk of IHD is not elevated before the onset of RA symptoms. However, when, in relation to RA diagnosis, the risk is increased is unknown. Objective. To assess the risk of MI and other IHD events amongst patients diagnosed with RA during the last decade and within 18 months following RA symptom onset, compared to the general population, by time since RA diagnosis, year of RA diagnosis and by rheumatoid factor (RF) status. Methods and patients. A Swedish inception cohort of RA (n = 7469) diagnosed between 1995 and 2006 and a matched general population comparator cohort (n = 37 024), was identified and linked to national registers of morbidity and mortality from IHD. Relative risks (RRs) of MI and other IHD events were estimated using Cox regression. Results. During follow-up, 233 patients with RA and 701 controls developed a first MI, corresponding to an overall RR of MI of 1.6 (95% confidence interval 1.4, 1.9). Increased risks of MI were already detected within 1-4 years following RA diagnosis, as well as in patients diagnosed with RA during the last 5 years, in RF-negative patients and for transmural as well as nontransmural MIs. Conclusions. MI risk increases rapidly following RA diagnosis, suggesting the importance of additional mechanisms other than atherosclerosis. The elevated short-term risk is present amongst patients diagnosed in recent years, underscoring the importance of MI prevention from the time of RA diagnosis.
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| 90. |
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| 91. |
- Holtta-Vuori, M., et al.
(författare)
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Zebrafish: gaining popularity in lipid research
- 2010
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Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 429:2, s. 235-242
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Tidskriftsartikel (refereegranskat)abstract
- Zebrafish are an increasingly popular vertebrate model organism in which to study biological phenomena. It has been widely used, especially ill developmental biology and neurobiology, and many aspects of its development and physiology are similar to those of mammals. The popularity of zebrafish relies on its relatively low cost, rapid development and ease of genetic manipulation. Moreover, the optical transparency of the developing fish together with novel imaging techniques enable the direct visualization of complex phenomena at the level of the entire organism. This potential is now also being increasingly appreciated by the lipid research community. In the present review we summarize basic information on the lipid composition and distribution in zebrafish tissues, including lipoprotein metabolism, intestinal lipid absorption, the yolk lipids and their mobilization, as well as lipids in the nervous system. We also discuss studies in which zebrafish have been employed for the visualization of whole-body lipid distribution and trafficking. Finally, recent advances in using zebrafish as a model for lipid-related diseases, including atherosclerosis, obesity, diabetes and hepatic steatosis are highlighted. As the insights into zebrafish lipid metabolism increase, it is likely that zebrafish as a model organism will become an increasingly powerful tool in lipid research.
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| 92. |
- Javier Egea, Francisco, et al.
(författare)
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Design and Test of a High-Speed Flash ADC Mezzanine Card for High-Resolution and Timing Performance in Nuclear Structure Experiments
- 2013
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Ingår i: IEEE Transactions on Nuclear Science. - 0018-9499 .- 1558-1578. ; 60:5, s. 3526-3531
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Tidskriftsartikel (refereegranskat)abstract
- This work describes new electronics for the EX-OGAM2 (HP-Ge detector array) and NEDA (BC501A-based neutron detector array). A new digitizing card with high resolution has been designed for gamma-ray and neutron spectroscopy experiments. The higher bandwidth requirement of the NEDA signals, together with the necessity for accuracy, require a high sampling rate in order to preserve the shape for real-time Pulse Shape Analysis (PSA). The PSA is of paramount importance for the NEDA to discriminate between neutrons and gamma-ray signals. Both high resolution and high speed parameters are often difficult to achieve in a single electronic unit. These constraints, together with the need to build new digitizing electronics to improve performance and flexibility of signal analysis in nuclear physics experiments, led to the development a new FADC mezzanine card. In this work, the design and development are described, including the characterization procedure and the preliminary measurement results.
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| 93. |
- Johansson, Eva, et al.
(författare)
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Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting : the Scandinavian Prostate Cancer Group-4 randomised trial
- 2011
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 12:9, s. 891-899
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: For men with localised prostate cancer, surgery provides a survival benefit compared with watchful waiting. Treatments are associated with morbidity. Results for functional outcome and quality of life are rarely reported beyond 10 years and are lacking from randomised settings. We report results for quality of life for men in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after a median follow-up of more than 12 years.METHODS: All living Swedish and Finnish men (400 of 695) randomly assigned to radical prostatectomy or watchful waiting in SPCG-4 from 1989 to 1999 were included in our analysis. An additional 281 men were included in a population-based control group matched for region and age. Physical symptoms, symptom-induced stress, and self-assessed quality of life were evaluated with a study-specific questionnaire. Longitudinal data were available for 166 Swedish men who had answered quality-of-life questionnaires at an earlier timepoint.FINDINGS: 182 (88%) of 208 men in the radical prostatectomy group, 167 (87%) of 192 men in the watchful-waiting group, and 214 (76%) of 281 men in the population-based control group answered the questionnaire. Men in SPCG-4 had a median follow-up of 12·2 years (range 7-17) and a median age of 77·0 years (range 61-88). High self-assessed quality of life was reported by 62 (35%) of 179 men allocated radical prostatectomy, 55 (34%) of 160 men assigned to watchful waiting, and 93 (45%) of 208 men in the control group. Anxiety was higher in the SPCG-4 groups (77 [43%] of 178 and 69 [43%] of 161 men) than in the control group (68 [33%] of 208 men; relative risk 1·42, 95% CI 1·07-1·88). Prevalence of erectile dysfunction was 84% (146 of 173 men) in the radical prostatectomy group, 80% (122 of 153) in the watchful-waiting group, and 46% (95 of 208) in the control group and prevalence of urinary leakage was 41% (71 of 173), 11% (18 of 164), and 3% (six of 209), respectively. Distress caused by these symptoms was reported significantly more often by men allocated radical prostatectomy than by men assigned to watchful waiting. In a longitudinal analysis of men in SPCG-4 who provided information at two follow-up points 9 years apart, 38 (45%) of 85 men allocated radical prostatectomy and 48 (60%) of 80 men allocated watchful waiting reported an increase in number of physical symptoms; 50 (61%) of 82 and 47 (64%) of 74 men, respectively, reported a reduction in quality of life.INTERPRETATION: For men in SPCG-4, negative side-effects were common and added more stress than was reported in the control population. In the radical prostatectomy group, erectile dysfunction and urinary leakage were often consequences of surgery. In the watchful-waiting group, side-effects can be caused by tumour progression. The number and severity of side-effects changes over time at a higher rate than is caused by normal ageing and a loss of sexual ability is a persistent psychological problem for both interventions. An understanding of the patterns of side-effects and time dimension of their occurrence for each treatment is important for full patient information.
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| 94. |
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| 95. |
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| 96. |
- Järvinen, Tiina M., et al.
(författare)
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Polymorphisms of the ITGAM Gene Confer Higher Risk of Discoid Cutaneous Than of Systemic Lupus Erythematosus
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:11, s. e14212-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lupus erythematosus (LE) is a heterogeneous disease ranging from mainly skin-restricted manifestations (discoid LE [DLE] and subacute cutaneous LE) to a progressive multisystem disease (systemic LE [SLE]). Genetic association studies have recently identified several strong susceptibility genes for SLE, including integrin alpha M (ITGAM), also known as CD11b, whereas the genetic background of DLE is less clear. Principal Findings: To specifically investigate whether ITGAM is a susceptibility gene not only for SLE, but also for cutaneous DLE, we genotyped 177 patients with DLE, 85 patients with sporadic SLE, 190 index cases from SLE families and 395 population control individuals from Finland for nine genetic markers at the ITGAM locus. SLE patients were further subdivided by the presence or absence of discoid rash and renal involvement. In addition, 235 Finnish and Swedish patients positive for Ro/SSA-autoantibodies were included in a subphenotype analysis. Analysis of the ITGAM coding variant rs1143679 showed highly significant association to DLE in patients without signs of systemic disease (P-value = 4.73x10(-11), OR = 3.20, 95% CI = 2.23-4.57). Significant association was also detected to SLE patients (P-value = 8.29x10(-6), OR = 2.14, 95% CI = 1.52-3.00), and even stronger association was found when stratifying SLE patients by presence of discoid rash (P-value = 3.59x10(-8), OR = 3.76, 95% CI = 2.29-6.18). Significance: We propose ITGAM as a novel susceptibility gene for cutaneous DLE. The risk effect is independent of systemic involvement and has an even stronger genetic influence on the risk of DLE than of SLE.
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| 97. |
- Kangas, M., et al.
(författare)
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Comparison of real-life accidental falls in older people with experimental falls in middle-aged test subjects
- 2012
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Ingår i: Gait & Posture. - : Elsevier BV. - 0966-6362 .- 1879-2219. ; 35:3, s. 500-505
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Tidskriftsartikel (refereegranskat)abstract
- Falling is a common accident among older people. Automatic fall detectors are one method of improving security. However, in most cases, fall detectors are designed and tested with data from experimental falls in younger people. This study is one of the first to provide fall-related acceleration data obtained from real-life falls. Wireless sensors were used to collect acceleration data during a six-month test period in older people. Data from five events representing forward falls, a sideways fall, a backwards fall, and a fall out of bed were collected and compared with experimental falls performed by middle-aged test subjects. The signals from real-life falls had similar features to those from intentional falls. Real-life forward, sideways and backward falls all showed a pre impact phase and an impact phase that were in keeping with the model that was based on experimental falls. In addition, the fall out of bed had a similar acceleration profile as the experimental falls of the same type. However, there were differences in the parameters that were used for the detection of the fall phases. The beginning of the fall was detected in all of the real-life falls starting from a standing posture, whereas the high pre impact velocity was not. In some real-life falls, multiple impacts suggested protective actions. In conclusion, this study demonstrated similarities between real-life falls of older people and experimental falls of middle-aged subjects. However, some fall characteristics detected from experimental falls were not detectable in acceleration signals from corresponding heterogeneous real-life falls.
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| 98. |
- Kehr, J., et al.
(författare)
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Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats
- 2011
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Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 164:8, s. 1949-1958
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE The designer drug 1-(4-methylphenyl)-2-methylaminopropan-1-one (4-methylmethcathinone, mephedrone) is reported to possess psychostimulant, entactogenic and hallucinogenic effects. The purpose of this study was to examine the effects of acute administration of mephedrone on extracellular levels of dopamine (DA) and 5-HT in the nucleus accumbens of awake rats and compare these effects with those induced by 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and amphetamine. EXPERIMENTAL APPROACH Microdialysis sampling was performed while simultaneously recording locomotor activity in rats and the monoamines were determined by HPLC with electrochemical detection. KEY RESULTS Mephedrone (3 mg·kg−1 s.c.) and (+)-amphetamine (1 mg·kg−1 s.c.) caused rapid increases in extracellular DA levels of 496% and 412%, respectively, whereas MDMA (3 mg·kg−1 s.c.) showed only a moderate effect (235%). The corresponding 5-HT levels increased to 941% (mephedrone) and 911% (MDMA), but only to 165% following amphetamine. The calculated t1/2 values for elimination rate of mephedrone, MDMA and amphetamine-induced increases in extracellular DA levels were 25, 303 and 51 min, the corresponding t1/2 values for 5-HT were 26, 48 and 84 min, respectively. Locomotor activity was increased most by amphetamine, whereas both mephedrone and MDMA showed about three times lower and shorter-lasting effects. CONCLUSIONS AND IMPLICATIONS The neurochemical and functional properties of mephedrone resemble those of MDMA, but it also shows an amphetamine-like effect in that it evokes a rapid release and elimination of DA in the brain reward system, a feature that may contribute to its potent re-inforcing properties.
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| 99. |
- Kirkhus, Bente, et al.
(författare)
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Effects of similar intakes of marine n-3 fatty acids from enriched food products and fish oil on cardiovascular risk markers in healthy human subjects
- 2012
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Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 107:9, s. 1339-1349
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Tidskriftsartikel (refereegranskat)abstract
- There is convincing evidence that consumption of fish and fish oil rich in long-chain (LC) n-3 PUFA (n-3 LCPUFA), EPA (20 : 5n-3) and DHA (22 : 6n-3) reduce the risk of CHD. The aim of the present study was to investigate whether n-3 LCPUFA-enriched food products provide similar beneficial effects as fish oil with regard to incorporation into plasma lipids and effects on cardiovascular risk markers. A parallel 7-week intervention trial was performed where 159 healthy men and women were randomised to consume either 34 g fish pate (n 44), 500 ml fruit juice (n 38) or three capsules of concentrated fish oil (n 40), all contributing to a daily intake of approximately 1 g EPA and DHA. A fourth group did not receive any supplementation or food product and served as controls (n 37). Plasma fatty acid composition, serum lipids, and markers of inflammation and oxidative stress were measured. Compared with the control group, plasma n-3 LCPUFA and EPA: arachidonic acid ratio increased equally in all intervention groups. However, no significant changes in blood lipids and markers of inflammation and oxidative stress were observed. In conclusion, enriched fish pate and fruit juice represent suitable delivery systems for n-3 LCPUFA. However, although the dose given is known to reduce the risk of CVD, no significant changes were observed on cardiovascular risk markers in this healthy population.
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| 100. |
- Kivimäki, Mika, et al.
(författare)
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Associations of job strain and lifestyle risk factors with risk of coronary artery disease : a meta-analysis of individual participant data
- 2013
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Ingår i: CMJA. Canadian Medical Association Journal. Onlineutg. Med tittel. - : CMA Joule Inc.. - 0820-3946 .- 1488-2329. ; 185:9, s. 763-769
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is unclear whether a healthy lifestyle mitigates the adverse effects of job strain on coronary artery disease. We examined the associations of job strain and lifestyle risk factors with the risk of coronary artery disease.Methods: We pooled individual-level data from 7 cohort studies comprising 102 128 men and women who were free of existing coronary artery disease at baseline (1985–2000). Questionnaires were used to measure job strain (yes v. no) and 4 lifestyle risk factors: current smoking, physical inactivity, heavy drinking and obesity. We grouped participants into 3 lifestyle categories: healthy (no lifestyle risk factors), moderately unhealthy (1 risk factor) and unhealthy (2–4 risk factors). The primary outcome was incident coronary artery disease (defined as first nonfatal myocardial infarction or cardiac-related death).Results: There were 1086 incident events in 743 948 person-years at risk during a mean follow-up of 7.3 years. The risk of coronary artery disease among people who had an unhealthy lifestyle compared with those who had a healthy lifestyle (hazard ratio [HR] 2.55, 95% confidence interval [CI] 2.18–2.98; population attributable risk 26.4%) was higher than the risk among participants who had job strain compared with those who had no job strain (HR 1.25, 95% CI 1.06–1.47; population attributable risk 3.8%). The 10-year incidence of coronary artery disease among participants with job strain and a healthy lifestyle (14.7 per 1000) was 53% lower than the incidence among those with job strain and an unhealthy lifestyle (31.2 per 1000).Interpretation: The risk of coronary artery disease was highest among participants who reported job strain and an unhealthy lifestyle; those with job strain and a healthy lifestyle had half the rate of disease. A healthy lifestyle may substantially reduce disease risk among people with job strain.
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