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Sökning: WFRF:(Hjorth Maria)

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1.
  • Boij, Roland, et al. (författare)
  • Regulatory T-cell Subpopulations in Severe or Early-onset Preeclampsia
  • 2015
  • Ingår i: American Journal of Reproductive Immunology. - : WILEY-BLACKWELL. - 1046-7408 .- 1600-0897. ; 74:4, s. 368-378
  • Tidskriftsartikel (refereegranskat)abstract
    • Problem A deficiency in regulatory T (Treg) cells causing reduced immune regulatory capacity has been proposed in preeclampsia. Objective Utilizing recent advances in flow cytometry phenotyping, we aimed to assess whether a deficiency of Treg subpopulations occurs in preeclampsia. Method of study Six-color flow cytometry was used for Treg phenotyping in 18 preeclamptic women (one early-onset, one severe and 16 both), 20 women with normal pregnancy, and 20 non-pregnant controls. Results No differences were found in major Treg populations including CD127(low)CD25(+)/CD127(ow)FOXP3(+), resting (FOXP3(dim)CD45RA(+)), and activated (FOXP3(bright)CD45RA(-)) Treg cells, whereas preeclamptic women showed increased CTLA-4(+) and CCR4(+) proportions within resting/activated Treg populations. Corticosteroid treatment prior to blood sampling (n = 10) affected the distribution of Treg populations. Conclusions Although we found no major alterations in circulating Treg frequencies, differences in CTLA-4(+) and CCR4(+) frequencies suggest a migratory defect of Treg cells in preeclampsia. Corticosteroid treatment should be taken into account when evaluating Treg cells.
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2.
  • Carleo, Ilaria, et al. (författare)
  • The Multiplanet System TOI-421*
  • 2020
  • Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 160:3
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the discovery of a warm Neptune and a hot sub-Neptune transiting TOI-421 (BD-14 1137, TIC 94986319), a bright (V = 9.9) G9 dwarf star in a visual binary system observed by the Transiting Exoplanet Survey Satellite (TESS) space mission in Sectors 5 and 6. We performed ground-based follow-up observations-comprised of Las Cumbres Observatory Global Telescope transit photometry, NIRC2 adaptive optics imaging, and FIbre-fed Echelle Spectrograph, CORALIE, High Accuracy Radial velocity Planet Searcher, High Resolution echelle Spectrometer, and Planet Finder Spectrograph high-precision Doppler measurements-and confirmed the planetary nature of the 16 day transiting candidate announced by the TESS team. We discovered an additional radial velocity signal with a period of five days induced by the presence of a second planet in the system, which we also found to transit its host star. We found that the inner mini-Neptune, TOI-421 b, has an orbital period of P-b = 5.19672 +/- 0.00049 days, a mass of M-b = 7.17 +/- 0.66 M-circle plus, and a radius of R-b = R-circle plus, whereas the outer warm Neptune, TOI-421 c, has a period of P-c = 16.06819 +/- 0.00035 days, a mass of M-c = 16.42(-1.04)(+1.06)M(circle plus), a radius of R-c = 5.09(-0.15)(+0.16)R(circle plus), and a density of rho(c) = 0.685(-0.072)(+0.080) cm(-3). With its characteristics, the outer planet (rho(c) = 0.685(-0.0072)(+0.080) cm(-3)) is placed in the intriguing class of the super-puffy mini-Neptunes. TOI-421 b and TOI-421 c are found to be well-suited for atmospheric characterization. Our atmospheric simulations predict significant Ly alpha transit absorption, due to strong hydrogen escape in both planets, as well as the presence of detectable CH4 in the atmosphere of TOI-421 c if equilibrium chemistry is assumed.
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3.
  • Hedman Hjorth, Maria, et al. (författare)
  • Impaired CD4+ and CD8+ T cell phenotype and reduced chemokine secretion in recent-onset type 1 diabetic children
  • 2008
  • Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 153:3, s. 360-368
  • Tidskriftsartikel (refereegranskat)abstract
    • Although the role of the T cell-mediated autoimmune reaction in type 1 diabetes (T1D) is conclusive, studies including data from human circulating CD4+ and CD8+ lymphocytes subsets during the disease onset and posterior development are scarce. Further, chemokines and chemokine receptors are key players in the migration of pathogenic T cells into the islets of NOD mice developing T1D, but few studies have investigated these markers in human T1D patients. We studied the expression of T helper 1 (Th1) and Th2 associated chemokine receptors, and the two isoforms of CD45 leukocyte antigen on CD4+ and CD8+ lymphocytes from T1D and healthy children, as well as the secretion of chemokines in cell supernatants in peripheral blood mononuclear cells. Our results showed increased expression of CCR7 and CD45RA, and reduced CD45RO on CD8+ cells among recent-onset T1D patients. The percentages of CD4+ cells expressing CXC chemokine receptor 3 (CXCR3), CXCR6 and CCR5, and the secretion of interferon-γ-induced protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-1a and MIP-1β was lower among diabetics. Low expression of Th1-associated receptors and secretion of chemokines, together with an increased amount of CD8+ cells expressing CD45RA and CCR7 in T1D patients therefore might represent suboptimal Th function in T1D, leading to impaired T cytotoxic (Tc) responses or alternatively reflect a selective recruitment of Th1 cells into the pancreas.
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4.
  • Hedman Hjorth, Maria, 1978-, et al. (författare)
  • Nicotinamide reduces high secretion of IFN-γ in high-risk relatives even though it does not prevent type 1 diabetes
  • 2006
  • Ingår i: Journal of Interferon and Cytokine Research. - : Mary Ann Liebert Inc. - 1079-9907 .- 1557-7465. ; 26:4, s. 207-213
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 1 diabetes (T1D) is an autoimmune disease suggested to be of a T helper (Th)1-like origin. This study aimed to investigate the Th1-like and Th2-like profile in high-risk individuals during the prediabetic phase and the immunologic effect of treatment with nicotinamide. High-risk first-degree relatives of T1D patients participating in the European Nicotinamide Diabetes Intervention Trial (ENDIT) were treated with either nicotinamide or placebo. Peripheral blood mononuclear cells (PBMC) were obtained during the prediabetic phase and close to the onset of manifest T1D and from nondiabetic high-risk individuals. Using the sensitive enzyme-linked immunospot (ELISPOT) technique to distinguish Th1-like from Th2-like lymphocytes, secretion of interferon-γ (IFN-γ) and interleukin-4 (IL-4) was analyzed from PBMCs spontaneously and after in vitro stimulation with the diabetes-associated autoantigens, glutamic acid decarboxylase 65 (GAD65, protein and peptide, aa 247-279), recombinant tyrosine phosphatase (IA-2), and heat shock protein (HSP, aa 437-460). High-risk individuals showed high spontaneous as well as autoantigen-induced IFN-γ secretion. Secretion of IFN-γ and the IFN-γ/IL-4 ratio, induced by autoantigens, decreased in individuals developing T1D (p < 0.05), whereas nondiabetic individuals showed an increased IL-4 response (p < 0.05). Thus, a Th1-dominated cytokine profile observed in high-risk individuals inclined toward a diagnosis of diabetes. Nicotinamide caused decreased spontaneous (p = 0.05) and in vitro autoantigen-induced IFN-γ secretion (p < 0.05) and may play a role in immune regulation, even though it has not been shown to prevent T1D. © Mary Ann Liebert, Inc.
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5.
  • Hjorth, Maria, et al. (författare)
  • GAD-alum treatment induces GAD(65)-specific CD4(+)CD25(high)FOXP3(+) cells in type 1 diabetic patients
  • 2011
  • Ingår i: CLINICAL IMMUNOLOGY. - : Elsevier Science B.V., Amsterdam. - 1521-6616. ; 138:1, s. 117-126
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 1 diabetes results from autoimmune destruction of insulin producing pancreatic beta-cells. We have shown that treatment with alum-formulated glutamic acid decarboxylase 65 (GAD-alum) preserved residual insulin secretion and induced antigen-specific responses in children with recent onset type 1 diabetes. The aim of this study was to further investigate the immunomodulatory effect of GAD-alum, focusing on CD4(+)CD25(high) cells and their association to cytokine secretion. Samples obtained 21 and 30 months after the initial injection of GAD-alum or placebo were included in the present study. GAD(65)-stimulation enhanced the percentage of CD4(+)CD25(high)FOXP3(+) cells, but reduced the percentage of CD4(+)CD25(+) cells, in samples from the GAD-alum treated group. Further, the GAD(65)-induced secretion of IL-5, -10, and -13 correlated with the expression of CD4(+)CD25(high)FOXP3(+) cells, but inversely with CD4(+)CD25(+) cells. These new data suggest that GAD-alum treatment induced GAD(65)-specific T cells with regulatory features.
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7.
  • Hjorth, Maria, et al. (författare)
  • GAD-alum treatment induces GAD65-specific CD4+CD25highFOXP3+ cells in type 1 diabetic patients.
  • 2011
  • Ingår i: Clinical Immunology. - : Elsevier. - 1521-6616 .- 1521-7035. ; 138:1, s. 117-126
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 1 diabetes results from autoimmune destruction of insulin producing pancreatic β-cells. We have shown that treatment with alum-formulated glutamic acid decarboxylase 65 (GAD-alum) preserved residual insulin secretion and induced antigen-specific responses in children with recent onset type 1 diabetes. The aim of this study was to further investigate the immunomodulatory effect of GAD-alum, focusing on CD4+CD25high cells and their association to cytokine secretion. Samples obtained 21 and 30 months after the initial injection of GAD-alum or placebo were included in the present study. GAD65-stimulation enhanced the percentage of CD4+CD25highFOXP3+ cells, but reduced the percentage of CD4+CD25+ cells, in samples from the GAD-alum treated group. Further, the GAD65-induced secretion of IL-5, -10, and -13 correlated with the expression of CD4+CD25highFOXP3+ cells, but inversely with CD4+CD25+ cells. These new data suggest that GAD-alum treatment induced GAD65-specific T cells with regulatory features.
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8.
  • Hjorth, Maria, 1978- (författare)
  • Immunological profile and aspects of immunotherapy in type 1 diabetes
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Type 1 diabetes (T1D) is a chronic, autoimmune disease caused by a T cell mediated attack on the insulin producing pancreatic ß-cells. Even though reasonable quality of life can be acquired with modern insulin therapy, prevention of acute and late serious complications is facilitated by preservation of residual insulin secretion. Preventing β-cell destruction is therefore an important goal of T1D therapy. Characterisation of immunological changes in the course of T1D is essential for understanding the underlying pathogenic mechanisms and for evaluating the efficacy of therapeutic intervention. This thesis aimed to study the immune profile in individuals at increased risk of T1D and in patients diagnosed with the disease. In addition, the immunological effects of treatment with the B vitamin, Nicotinamide, and by antigen-specific immunotherapy using GAD65, have been studied in high-risk individuals and in T1D patients, respectively.We have found that individuals at high risk of T1D had an increased T helper (Th) 1 like immune profile, defined by high secretion of interferon (IFN) -γ. At the time of clinical onset of T1D, the Th1 dominance was diminished. We further demonstrate that children with newly diagnosed T1D had a suppressed Th1 like profile, detected by chemokine and chemokine receptor profile. This was accompanied by an induced population of CCR7+ and CD45RA+ naïve, CD8+cytotoxic T (Tc) cells and a reduced CD45RO+ memory Tc cell pool. It has previously been shown that oral Nicotinamide had no clinical effect in prevention of T1D. However, we found that the treatment was associated with a decreased secretion of IFN-γ. We have previously shown that subcutaneous injections with GAD-alum in T1D children induced a better preservation of endogenous insulin secretion compared with placebo. Here, we demonstrate that the treatment induced an early antigen-specific Th2 and regulatory immune profile. After a few months, and still after more than two years, the recall response to GAD65 was characterised by a broader range of cytokines. GAD-alum treatment also induced a GAD65-specific CD4+CD25highFOXP3+ cell population and reduced the levels of CD4+CD25+ cells. In conclusion, a Th1 like immune profile in pre-diabetic individuals indicates an imbalance of the immune system. At time of clinical onset, and in the period afterwards, reduction of the Th1 associated immune response could be an effect of a suppressed destructive process, selective recruitment of effector T cells to the pancreas or a defective immune regulation. The protective effect of GAD-alum in T1D children seems to be mediated by an early skewing of GAD65-induced responses towards a Th2 phenotype. Further, induction of GAD65-specific T cells with regulatory characteristics might be able to suppress autoreactive responses and inflammation in the pancreas.
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9.
  • Ludvigsson, Johnny, 1943-, et al. (författare)
  • GAD treatment and insulin secretion in recent-onset type 1 diabetes
  • 2008
  • Ingår i: New England Journal of Medicine. - Boston, Mass : Massachusetts medical society. - 0028-4793 .- 1533-4406. ; 359:18, s. 1909-1920
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The 65-kD isoform of glutamic acid decarboxylase (GAD) is a major autoantigen in patients with type 1 diabetes mellitus. This trial assessed the ability of alum-formulated GAD (GAD-alum) to reverse recent-onset type 1 diabetes in patients 10 to 18 years of age. Methods We randomly assigned 70 patients with type 1 diabetes who had fasting C-peptide levels above 0.1 nmol per liter (0.3 ng per milliliter) and GAD autoantibodies, recruited within 18 months after receiving the diagnosis of diabetes, to receive subcutaneous injections of 20 μg of GAD-alum (35 patients) or placebo (alum alone, 35 patients) on study days 1 and 30. At day 1 and months 3, 9, 15, 21, and 30, patients underwent a mixed-meal tolerance test to stimulate residual insulin secretion (measured as the C-peptide level). The effect of GAD-alum on the immune system was also studied. Results Insulin secretion gradually decreased in both study groups. The study treatment had no significant effect on change in fasting C-peptide level after 15 months (the primary end point). Fasting C-peptide levels declined from baseline levels significantly less over 30 months in the GAD-alum group than in the placebo group (−0.21 vs. −0.27 nmol per liter [−0.62 vs. −0.81 ng per milliliter], P = 0.045), as did stimulated secretion measured as the area under the curve (−0.72 vs. −1.02 nmol per liter per 2 hours [−2.20 vs. −3.08 ng per milliliter per 2 hours], P = 0.04). No protective effect was seen in patients treated 6 months or more after receiving the diagnosis. Adverse events appeared to be mild and similar in frequency between the two groups. The GAD-alum treatment induced a GAD-specific immune response. Conclusions GAD-alum may contribute to the preservation of residual insulin secretion in patients with recent-onset type 1 diabetes, although it did not change the insulin requirement. (ClinicalTrials.gov number, NCT00435981.)
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10.
  • Axelsson, Stina, et al. (författare)
  • Decreased GAD(65) -specific Th1/Tc1 phenotype in children with Type 1 diabetes treated with GAD-alum.
  • 2012
  • Ingår i: Diabetic Medicine. - : Wiley-Blackwell. - 0742-3071 .- 1464-5491. ; 29:10, s. 1272-1278
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim  The balance between T helper cell subsets is an important regulator of the immune system and is often examined after immune therapies. We aimed to study the immunomodulatory effect of glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) in children with Type 1 diabetes, focusing on chemokines and their receptors. Methods  Blood samples were collected from 70 children with Type 1 diabetes included in a phase II clinical trial with GAD-alum. Expression of CC chemokine receptor 5 (CCR5) and CCR4 was analysed on CD4+ and CD8+ lymphocytes after in vitro stimulation with GAD(65) using flow cytometry, and secretion of the chemokines CCL2, CCL3 and CCL4 was detected in peripheral blood mononuclear cell supernatants with Luminex. Results  Expression of Th1-associated CCR5 was down-regulated following antigen challenge, together with an increased CCR4/CCR5 ratio and CCL2 secretion in GAD-alum-treated patients, but not in the placebo group. Conclusion  Our results suggest that GAD-alum treatment has induced a favourable immune modulation associated with decreased Th1/Tc1 phenotypes upon antigen re-challenge, which may be of importance for regulating GAD(65) immunity. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.
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11.
  • Axelsson, Stina, et al. (författare)
  • Early induction of GAD(65)-reactive Th2 response in type 1 diabetic children treated with alum-formulated GAD(65)
  • 2010
  • Ingår i: Diabetes/Metabolism Research Reviews. - : John Wiley and Sons. - 1520-7552 .- 1520-7560. ; 26:7, s. 559-568
  • Tidskriftsartikel (refereegranskat)abstract
    • Background We have previously shown that two injections of 20 mu g alum-formulated glutamic acid decarboxylase 65 (GAD(65)) (GAD-alum; Diamyd (R)) in children with recent-onset type 1 diabetes lead to preservation of residual insulin secretion. In vitro cytokine production at the 15 months follow-up indicated immunomodulation. In the present study, we took advantage of peripheral blood mononuclear cells, cryopreserved during early follow-ups, to investigate whether the immunomodulatory effect of GAD-alum was apparent earlier after treatment, preceding the changes previously reported at 15 months.Methods Peripheral blood mononuclear cells from 70 type 1 diabetic children, randomly assigned GAD-alum (n = 35) or placebo (n = 35), that had been frozen at baseline (n = 27) and after 1 (n = 58), 3 (n = 67) and 9 (n = 66) months, were stimulated in vitro with GAD(65), tyrosine phosphatase-like protein IA-2 peptide, insulin peptide, GAD-alum, alum formulation or phytohaemagglutinin. Interleukin (IL)-5, -6, -10, -12, -13, -17, tumour necrosis factor and interferon-gamma were measured in cell supernatants and serum samples using Luminex. Expression of FOXP3 and transforming growth factor-beta was determined by real-time reverse transcription polymerase chain reaction.Results Already 1 month after the first injection, GAD(65)-induced IL-5 and IL-13 together with FOXP3 were enhanced in GAD-alum-treated patients compared to those with placebo. The in vitro response at 3 and 9 months was characterized by a broader range of cytokines in the treated group. Notably, only the T-helper 2-associated cytokines IL-5 and IL-13 together with FOXP3 increased continuously over time.Conclusions Treatment with GAD-alum in type 1 diabetic children induced an early T-helper 2 immune enhanced response to GAD(65), followed by a wider spectrum of cytokines at 3 and 9 months. Copyright (C) 2010 John Wiley & Sons, Ltd.
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12.
  • Axelsson, Stina, et al. (författare)
  • Long-Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes
  • 2011
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 6:12
  • Tidskriftsartikel (refereegranskat)abstract
    • A phase II clinical trial with glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D). We have performed a 4-year follow-up study of 59 of the original 70 patients to investigate long-term cellular and humoral immune responses after GAD-alum-treatment. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with GAD(65). Frequencies of naive, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD(65) autoantibody (GADA) levels. We here show that GAD-alum-treated patients display increased memory T-cell frequencies and prompt T-cell activation upon in vitro stimulation with GAD(65), but not with control antigens, compared with placebo subjects. GAD(65)-induced T-cell activation was accompanied by secretion of T helper (Th) 1, Th2 and T regulatory cytokines and by induction of T-cell inhibitory pathways. Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD(65) enzymatic activity. In conclusion, memory T- and B-cell responses persist 4 years after GAD-alum-treatment. In parallel to a GAD(65)-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD(65) immunity.
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14.
  • Bache, Iben, et al. (författare)
  • An excess of chromosome 1 breakpoints in male infertility.
  • 2004
  • Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 12:12, s. 993-1000
  • Tidskriftsartikel (refereegranskat)abstract
    • In a search for potential infertility loci, which might be revealed by clustering of chromosomal breakpoints, we compiled 464 infertile males with a balanced rearrangement from Mendelian Cytogenetics Network database (MCNdb) and compared their karyotypes with those of a Danish nation-wide cohort. We excluded Robertsonian translocations, rearrangements involving sex chromosomes and common variants. We identified 10 autosomal bands, five of which were on chromosome 1, with a large excess of breakpoints in the infertility group. Some of these could potentially harbour a male-specific infertility locus. However, a general excess of breakpoints almost everywhere on chromosome 1 was observed among the infertile males: 26.5 versus 14.5% in the cohort. This excess was observed both for translocation and inversion carriers, especially pericentric inversions, both for published and unpublished cases, and was significantly associated with azoospermia. The largest number of breakpoints was reported in 1q21; FISH mapping of four of these breakpoints revealed that they did not involve the same region at the molecular level. We suggest that chromosome 1 harbours a critical domain whose integrity is essential for male fertility.
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15.
  • Byrne, Julianne, et al. (författare)
  • The PanCareSurFup consortium : research and guidelines to improve lives for survivors of childhood cancer
  • 2018
  • Ingår i: European Journal of Cancer. - : ELSEVIER SCI LTD. - 0959-8049 .- 1879-0852. ; 103:Nov, s. 238-248
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Second malignant neoplasms and cardiotoxicity are among the most serious and frequent adverse health outcomes experienced by childhood and adolescent cancer survivors (CCSs) and contribute significantly to their increased risk of premature mortality. Owing to differences in health-care systems, language and culture across the continent, Europe has had limited success in establishing multi-country collaborations needed to assemble the numbers of survivors required to clarify the health issues arising after successful cancer treatment. PanCareSurFup (PCSF) is the first pan-European project to evaluate some of the serious long-term health risks faced by survivors. This article sets out the overall rationale, methods and preliminary results of PCSF. Methods: The PCSF consortium pooled data from 13 cancer registries and hospitals in 12 European countries to evaluate subsequent primary malignancies, cardiac disease and late mortality in survivors diagnosed between ages 0 and 20 years. In addition, PCSF integrated radiation dosimetry to sites of second malignancies and to the heart, developed evidence-based guidelines for long-term care and for transition services, and disseminated results to survivors and the public. Results: We identified 115,596 individuals diagnosed with cancer, of whom 83,333 were 5-year survivors and diagnosed from 1940 to 2011. This single data set forms the basis for cohort analyses of subsequent malignancies, cardiac disease and late mortality and case-control studies of subsequent malignancies and cardiac disease in 5-year survivors. Conclusions: PCSF delivered specific estimates of risk and comprehensive guidelines to help survivors and care-givers. The expected benefit is to provide every European CCS with improved access to care and better long-term health.
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17.
  • Costache, Madalina Elena, et al. (författare)
  • Higher- and lower-order personality traits and cluster subtypes in social anxiety disorder
  • 2020
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 15:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Social anxiety disorder (SAD) can come in different forms, presenting problems for diagnostic classification. Here, we examined personality traits in a large sample of patients (N = 265) diagnosed with SAD in comparison to healthy controls (N = 164) by use of the Revised NEO Personality Inventory (NEO-PI-R) and Karolinska Scales of Personality (KSP). In addition, we identified subtypes of SAD based on cluster analysis of the NEO-PI-R Big Five personality dimensions. Significant group differences in personality traits between patients and controls were noted on all Big Five dimensions except agreeableness. Group differences were further noted on most lower-order facets of NEO-PI-R, and nearly all KSP variables. A logistic regression analysis showed, however, that only neuroticism and extraversion remained significant independent predictors of patient/control group when controlling for the effects of the other Big Five dimensions. Also, only neuroticism and extraversion yielded large effect sizes when SAD patients were compared to Swedish normative data for the NEO-PI-R. A two-step cluster analysis resulted in three separate clusters labelled Prototypical (33%), Introvert-Conscientious (29%), and Instable-Open (38%) SAD. Individuals in the Prototypical cluster deviated most on the Big Five dimensions and they were at the most severe end in profile analyses of social anxiety, self-rated fear during public speaking, trait anxiety, and anxiety-related KSP variables. While additional studies are needed to determine if personality subtypes in SAD differ in etiological and treatment-related factors, the present results demonstrate considerable personality heterogeneity in socially anxious individuals, further underscoring that SAD is a multidimensional disorder.
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18.
  • Eriksdotter, Maria, et al. (författare)
  • Plasma Fatty Acid Profiles in Relation to Cognition and Gender in Alzheimer's Disease Patients During Oral Omega-3 Fatty Acid Supplementation : The OmegAD Study
  • 2015
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 48:3, s. 805-812
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: ω3 fatty acids (ω3 FAs) may slow the rate of decline in cognitive performance in mild forms of cognitive impairment and Alzheimer's disease (AD). However, the relationship between changes of plasma ω3 FA levels and cognitive performance, as well as effects of gender, are poorly known.OBJECTIVE: To study the effect of 6-month administration of DHA-rich ω3 FA supplementation on plasma FA profiles in patients with mild to moderate AD in relation to cognitive performance and gender. This investigation is part of the OmegAD Study.METHODS: 174 AD patients (74 ± 9 years) were randomized to a daily intake of 2.3 g ω3 FA or placebo for 6 months; subsequently all received the ω3 FA preparation for the next 6 months. Baseline as well as changes in plasma levels of the main ω3 FAs in 165 patients, while receiving ω3 FA supplementation for 6 months, were analyzed for association to cognitive performance (assessed by ADAS-cog and MMSE scores) as well as to gender.RESULTS: Preservation of cognitive functioning, assessed by ADAS-cog or its sub-items (but not MMSE) scores, was significantly associated to increasing plasma ω3 FA levels over time. Thus, the higher ω3 FA plasma levels rose, the lower was the rate of cognitive deterioration. This effect was not related to gender; since although females displayed higher ω3 FA plasma levels than did males after 6 months of supplementation, this difference disappeared when adjusted for body weight.CONCLUSIONS: Since our study suggests dose-response relationships between plasma levels of ω3 FA and preservation of cognition, future ω3 FA trials in patients with mild AD should consider exploring graded (and body weight adjusted) doses of ω3 FA.
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19.
  • Faxen-Irving, Gerd, et al. (författare)
  • Does Fatty Acid Composition in Subcutaneous Adipose Tissue Differ between Patients with Alzheimer's Disease and Cohabiting Proxies?
  • 2018
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 61:2, s. 515-519
  • Tidskriftsartikel (refereegranskat)abstract
    • Low tissue levels of the major marine ω3 fatty acids (FAs) DHA and EPA are found in Alzheimer's disease (AD). We investigated if healthy proxies to AD patients have higher levels of these ω3 FAs. We observed lower levels of EPA and DHA in subcutaneous adipose tissue biopsies from 64 AD patients compared with 16 cognitively healthy proxies. No significant difference was observed when pairwise comparisons were made between a subset of 16 AD patients and their co-habiting proxies. Larger studies are needed to replicate these findings and to determine if they could depend on FA intake or differences in metabolism.
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20.
  • Faxén-Irving, Gerd, et al. (författare)
  • Effects on transthyretin in plasma and cerebrospinal fluid by DHA-rich n - 3 fatty acid supplementation in patients with Alzheimer's disease : the OmegAD study
  • 2013
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 36:1, s. 1-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Transthyretin (TTR) binds amyloid-β (Aβ) and may reduce brain Aβ, a pathological feature in Alzheimer's disease (AD). N - 3 fatty acids (FA), docosahexaenoic (DHA), and eicosapentaenoic acid (EPA) may increase TTR transcription in rat hippocampus. We studied effects of n - 3 FA supplementation on TTR-levels in patients with AD. Outpatients were randomized to receive 1.7 g DHA and 0.6 g EPA (n - 3/n - 3 group) or placebo (placebo/n - 3 group) during 6 months. After 6 months, all patients received n - 3 FA for another 6 months. TTR and FA were measured in plasma in all subjects, whereas TTR in cerebrospinal fluid (CSF) was measured in a subgroup. The study was completed by 89 patients in the n - 3/n - 3 group (75 y, 57% w) and 85 in the placebo/n - 3 group (75 y, 46% w). Baseline plasma-TTR was within normal range in both groups. After 6 months, plasma-TTR decreased in the placebo/n - 3 group (p < 0.001 within and p < 0.015 between the groups). No changes were observed in CSF TTR. From 6 to 12 months when both groups were supplemented, plasma-TTR increased significantly in both groups. Repeated measures ANOVA indicated an increase in TTR over time (p = 0.04) in those receiving n - 3 FA for 12 months. By linear regression analyses, n - 3 FA treatment was independently associated with increased plasma-TTR at 6 months (β = -0.172, p = 0.028). Thus, n - 3 FA treatment appeared to increase plasma-TTR in patients with AD. Since TTR may influence Aβ deposition in the brain, the results warrant further exploration.
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21.
  • Freund-Levi, Yvonne, 1956-, et al. (författare)
  • Effects of omega-3 fatty acids on inflammatory markers in cerebrospinal fluid and plasma in Alzheimer's disease : the OmegAD study
  • 2009
  • Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger. - 1420-8008 .- 1421-9824. ; 27:5, s. 481-490
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: omega-3 fatty acids (omega-3 FAs) found in dietary fish or fish oils are anti-inflammatory agents that may influence Alzheimer's disease (AD).OBJECTIVE: To study the effects of dietary omega-3 FA supplementation on inflammatory markers in cerebrospinal fluid (CSF) and plasma from patients with mild to moderate AD.METHODS: Thirty-five patients (70.3 +/- 8.2 years) were randomized to a daily intake of 2.3 g omega-3 FAs or placebo for 6 months. The inflammatory markers interleukin (IL)-6, tumour necrosis factor-alpha and soluble interleukin-1 receptor type II (sIL-1RII) were analysed in CSF and plasma at baseline and at 6 months. The AD markers tau-protein, hyperphosphorylated tau-protein and beta-amyloid (Abeta(1-42)) were assessed in CSF. High-sensitivity C-reactive protein was assessed in plasma. A possible relation to the APOE genotype was investigated.RESULTS: There was no significant treatment effect of omega-3 FAs on inflammatory and AD biomarkers in CSF or on inflammatory markers in plasma, nor was there any relation with APOE. A significant correlation was observed at baseline between sIL-1RII and Abeta(1-42) levels in CSF.CONCLUSIONS: Treatment of AD patients with omega-3 FAs for 6 months did not influence inflammatory or biomarkers in CSF or plasma. The correlation between sIL-1RII and Abeta(1-42) may reflect the reciprocal interactions between IL-1 and Abeta peptides.
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22.
  • Freund-Levi, Yvonne, 1956-, et al. (författare)
  • Effects of supplementation with omega-3 fatty acids on oxidative stress and inflammation in patients with Alzheimer's disease : the OmegAD study
  • 2014
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 42:3, s. 823-831
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Oxidative stress and inflammation are two key mechanisms suggested to be involved in the pathogenesis of Alzheimer's disease (AD). Omega-3 fatty acids (ω-3 FAs) found in fish and fish oil have several biological properties that may be beneficial in AD. However, they may also auto-oxidize and induce in vivo lipid peroxidation.OBJECTIVE: The objective of this study was to evaluate systemic oxidative stress and inflammatory biomarkers following oral supplementation of dietary ω-3 FA.METHODS: Forty patients with moderate AD were randomized to receive 1.7 g DHA (22:6) and 0.6 g EPA (20:5) or placebo for 6 months. Urinary samples were collected before and after supplementation. The levels of the major F2-isoprostane, 8-iso-PGF2α, a consistent in vivo biomarker of oxidative stress, and 15-keto-dihydro-PGF2α, a major metabolite of PGF2α and biomarker of inflammatory response, were measured.RESULTS: F2-isoprostane in urine increased in the placebo group after 6 months, but there was no clear difference in treatment effect between supplemented and non-supplemented patients on the urinary levels of F2-isoprostanes and 15-keto-dihydro-PGF2α. At baseline, the levels of 15-keto-dihydro-PGF2α showed negative correlative relationships to ω-3 FAs, and a positive correlation to linoleic acid. 8-iso-PGF2α correlated negatively to the ω-6 FA arachidonic acid.CONCLUSION: The findings indicate that supplementation of ω-3 FAs to patients with AD for 6 months does not have a clear effect on free radical-mediated formation of F2-isoprostane or cyclooxygenase-mediated formation of prostaglandin F2α. The correlative relationships to FAs indicate a potential role of FAs in immunoregulation.
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23.
  • Gandolfi, Davide, et al. (författare)
  • The Transiting Multi-planet System HD 3167: A 5.7 M ⊕ Super-Earth and an 8.3 M ⊕ Mini-Neptune
  • 2017
  • Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 154:3, s. 123-
  • Tidskriftsartikel (refereegranskat)abstract
    • HD 3167 is a bright (V = 8.9 mag) K0 V star observed by NASA’s K2 space mission during its Campaign 8. It has recently been found to host two small transiting planets, namely, HD 3167b, an ultra-short-period (0.96 days) super-Earth, and HD 3167c, a mini-Neptune on a relatively long-period orbit (29.85 days). Here we present an intensive radial velocity (RV) follow-up of HD 3167 performed with the FIES@NOT, HARPS@ESO-3.6 m, and HARPS-N@TNG spectrographs. We revise the system parameters and determine radii, masses, and densities of the two transiting planets by combining the K2 photometry with our spectroscopic data. With a mass of 5.69 ± 0.44 M⊕, a radius of 1.574 ± 0.054 R⊕, and a mean density of {8.00}-0.98+1.10 g cm^-3, HD 3167b joins the small group of ultra-short-period planets known to have rocky terrestrial compositions. HD 3167c has a mass of 8.33-1.85+1.79 M⊕ and a radius of 2.74}-0.100+0.106 R⊕, yielding a mean density of 2.21-0.53+0.56 g cm^-3, indicative of a planet with a composition comprising a solid core surrounded by a thick atmospheric envelope. The rather large pressure scale height (∼350 km) and the brightness of the host star make HD 3167c an ideal target for atmospheric characterization via transmission spectroscopy across a broad range of wavelengths. We found evidence of additional signals in the RV measurements but the currently available data set does not allow us to draw any firm conclusions on the origin of the observed variation.
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24.
  • Giertz, Eric, 1949-, et al. (författare)
  • Svensk konsultsektor i ny belysning : Utvecklingstrender och dynamik
  • 2016
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Konsultsektorn är inte en bransch i vanlig mening. Den består av företag med likartad affärslogik som är verksamma i helt olika branscher. Den expanderar i takt med att kunderna väljer att upphandla konsulter som gör utredningar, projekterar byggen, utvecklar produkter och IT-system, konstruerar maskiner, utformar reklamkampanjer, patentansökningar och affärsavtal, genomför revisioner och tester av olika slag, sköter rekrytering, bokföring eller telefonintervjuer, utvecklar organisationsformer, interna rutiner och mycket mer.Denna rapport baseras på en unik kartläggning av konsultföretag i Sverige. Initialt skapades en bruttolista av alla företag med SNI-koder som kunde tänkas dölja kunskapsintensiva konsultföretag. I nästa steg inhämtades uppgifter, bland annat via företagens hemsidor, om alla aktiebolag i bruttolistan med minst fem anställda. Cirka en tredjedel av bolagen sorterades då bort. Återstående företag, som kunde klassificeras som konsultföretag, samlades i en databas och kategoriserades efter verksamhetens inriktning. Databasen som är grunden för vår analys omfattar 6 421 företag med minst fem anställda. De hade 212 753 heltidsekvivalenter sysselsatta på 10 075 arbetsställen i Sverige år 2012. Därutöver fanns en lång svans av små aktiebolag med 1-4 anställda. Små bolag med liten omsättning, som kan antas vara bolag för bisysslor, sorterades bort. Av 46 703 aktiebolag med 1-4 anställda återstod därefter 10 205. Dessa hade uppskattningsvis 35 212 heltidsekvivalenter sysselsatta år 2012. Totalt rör det sig således om cirka 250 000 anställda i konsultsektorns aktiebolag. Studien bygger på heltidsekvivalenter som mått på anställda. Därför är det betydligt fler fysiska personer som arbetar inom de inkluderade företagen – lågt räknat cirka 300 000.Sett över en längre tidsperiod har den totala sysselsättningen inom konsultsektorn ständigt ökat i Sverige. Under de senaste fyra decennierna har antalet yrkesverksamma ökat från knappt 100 000 till cirka 300 000, eller från knappt tre till drygt sex procent av den totala sysselsättningen. I föreliggande analys har vi delat in konsultföretagen efter den funktion de fyller i fem olika huvudinriktningar. Den största inriktningen, Konsultföretag inom organisation och ledning, som domineras av undergruppen IT inom administration och management, svarade för knappt 31 % av sysselsättningen. Konsultföretag inom extern funktionell expertis svarade för drygt 21 %, Bemanningsföretag för drygt 20 %, Konsultföretag inom objektrelaterad projektering för drygt 17 % och Konsultföretag inom FoU för drygt 10 %. Att konsultsektorn expanderar är knappast en modetrend. Det är snarare en konsekvens av att det i takt med ökad komplexitet blir svårt för kunderna att ha egen anställd personal inom alla viktiga kompetensområden.Konsultsektorn har generellt en stark koncentration till storstäder. Den finns visserligen representerad i nästan alla delar av vårt land men koncentrationen till i första hand Stockholmsområdet, men även Göteborg och Malmö, är påfallande hög. Företag i Storstockholm svarar för över 40 % av alla konsulter i Sverige. Det är inte bara i absoluta tal som Stockholm utmärker sig. När sysselsättningen i konsultföretag med minst fem anställda sätts i relation till antalet invånare i åldrarna 16-64 år, så har Stockholms län, med 6,3 %, mer än dubbelt så stor andel som andra län, utom Västra Götalands län med 4,1 %. Graden av koncentration till Stockholm och övriga storstäder varierar dock mellan olika inriktningar.Konsultsektorn som helhet kännetecknas av strukturomvandlingar, branschglidningar och stor dynamik. Det tar sig bland annat uttryck i fusioner, förvärv och börsintroduktioner. Inom några verksamhetsinriktningar har också större svenska bolag blivit uppköpta av utländska börsnoterade koncerner. Inom andra inriktningar, som domineras av partnerägda bolag, ingår svenska bolag numera i stora internationella nätverk av olika slag. Parallellt sker inom vissa inriktningar en ökad uppsplittring i små levebrödsbolag som knyts samman i nätverksorganisationer av olika slag. Även om de kvantitativa uppgifterna i vår databas baseras på situationen år 2012, så är alla strukturförändringar – i form av bland annat nedläggningar, fusioner och förvärv – som skett före den 1 januari 2016 beaktade i kvalitativa beskrivningar och exemplifieringar i rapporten.En del konsultföretag söker skapa strukturkapital och systematiskt dra kvalitets- och effektivitetsmässig nytta av att det – inte minst till följd av digitalisering – uppstår en slags stordriftsfördelar inom delar av konsultsektorn. En ambition i vår studie har varit att kartlägga vilka förutsättningar konsultföretag i Sverige har att bygga strukturkapital. Det är ju exempelvis stor skillnad mellan å ena sidan ett konsultföretag som mot timarvode hyr ut personal som sitter i kundernas lokaler och leds av kundernas personal och å andra sidan ett konsultföretag som mot ett fast arvode genomför ett väldefinierat projekt i eget kontor i Sverige och/eller utomlands. Under sommaren år 2015 lät vi sålunda genomföra intervjuer i konsultbolag med mer än cirka 20 anställda i Sverige. Frågorna fokuserade på var konsulterna utför sitt arbete, vem som leder dem operativt i uppdragen, eventuell export eller användning av offshoring, utnyttjande av underkonsulter, antal kunder per konsult, kundrelationer och debiteringsprinciper.Intervjuresultatet antyder att det i Sverige främst är Konsultföretag inom extern funktionell expertis som systematiskt bygger strukturkapital och söker effektivisera och kvalitetssäkra konsulternas arbete. De företag som debiterar fast pris har då även möjlighet att öka sina marginaler. Två huvudinriktningar med motsatt mönster är Konsultföretag inom FoU samt Bemanningsföretag. Båda dessa inriktningar domineras av företag som har utlokaliserade konsulter, vilka sitter ute hos kund och leds av kundernas personal. Varje konsult har dessutom endast ett fåtal olika uppdragsgivare per år. Undergruppen Bygg och anläggning inom huvudinriktningen Konsultföretag inom objektrelaterad projektering samt undergruppen IT inom administration och management i huvudinriktningen Konsultföretag inom organisation och ledning svarar tillsammans för drygt 40 % av alla anställda i konsultsektorn. De domineras av större företag som ingår i internationella koncerner. Vår bedömning är att dessa koncerner, trots sin storlek, bygger förhållandevis lite strukturkapital. Dessutom är timdebitering fortfarande helt dominerande.Sammanfattningsvis konstaterar vi att konsultsektorn är expansiv och att den spelar en betydelsefull roll för utvecklingen i näringslivet och i samhället som helhet. Sektorn är dynamisk och många konsultföretag står inför stora utmaningar. Det verkar finnas utrymme för exempelvis nya affärsmodeller, nya strategiska val och internationell expansion.
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25.
  • Govender, Melissa, et al. (författare)
  • T cell perturbations persist for at least 6 months following hospitalization for COVID-19
  • 2022
  • Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8(+) TEMRA and exhausted CD57(+) CD8(+) T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T cell activation were upregulated at inclusion, and in the case of CD69(+) CD4(+) T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis.
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26.
  • Grabow, Desiree, et al. (författare)
  • The PanCareSurFup cohort of 83,333 five-year survivors of childhood cancer : a cohort from 12 European countries
  • 2018
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 33:3, s. 335-349
  • Tidskriftsartikel (refereegranskat)abstract
    • Childhood cancer survivors face risks from a variety of late effects, including cardiac events, second cancers, and late mortality. The aim of the pan-European PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies (PanCareSurFup) Consortium was to collect data on incidence and risk factors for these late effects among childhood cancer survivors in Europe. This paper describes the methodology of the data collection for the overall PanCareSurFup cohort and the outcome-related cohorts. In PanCareSurFup 13 data providers from 12 countries delivered data to the data centre in Mainz. Data providers used a single variable list that covered all three outcomes. After validity and plausibility checks data was provided to the outcome-specific working groups. In total, we collected data on 115,596 patients diagnosed with cancer from 1940 to 2011, of whom 83,333 had survived 5 years or more. Due to the eligibility criteria and other requirements different numbers of survivors were eligible for the analysis of each of the outcomes. Thus, 1014 patients with at least one cardiac event were identified from a cohort of 39,152 5-year survivors; for second cancers 3995 survivors developed at least one second cancer from a cohort of 71,494 individuals, and from the late mortality cohort of 79,441 who had survived at least 5 years, 9247 died subsequently. Through the close cooperation of many European countries and the establishment of one central data collection and harmonising centre, the project succeeded in generating the largest cohort of children with cancer to date.
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27.
  • Heymer, Emma J., et al. (författare)
  • Cumulative Absolute Risk of Subsequent Colorectal Cancer After Abdominopelvic Radiotherapy Among Childhood Cancer Survivors : A PanCareSurFup Study
  • 2024
  • Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 42:3, s. 336-347
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE Childhood cancer survivors are at the risk of developing subsequent colorectal cancers (CRCs), but the absolute risks by treatment modality are uncertain. We quantified the absolute risks by radiotherapy treatment characteristics using clinically accessible data from a Pan-European wide case-control study nested within a large cohort of childhood cancer survivors: the PanCareSurFup Study. METHODS Odds ratios (ORs) from a case-control study comprising 143 CRC cases and 143 controls nested within a cohort of 69,460 survivors were calculated. These, together with standardized incidence ratios for CRC for this cohort and European general population CRC incidence rates and survivors' mortality rates, were used to estimate cumulative absolute risks (CARs) by attained age for different categories of radiation to the abdominopelvic area. RESULTS Overall, survivors treated with abdominopelvic radiotherapy treatment (ART) were three times more likely to develop a subsequent CRC than those who did not receive ART (OR, 3.1 [95% CI, 1.4 to 6.6]). For male survivors treated with ART, the CAR was 0.27% (95% CI, 0.17 to 0.59) by age 40 years, 1.08% (95% CI, 0.69 to 2.34) by age 50 years (0.27% expected in the general population), and 3.7% (95% CI, 2.36 to 7.80) by age 60 years (0.95% expected). For female survivors treated with ART, the CAR was 0.29% (95% CI, 0.18 to 0.62) by age 40 years, 1.03% (95% CI, 0.65 to 2.22) by age 50 years (0.27% expected), and 3.0% (95% CI, 1.91 to 6.37) by age 60 years (0.82% expected). CONCLUSION We demonstrated that by age 40 years survivors of childhood cancer treated with ART already have a similar risk of CRC as those age 50 years in the general population for whom population-based CRC screening begins in many countries. This information should be used in the development of survivorship guidelines for the risk stratification of survivors concerning CRC risk.
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28.
  • Heymer, Emma J., et al. (författare)
  • Risk of subsequent gliomas and meningiomas among 69,460 5-year survivors of childhood and adolescent cancer in Europe : the PanCareSurFup study
  • 2024
  • Ingår i: British Journal of Cancer. - 0007-0920. ; 130:6, s. 976-986
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort. Methods: Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940–2008), across Europe, standardized incidence ratios (SIRs) and cumulative incidence were calculated. Results: In total, 279 glioma and 761 meningioma were identified. CNS tumour (SIR: 16.2, 95% CI: 13.7, 19.2) and leukaemia (SIR: 11.2, 95% CI: 8.8, 14.2) survivors were at greatest risk of glioma. The SIR for CNS tumour survivors was still 4.3-fold after age 50 (95% CI: 1.9, 9.6), and for leukaemia survivors still 10.2-fold after age 40 (95% CI: 4.9, 21.4). Following cranial radiotherapy (CRT), the cumulative incidence of a glioma in CNS tumour survivors was 2.7%, 3.7% and 5.0% by ages 40, 50 and 60, respectively, whilst for leukaemia this was 1.2% and 1.7% by ages 40 and 50. The cumulative incidence of a meningioma after CRT in CNS tumour survivors doubled from 5.9% to 12.5% between ages 40 and 60, and in leukaemia survivors increased from 5.8% to 10.2% between ages 40 and 50. Discussion: Clinicians following up survivors should be aware that the substantial risks of meningioma and glioma following CRT are sustained beyond age 40 and be vigilant for symptoms.
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29.
  • Hjorth, Elin (författare)
  • Experiences of care and everyday life in a time of change for families in which a child has spinal muscular atrophy
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis focuses on children with severe spinal muscular atrophy (SMA) and their families. Although the disease is severe, and the families are faced with challenges in everyday life related to the progressive muscle weakness that SMA causes, knowledge of their experiences of the situation is limited. The overall purpose of this thesis was therefore to explore how families, with a child who has SMA, experience the care received and their everyday life.The thesis encompasses two projects: a two-nationwide survey with 95 bereaved and non-bereaved parents (response rate of 84%) and an ethnographical study with two families (17 interviews and participant observations at six occasions).The findings showed that parents were generally pleased with the care their children received. However, there were some shortcomings, especially that staff lacked knowledge about the diagnosis, leading the parents to feel that they themselves had to take initiatives for measurements and treatments (Paper II).Further, the parents reported deficiencies in coordination between care providers (Papers I–II). The parents emphasised the importance of having a good relationship with staff (Paper II), to find ways to cope with everyday life and get practical support in everyday activities, as well as social support in dealing with disease and grief (Paper III). With the new medicine for SMA, the families’narratives were rewritten, and the families were facing slow improvements; small events that made a big difference. Hope was negotiated and struggled with indifferent ways by different family members, but contributed to how they dealt with the disease and the outlook on the future (Paper IV).Many of the experiences described by the families can be useful for professionals in modifying their work to support these families in accordance with their needs.
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30.
  • Hjorth, Erik, et al. (författare)
  • Omega-3 fatty acids enhance phagocytosis of Alzheimer's disease-related amyloid-β42 by human microglia and decrease inflammatory markers
  • 2013
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 35:4, s. 697-713
  • Tidskriftsartikel (refereegranskat)abstract
    • The use of supplements with omega-3 (ω3) fatty acids (FAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is widespread due to proposed beneficial effects on the nervous and cardiovascular systems. Many effects of ω3 FAs are believed to be caused by down-regulation and resolution of inflammation. Alzheimer's disease (AD) is associated with inflammation mediated by microglia and astrocytes, and ω3 FAs have been proposed as potential treatments for AD. The focus of the present study is on the effects of DHA and EPA on microglial phagocytosis of the AD pathogen amyloid-β (Aβ), on secreted and cellular markers of immune activity, and on production of brain-derived neurotrophic factor (BDNF). Human CHME3 microglial cells were exposed to DHA or EPA, with or without the presence of Aβ42. Phagocytosis of Aβ42 was analyzed by flow cytometry in conjunction with immunocytochemistry using antibodies to cellular proteins. Secreted proteins were analyzed by ELISA. Both DHA and EPA were found to stimulate microglial phagocytosis of Aβ42. Phagocytosis of Aβ42 was performed by microglia with a predominance of M2 markers. EPA increased the levels of BDNF in the culture medium. The levels of TNF-α were decreased by DHA. Both DHA and EPA decreased the pro-inflammatory M1 markers CD40 and CD86, and DHA had a stimulatory effect on the anti-inflammatory M2 marker CD206. DHA and EPA can be beneficial in AD by enhancing removal of Aβ42, increasing neurotrophin production, decreasing pro-inflammatory cytokine production, and by inducing a shift in phenotype away from pro-inflammatory M1 activation.
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31.
  • Hjorth, Katrine, et al. (författare)
  • Estimating exponential scheduling preferences
  • 2015
  • Ingår i: Transportation Research Part B. - : Elsevier. - 0191-2615 .- 1879-2367. ; 81:1, s. 230-251
  • Tidskriftsartikel (refereegranskat)abstract
    • Different assumptions about travelers' scheduling preferences yield different measures of the cost of travel time variability. Only few forms of scheduling preferences provide non-trivial measures which are additive over links in transport networks where link travel times are arbitrarily distributed independent random variables. Assuming smooth preferences, this holds only for specifications with a constant marginal utility of time at the origin and an exponential or affine marginal utility of time at the destination. We apply a generalized version of this model to stated preference data of car drivers' route and mode choice under uncertain travel times. Our analysis exposes some important methodological issues related to complex non-linear scheduling models. One issue is identifying the point in time where the marginal utility of being at the destination becomes larger than the marginal utility of being at the origin. Another issue is that models with the exponential marginal utility formulation suffer from empirical identification problems. Though our results are not decisive, they partly support the constant-affine specification, in which the value of travel time variability is proportional to the variance of travel time.
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32.
  • Hjorth, Maria (författare)
  • Daily Experiences and Perceived Quality of Care for Patients with Liver Cirrhosis
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Aim and methods: This thesis aimed to study patients’ experiences with illness in their day-to-day lives and their perceived quality of care before and after implementing a 24-month adjunctive registered nurse-based outpatient intervention in liver cirrhosis. Qualitative data was used to explore patient perspectives on day-to-day life and healthcare experiences related to liver cirrhosis. The patient-perceived quality of care following the adjunctive registered nurse-based outpatient care was studied in a pragmatic, randomised controlled multicentre study, preceded by a study protocol.Results: Liver cirrhosis led to physical symptoms sometimes appearing rapidly. Fatigue, fear and social stigma affected daily life, resulting in cancelled activities and creating an unpredictable daily life situation. Patients with liver cirrhosis lacked adequate support to learn about the disease and manage it. They sought a trustworthy relationship with healthcare providers. When this was lacking, they felt neglected. After 12 months, the adjunctive registered nurse-based outpatient care revealed an improvement in patient-perceived quality of care. Enhancements were observed in 7 out of 22 questionnaire items regarding: patient participation, access to outpatient care, and feeling understood. However, these improvements were not sustained after 24 months.Conclusions: Fluctuating liver cirrhosis symptoms and constant worry significantly impact patients’ daily lives. Patients expressed a wish to be more involved in their healthcare and support in understanding and managing their illness. Structured registered nurse-based outpatient care for liver cirrhosis could complement physician-based care to meet patient desires for a more person-centred approach, continuity and care coordination. 
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33.
  • Hjorth, Maria, et al. (författare)
  • Feeling safe or falling through the cracks – Patients’ experiences of healthcare in cirrhosis illness: A qualitative study
  • 2023
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:4
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionPatients with cirrhosis have a long-lasting relationship with medical personnel. Hierarchy in the healthcare contacts and feeling stigmatised may affect the patient’s interactions with these care providers. Despite healthcare professionals’ awareness of patients’ increased self-care needs, patients report getting insufficient information and support. The patients’ expectations and experiences of interacting with healthcare professionals in cirrhosis care is hence a research area that needs further investigation.PurposeTo capture patients’ descriptions of healthcare experiences in relation to cirrhosis illness.Material and methodsData comprise semi-structured interviews (N = 18) and open-ended questionnaire responses (N = 86) of patients with cirrhosis. Braun and Clarke’s thematic analysis process was used, including both semantic and inductive elements. The study is reported following the COREQ guidelines.FindingsThe analysis resulted in two themes: 1) Struggle to be in a dialogue and 2) Being helped or harmed. Six sub-themes were identified concerning aspects of experiences within each theme during the analysis. These sub-themes included: ‘getting information’, ‘being involved’, ‘being perceived as a person’, ‘enduring care’, ‘feeling lost in the healthcare organisation’, and ‘not being taken care of’.ConclusionsPatients with cirrhosis express concerns regarding where to turn in the continuum of cirrhosis care. They emphasise the importance of being involved in the dialogue with the healthcare professional, to be perceived as a person with a unique need to be informed. The healthcare organisation and continuity of care are either viewed as confusing or as helping to shape a safe and trustful contact, which was an important difference in feeling helped or harmed. Hence, patients wished for improved collaboration with healthcare professionals and to receive increased information about their disease. Person-centred communication in nurse-led clinics may increase patient satisfaction and prevent patients from falling through the cracks.
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34.
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35.
  • Hjorth, Maria, et al. (författare)
  • Liver cirrhosis turns life into an unpredictable roller-coaster : A qualitative interview study.
  • 2020
  • Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 29, s. 4532-4543
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: To explore how persons living with liver cirrhosis experience day-to-day life.BACKGROUND: Liver cirrhosis is the sixth most common cause of death among adults in Western countries. Persons with advanced liver cirrhosis report poor quality of life, in comparison with other chronic diseases. However, knowledge regarding day-to-day life during earlier stages of the disease is lacking. In other chronic diseases, the suffering process is well explored, while in liver cirrhosis suffering is insufficiently investigated.DESIGN: An exploratory study, with a qualitative inductive interview approach.METHODS: A purposive maximum variation sample of 20 informants with liver cirrhosis aged 25-71, from two gastroenterology outpatient clinics in mid-Sweden, were interviewed from September 2016 to October 2017. Interview data were analysed inductively with qualitative content analysis. Reporting followed the COREQ guidelines.RESULTS: The experiences of day-to-day life living with liver cirrhosis comprised four sub-themes. Living with liver cirrhosis implied varying levels of deterioration, the most apparent being exhaustion or tiredness. The informants had to find ways of adapting to a new life situation. The insecurity of future health evoked existential reflections such as feeling emotionally and existentially distressed. Shame and guilt were reasons for feeling stigmatised. These sub-themes emerged into one overarching theme of meaning: life turns into an unpredictable roller-coaster. This is based on experiences of liver cirrhosis as an unpredictable disease with fluctuating symptoms, worries and disease progression.CONCLUSION: Living with cirrhosis implies an unpredictable condition with a progressive, stigmatising disease. The fluctuating symptoms and deep concerns about future life pose an increased personal suffering.RELEVANCE TO CLINICAL PRACTICE: Within healthcare, knowledge of the person's experience is vital to enable and fulfil the person's healthcare needs. Clinical registered nurses need a person-centred approach to strengthen their patients to cope with their new life situation.
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36.
  • Hjorth, Maria, et al. (författare)
  • Nurse-led clinic for patients with liver cirrhosis-effects on health-related quality of life : study protocol of a pragmatic multicentre randomised controlled trial
  • 2018
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 8:10
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Liver cirrhosis affects health-related quality of life (HRQoL) even in its early stages. Morbidity is especially high when the disease decompensates and self-care actions become essential. Nurse involvement in secondary prevention in other chronic diseases has contributed to better symptom control, less need of inpatient care and improved HRQoL. In order to evaluate the impact of nurse involvement in the follow-up of patients with liver cirrhosis, we decided to compare structured nurse-led clinics, inspired by Dorothea Orem's nursing theory and motivational strategies, with a group of patients receiving standard care. The primary outcome is HRQoL and the secondary outcomes are quality of care, visits to outpatient clinics or hospitals, disease progress and health literacy.METHODS AND ANALYSIS: This is a pragmatic, multicentre randomised controlled study conducted at six Swedish hepatology departments. Eligible patients are adults with diagnosed cirrhosis of the liver (n=500). Participants are randomised into either an intervention with nurse-led follow-up group or into a standard of care group. Recruitment started in November 2016 and is expected to proceed until 2020. Primary outcomes are physical and mental HRQoL measured by RAND-36 at enrolment, after 1 and 2 years.ETHICS AND DISSEMINATION: The study is ethically approved by the Regional Ethical Review Board in Uppsala. The results shall be disseminated in international conferences and peer-reviewed articles.TRIAL REGISTRATION NUMBER: NCT02957253; Pre-results.
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37.
  • Hjorth, Maria, et al. (författare)
  • Patient perceived quality of cirrhosis care – adjunctive nurse-based care versus standard medical care : a pragmatic multicentre randomised controlled study
  • 2024
  • Ingår i: BMC Nursing. - : BioMed Central (BMC). - 1472-6955. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundCirrhosis treatment implies prevention and alleviation of serious disease events. Healthcare providers may, however, fail to meet patients’ expectations of collaboration and specific needs of information and support. Individualised nursing care could meet patients’ needs. The aim was thus to measure patient-perceived quality of care after adjunctive registered nurse-based intervention Quality Liver Nursing Care Model (QLiNCaM) compared with standard medical care.MethodsThis pragmatic multicentre study consecutively randomised patients to either adjunctive registered nurse-based care, or standard medical care for 24 months (ClinicalTrials.gov NCT02957253). Patients were allocated to either group at an equal ratio, at six Swedish outpatient clinics during 2016–2022. Using the questionnaire ‘Quality of care from the patient’s perspective’, patients rated their perceived lack of quality for the adjunctive registered nurse-based intervention compared with the control group at 12 and 24 months, respectively.ResultsIn total, 167 patients were recruited. Seven out of 22 items in the questionnaire supported the finding that ‘lacking quality’ decreased with adjunctive registered nurse-based care (p < 0.05) at 12 months follow-up; however, these differences could not be established at 24 months.ConclusionAdditional structured registered nurse-based visits in the cirrhosis outpatient team provided support for improved patient-perceived quality of care during the first 12 months. Registered nurses increase patient involvement and present easy access to cirrhosis outpatient care. Patients express appreciation for personalised information. This study reinforces registered nurses’ role in the outpatient cirrhosis team, optimising patient care in compensated and decompensated cirrhosis.
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38.
  • Hjorth, Maria, et al. (författare)
  • Treatment effects of fingolimod in multiple sclerosis: Selective changes in peripheral blood lymphocyte subsets
  • 2020
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 15:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Treatment with fingolimod reduces inflammation in multiple sclerosis (MS) by inhibiting lymphocyte egress from lymph nodes. We aimed to map, in detail, the alterations in peripheral blood lymphocyte subpopulations in relation to clinical outcome in MS patients treated with fingolimod. Methods Paired blood samples from relapsing-remitting MS patients (n = 19) were collected before and after one year of treatment with fingolimod (0.5 mg/day). Absolute counts and relative proportions of a broad set of T- B- and NK-cell subsets were analyzed by flow cytometry. Blood samples from 18 healthy controls were used for baseline comparisons. Results Treatment with fingolimod markedly decreased the absolute numbers of all major lymphocyte subsets, except for NK cells. The reduction was most pronounced within the T helper (Th) and B cell populations (p < 0.001). By phenotyping differentiation status of T cells, dramatic reductions within the naive and central memory (CM) cell populations were found (p < 0.001), while a less pronounced reduction was observed among effector memory (EM) cells (p < 0.001). The numbers of regulatory T cells (Tregs) were also decreased (p < 0.001), but to a lesser extent than other T cell populations, resulting in a relative preservation of Tregs with a memory phenotype (p = 0.002). Conclusions Our results confirm that fingolimod therapy markedly reduces lymphocyte counts in peripheral blood of MS patients. Subgroup analysis of T cells showed that naive and CM Th cells were the most profoundly affected and that memory Tregs were relatively preserved.
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39.
  • Irving, Gerd Faxén, et al. (författare)
  • Omega-3 fatty acid supplementation effects on weight and appetite in patients with Alzheimer's disease : the omega-3 Alzheimer's disease study
  • 2009
  • Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 57:1, s. 11-17
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To study the effects of omega (Omega)-3 fatty acid (FA) supplements on weight and appetite in patients with mild to moderate Alzheimer's disease (AD) in relation to inflammatory biomarkers and apolipoprotein E epsilon4 (APOEepsilon4). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Specialist memory clinics in the Stockholm catchment area. PARTICIPANTS: Two hundred four patients (aged 73+/-9, 52% women) with mild to moderate AD. INTERVENTION: Patients with AD received 1.7 g of docosahexaenoic acid (DHA) and 0.6 g of eicosapentaenoic acid (EPA) (Omega-3/Omega-3 group; n=89, aged 73+/-9, 57% women) or placebo 0.6 g of linoleic acid per day (placebo/Omega-3 group; n=85, aged 73+/-9, 46% women) for 6 months. After 6 months, all patients received DHA and EPA for another 6 months. MEASUREMENTS: Anthropometry, biochemical nutritional and inflammatory markers, and appetite assessed by caregiver. RESULTS: Mean weight and body mass index (kg/m(2)) at baseline were 70.0+/-11.8 kg and 24.3+/-3.0 kg/m(2), respectively. At 6- and 12-month follow-up, weight had increased 0.7+/-2.5 kg (P=.02) and 1.4+/-2.9 kg (P<.001) in the Omega-3/Omega-3 group. In the placebo group, weight was unchanged at 6 months but had increased (P=.01) at 12 months follow-up after Omega-3 supplementation was initiated. Appetite improved in the Omega-3/Omega-3 group over the treatment period (P=.01). In logistic regression analyses, not carrying the APOEepsilon4 allele and high plasma DHA concentrations were independently related to weight gain in the combined group of patients at 6 months follow-up. CONCLUSION: A DHA-enriched Omega-3 FA supplement may positively affect weight and appetite in patients with mild to moderate AD. Not carrying the APOEepsilon4 allele and high DHA were independently associated with weight gain.
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40.
  • Jankovic, Momcilo, et al. (författare)
  • Long-term survivors of childhood cancer : cure and care—the Erice Statement (2006) revised after 10 years (2016)
  • 2018
  • Ingår i: Journal of Cancer Survivorship. - : Springer Science and Business Media LLC. - 1932-2259 .- 1932-2267. ; 12:5, s. 647-650
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The number of persons who have successfully completed treatment for a cancer diagnosed during childhood and who have entered adulthood is increasing over time, and former patients will become aging citizens. Methods: Ten years ago, an expert panel met in Erice, Italy, to produce a set of principles concerning the cure and care of survivors of childhood and adolescent cancer. The result was the Erice Statement (Haupt et al. Eur J Cancer 43(12):1778–80, 2007) that was translated into nine languages. Ten years on, it was timely to review, and possibly revise, the Erice Statement in view of the changes in paediatric oncology and the number and results of international follow-up studies conducted during the intervening years. Results: The long-term goal of the cure and care of a child with cancer is that he/she becomes a resilient and autonomous adult with optimal health-related quality of life, accepted in society at the same level as his/her age peers. “Cure” refers to cure from the original cancer, regardless of any potential for, or presence of, remaining disabilities or side effects of treatment. The care of a child with cancer should include complete and honest information for parents and the child. Conclusions and implication for cancer survivors: Some members of the previous expert panel, as well as new invited experts, met again in Erice to review the Erice Statement, producing a revised version including update and integration of each of the ten points. In addition, a declaration has been prepared, by the Childhood Cancer International Survivors Network in Dublin on October 2016 (see Annex 1).
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41.
  • Jernerén, Fredrik, et al. (författare)
  • Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer's Disease : The OmegAD Study
  • 2019
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 69:1, s. 189-197
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Trials of supplementation with omega-3 fatty acids (omega 3-FAs) in patients with mild cognitive impairment or Alzheimer's disease (AD) have produced inconsistent effects on cognitive decline. There is evidence of an interaction between B vitamin status and omega 3-FAs in relation to brain atrophy and cognitive decline.Objective: We investigated whether baseline levels of plasma total homocysteine (tHcy), a marker of B vitamin status, modify the effects of omega 3-FAs supplementation on cognitive performance in moderate AD.Methods: This post hoc analysis of the OmegAD trial included 171 community-based patients with AD (MMSE >= 15): 88 patients received daily doses of 1.7 g docosahexaenoic acid and 0.6 g eicosapentaenoic acid for 6 months. Treatment outcome on cognition was analyzed according to baseline levels of tHcy using a general linear model and ANCOVA.Results: We found significant interactions between omega 3-FA supplementation and tHcy on cognition and clinical stage assessed by MMSE (p = 0.040), global CDR (p = 0.059), and CDRsob (p = 0.023), but not on ADAS-cog (p = 0.649). In patients with tHcy levels <11.7 mu mol/L, omega 3-FA supplementation improved cognitive performance as measured by MMSE (+7.1%, 95% CI: 0.59 to 13.7%, p = 0.033) and clinical status as measured by CDRsob (-22.3%, 95% CI: -5.8 to -38.7%, p = 0.009) compared with placebo.Conclusion: The effect of omega 3-FA supplementation on MMSE and CDR appears to be influenced by baseline tHcy, suggesting that adequate B vitamin status is required to obtain beneficial effects of omega 3-FA on cognition.
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42.
  • Karimi, Mohsen, et al. (författare)
  • DHA-rich n-3 fatty acid supplementation decreases DNA methylation in blood leukocytes : the OmegAD study
  • 2017
  • Ingår i: American Journal of Clinical Nutrition. - : HighWire Press. - 0002-9165 .- 1938-3207. ; 106:4, s. 1157-1165
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Dietary fish oils, rich in long-chain n-3 (ω-3) fatty acids (FAs) [e.g., docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3)], modulate inflammatory reactions through various mechanisms, including gene expression, which is measured as messenger RNA concentration. However, the effects of long-term treatment of humans with DHA and EPA on various epigenetic factors-such as DNA methylation, which controls messenger RNA generation-are poorly described.Objective: We wanted to determine the effects of 6 mo of dietary supplementation with an n-3 FA preparation rich in DHA on global DNA methylation of peripheral blood leukocytes (PBLs) and the relation to plasma EPA and DHA concentrations in Alzheimer disease (AD) patients.Design: In the present study, DNA methylation in four 5'-cytosine-phosphate-guanine-3' (CpG) sites of long interspersed nuclear element-1 repetitive sequences was assessed in a group of 63 patients (30 given the n-3 FA preparation and 33 given placebo) as an estimation of the global DNA methylation in blood cells. Patients originated from the randomized, double-blind, placebo-controlled OmegAD study, in which 174 AD patients received either 1.7 g DHA and 0.6 g EPA (the n-3 FA group) or placebo daily for 6 mo.Results: At 6 mo, the n-3 FA group displayed marked increases in DHA and EPA plasma concentrations (2.6- and 3.5-fold), as well as decreased methylation in 2 out of 4 CpG sites (P < 0.05 for all), respectively. This hypomethylation in CpG2 and CpG4 sites showed a reverse correlation to changes in plasma EPA concentration (r = -0.25, P = 0.045; and r = -0.26, P = 0.041, respectively), but not to changes in plasma DHA concentration, and were not related to apolipoprotein E-4 allele frequency.Conclusion: Supplementation with n-3 FA for 6 mo was associated with global DNA hypomethylation in PBLs. Our data may be of importance in measuring various effects of marine oils, including gene expression, in patients with AD and in other patients taking n-3 FA supplements. This trial was registered at clinicaltrials.gov as NCT00211159.
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43.
  • Lam, Kristine W. F., et al. (författare)
  • It Takes Two Planets in Resonance to Tango around K2-146
  • 2020
  • Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 159:3
  • Tidskriftsartikel (refereegranskat)abstract
    • K2-146 is a cool, 0.358M dwarf that was found to host a mini-Neptune with a 2.67 day period. The planet exhibited strong transit timing variations (TTVs) of greater than 30 minutes, indicative of the presence of an additional object in the system. Here we report the discovery of the previously undetected outer planet in the system, K2-146 c, using additional photometric data. K2-146 c was found to have a grazing transit geometry and a 3.97 day period. The outer planet was only significantly detected in the latter K2 campaigns presumably because of precession of its orbital plane. The TTVs of K2-146 b and c were measured using observations spanning a baseline of almost 1200 days. We found strong anti -correlation in the TTVs, suggesting the two planets are gravitationally interacting. Our TTV and transit model analyses revealed that K2-146 b has a radius of 2.25 0.10 Re and a mass of 5.6 0.7 Me, whereas K2-146 c has a radius of 2.591 Re and a mass of 7.1 0.9 Me. The inner and outer planets likely have moderate eccentricities of e = 0.14 0.07 and 0.16 0.07, respectively. Long-term numerical integrations of the two -planet orbital solution show that it can be dynamically stable for at least 2 Myr. We show that the resonance angles of the planet pair are librating, which may be an indication that K2-146 b and c are in a 3:2 mean motion resonance. The orbital architecture of the system points to a possible convergent migration origin.
  •  
44.
  • Landberg, Niklas, et al. (författare)
  • CD36 defines primitive chronic myeloid leukemia cells less responsive to imatinib but vulnerable to antibody-based therapeutic targeting
  • 2018
  • Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 103:3, s. 447-455
  • Tidskriftsartikel (refereegranskat)abstract
    • Tyrosine kinase inhibitors (TKIs) are highly effective for the treatment of chronic myeloid leukemia (CML), but very few patients are cured. The major drawbacks regarding TKIs are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon drug cessation. Herein, we performed ribonucleic acid sequencing of flow-sorted primitive (CD34+CD38low) and progenitor (CD34+CD38+) chronic phase CML cells, and identified transcriptional upregulation of 32 cell surface molecules relative to corresponding normal bone marrow cells. Focusing on novel markers with increased expression on primitive CML cells, we confirmed upregulation of the scavenger receptor CD36 and the leptin receptor by flow cytometry. We also delineate a subpopulation of primitive CML cells expressing CD36 that is less sensitive to imatinib treatment. Using CD36 targeting antibodies, we show that the CD36 positive cells can be targeted and killed by antibody-dependent cellular cytotoxicity. In summary, CD36 defines a subpopulation of primitive CML cells with decreased imatinib sensitivity that can be effectively targeted and killed using an anti-CD36 antibody.
  •  
45.
  • Levan, Andrew J., et al. (författare)
  • A long-duration gamma-ray burst of dynamical origin from the nucleus of an ancient galaxy
  • 2023
  • Ingår i: Nature Astronomy. - 2397-3366. ; 7:8, s. 976-985
  • Tidskriftsartikel (refereegranskat)abstract
    • The majority of long-duration (>2 s) gamma-ray bursts (GRBs) arise from the collapse of massive stars, with a small proportion created from the merger of compact objects. Most of these systems form via standard stellar evolution pathways. However, a fraction of GRBs may result from dynamical interactions in dense environments. These channels could also contribute substantially to the samples of compact object mergers detected as gravitational wave sources. Here we report the case of GRB 191019A, a long GRB (a duration of T90 = 64.4 ± 4.5 s), which we pinpoint close (⪅100 pc projected) to the nucleus of an ancient (>1 Gyr old) host galaxy at z = 0.248. The lack of evidence for star formation and deep limits on any supernova emission disfavour a massive star origin. The most likely route for progenitor formation is via dynamical interactions in the dense nucleus of the host. The progenitor, in this case, could be a compact object merger. These may form in dense nuclear clusters or originate in a gaseous disc around the supermassive black hole. Identifying, to the best of our knowledge, a first example of a dynamically produced GRB demonstrates the role that such bursts may have in probing dense environments and constraining dynamical fractions in gravitational wave populations.
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46.
  • Licht, Sofie de Fine, et al. (författare)
  • Temporal changes in the probability of live birth among female survivors of childhood cancer : A population-based Adult Life After Childhood Cancer in Scandinavia (ALiCCS) study in five nordic countries
  • 2021
  • Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 127:20, s. 3881-3892
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: During the past 4 decades, there has been a growing focus on preserving the fertility of patients with childhood cancer; however, no large studies have been conducted of live births across treatment decades during this period. Therefore, the authors estimated the potential birth deficit in female childhood cancer survivors and the probability of live births. METHODS: In total, 8886 women were identified in the 5 Nordic cancer registries in whom a childhood cancer had been diagnosed during 1954 through 2006. A population comparison cohort of 62,903 women was randomly selected from the central population registries matched by age and country. All women were followed for live births recorded in medical birth registries. The cumulative probability and the risk ratio (RR) with 95% confidence intervals (CIs) of a live birth were calculated by maternal age across treatment decades. RESULTS: The probability of a live birth increased with treatment decade, and, at age 30 years, the rate for survivors most recently diagnosed was close to the rate among the general population (1954-1969: RR, 0.65 [95% CI, 0.54-0.78]; 1970s: RR, 0.67 [95% CI, 0.60-0.74]; 1980s: RR, 0.69 [95% CI, 0.64-0.74]; 1990s: RR, 0.91 [95% CI, 0.87-0.95]; 2000s: RR, 0.94 [95% CI, 0.91-0.97]). CONCLUSIONS: Female childhood cancer survivors had a lower probability of a live birth than women in the general population, although, in survivors diagnosed after 1989, the probability was close to that of the general population. Because the pattern of live births differs by cancer type, continuous efforts must be made to preserve fertility, counsel survivors, and refer them rapidly to fertility treatment if necessary. LAY SUMMARY: The purpose of this study was to compare the probability of giving birth to a liveborn child in female survivors of childhood cancer with that of women in the general population. Survivors of childhood cancer had a lower probability of live births than women in the general population, although survivors diagnosed after 1989 had a probability close to that of the general population. Continuing focus on how to preserve the potential for fertility among female patients with childhood cancer during treatment is important to increase their chances of having a child.
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47.
  • Ludvigsson, Johnny, et al. (författare)
  • Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial
  • 2011
  • Ingår i: DIABETOLOGIA. - : Springer Science Business Media. - 0012-186X .- 1432-0428. ; 54:3, s. 634-640
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to investigate the safety and efficacy of alum formulated glutamic acid decarboxylase GAD(65) (GAD-alum) treatment of children and adolescents with type 1 diabetes after 4 years of follow-up. Seventy children and adolescents aged 10-18 years with recent onset type 1 diabetes participated in a phase II, double-blind, randomised placebo-controlled clinical trial. Patients identified as possible participants attended one of eight clinics in Sweden to receive information about the study and for an eligibility check, including a medical history. Participants were randomised to one of the two treatment groups and received either a subcutaneous injection of 20 mu g of GAD-alum or placebo at baseline and 1 month later. The study was blinded to participants and investigators until month 30. The study was unblinded at 15 months to the sponsor and statistician in order to evaluate the data. At follow-up after 30 months there was a significant preservation of residual insulin secretion, as measured by C-peptide, in the group receiving GAD-alum compared with placebo. This was particularly evident in patients with andlt; 6 months disease duration at baseline. There were no treatment-related serious adverse events. We have now followed these patients for 4 years. Overall, 59 patients, 29 who had been treated with GAD-alum and 30 who had received placebo, gave their informed consent. One patient in each treatment group experienced an episode of keto-acidosis between months 30 and 48. There were no treatment-related adverse events. The primary efficacy endpoint was the change in fasting C-peptide concentration from baseline to 15 months after the prime injection for all participants per protocol set. In the GAD-alum group fasting C-peptide was 0.332 +/- 0.032 nmol/l at day 1 and 0.215 +/- 0.031 nmol/l at month 15. The corresponding figures for the placebo group were 0.354 +/- 0.039 and 0.184 +/- 0.033 nmol/l, respectively. The decline in fasting C-peptide levels between day 1 and month 1, was smaller in the GAD-alum group than the placebo group. The difference between the treatment groups was not statistically significant. In those patients who were treated within 6 months of diabetes diagnosis, fasting C-peptide had decreased significantly less in the GAD-alum group than in the placebo-treated group after 4 years. Four years after treatment with GAD-alum, children and adolescents with recent-onset type 1 diabetes continue to show no adverse events and possibly to show clinically relevant preservation of C-peptide. ClinicalTrials.gov NCT00435981 The study was funded by The Swedish Research Council K2008-55X-20652-01-3, Barndiabetesfonden (The Swedish Child Diabetes Foundation), the Research Council of Southeast Sweden, and an unrestricted grant from Diamyd Medical AB.
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48.
  • Löfgren, Orvar, et al. (författare)
  • Drömmen om den perfekta regionen
  • 2002
  • Ingår i: Come in - go out : det 10. billede : et workshopprojekt med Robert Wilson på Kunstakademiets Arkitektskole, København 2002. - 8775140721 ; , s. 7-18
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
  •  
49.
  • Mellqvist, Ulf-Henrik, et al. (författare)
  • Cyclophosphamide plus dexamethasone is an efficient initial treatment before high-dose melphalan and autologous stem cell transplantation in patients with newly diagnosed multiple myeloma - Results of a randomized comparison with vincristine, doxorubicin
  • 2008
  • Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 112:1, s. 129-135
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND. Today, intensive therapy that includes high-close melphalan with autologous stein cell transplantation (ASCT) is considered standard therapy in younger patients with newly diagnosed myeloma. When the current trial was initiated, combined vincristine, doxorubicin, and dexamethasone (VAD) was the most commonly used induction therapy before ASCT and yielded rapid major responses without interfering with stein cell harvest. However, the administration of VAD demands a central venous access, and well-described toxicities are associated with the therapy. This randomized trial, which was initiated in 2001 by the Nordic Myeloma Study Group, was an attempt to bring a larger portion of patients to ASCT more quickly. METHODS. Patients were randomized to receive either 3 cycles of VAD or 2 courses of cyclophosphamide plus dexamethasone (Cy-Dex) (cyclophosphamide at a dose of 1000 mg/m(2) on Day 1 and dexamethasone at a dose of 40 mg per day on Days 1-4 and 9-12, repeated on Day 22) as initial therapy followed by stein cell mobilization, harvest, and finally ASCT. RESULTS. No significant difference was observed in the proportion of patients undergoing ASCT (VAD [86%] vs Cy-Dex [87%]). During the first 4 months after the initiation of therapy, the mortality rates were 5.8% for VAD and 1.9% for Cy-Dex (P =.08). The response rates after ASCT were comparable (partial response or better: VAD: 80% vs Cy-Dex: 81%). In both groups, the median event-free survival was 29 months, and the overall survival rate at 3 years was 75%. CONCLUSIONS. The current results indicated that Cy-Dex before ASCT has efficacy comparable to that of VAD. It also demonstrated that a short course of alkylater therapy using cyclophosphamide does not affect stem cell harvest or transplantation.
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50.
  • Mortensen, Jens Jorgen, et al. (författare)
  • GPAW: An open Python package for electronic structure calculations
  • 2024
  • Ingår i: Journal of Chemical Physics. - 1089-7690 .- 0021-9606. ; 160:9
  • Tidskriftsartikel (refereegranskat)abstract
    • We review the GPAW open-source Python package for electronic structure calculations. GPAW is based on the projector-augmented wave method and can solve the self-consistent density functional theory (DFT) equations using three different wave-function representations, namely real-space grids, plane waves, and numerical atomic orbitals. The three representations are complementary and mutually independent and can be connected by transformations via the real-space grid. This multi-basis feature renders GPAW highly versatile and unique among similar codes. By virtue of its modular structure, the GPAW code constitutes an ideal platform for the implementation of new features and methodologies. Moreover, it is well integrated with the Atomic Simulation Environment (ASE), providing a flexible and dynamic user interface. In addition to ground-state DFT calculations, GPAW supports many-body GW band structures, optical excitations from the Bethe-Salpeter Equation, variational calculations of excited states in molecules and solids via direct optimization, and real-time propagation of the Kohn-Sham equations within time-dependent DFT. A range of more advanced methods to describe magnetic excitations and non-collinear magnetism in solids are also now available. In addition, GPAW can calculate non-linear optical tensors of solids, charged crystal point defects, and much more. Recently, support for graphics processing unit (GPU) acceleration has been achieved with minor modifications to the GPAW code thanks to the CuPy library. We end the review with an outlook, describing some future plans for GPAW.
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