| 1. |
- Fagerström Kristensen, Ingrid, et al.
(författare)
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Comparative Proton and Photon Treatment Planning in Pediatric Patients with Various Diagnoses
- 2015
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Ingår i: International Journal of Particle Therapy. - 2331-5180. ; 2:2, s. 367-375
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Radiation therapy with protons, owing to its physical properties, can beadvantageous for the treatment of children. This study was conducted in order to quantify the advantages of proton therapy from a treatment planning point of view in a consecutive, realistic, and mixed pediatric/adolescent population with varying diagnoses and target locations.Patients and Methods: Forty-five patients treated with conventional 3 dimensional conformal radiation therapy photon radiation therapy were retrospectively re-planned with scanned proton beams. Treatment sites represented were the central nervous system, head and neck, thorax, and abdomen. Median age was 8 years (range, 2-18 years). All plans were optimized with intensity-modulated proton therapy (multi-field optimization). We analyzed a number of dose-volume descriptors for planned targetvolumes (PTVs). Organ-specific mean doses and relevant DV -values were derived fororgans at risk. In addition, homogeneity index, conformity index, treated volume, and integral dose were calculated for each treatment plan. The Wilcoxon matched-pairs signed rank test was used for studying differences between these variables for the 2 treatment modalities.Results: Planned target volume coverage (V95%) was similar when comparing photons and protons. Conformity and homogeneity indices were similar or better for protons for most cases. In general, doses to organs at risk were lower with protons. In cases with organs at risk in close vicinity to the PTV, the gain with protons is less.Conclusions: The patient cohort benefits from reduced integral dose with protons compared with photons. Patients with tumors in the central nervous system, head and neck, upper mediastinum, and some abdominal locations will gain significantly if treated with protons compared with photons. For 7 of the 45 consecutive patients studied (whole brain, whole lung, whole abdomen, flank treatment), we found no gain with protons (difference in integral dose less than 8%).
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| 2. |
- Jespersen, Henrik, et al.
(författare)
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Concomitant use of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study): protocol for a multicenter phase II open label study.
- 2019
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Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- While recent years have seen a revolution in the treatment of metastatic cutaneous melanoma, no treatment has yet been able to demonstrate any prolonged survival in metastatic uveal melanoma. Thus, metastatic uveal melanoma remains a disease with an urgent unmet medical need. Reports of treatment with immune checkpoint inhibitors have thus far been disappointing. Based on animal experiments, it is reasonable to hypothesize that the effect of immunotherapy may be augmented by epigenetic therapy. Proposed mechanisms include enhanced expression of HLA class I and cancer antigens on cancer cells, as well as suppression of myeloid suppressor cells.The PEMDAC study is a multicenter, open label phase II study assessing the efficacy of concomitant use of the PD1 inhibitor pembrolizumab and the class I HDAC inhibitor entinostat in adult patients with metastatic uveal melanoma. Primary endpoint is objective response rate. Eligible patients have histologically confirmed metastatic uveal melanoma, ECOG performance status 0-1, measurable disease as per RECIST 1.1 and may have received any number of prior therapies, with the exception of anticancer immunotherapy. Twenty nine patients will be enrolled. Patients receive pembrolizumab 200mg intravenously every third week in combination with entinostat 5mg orally once weekly. Treatment will continue until progression of disease or intolerable toxicity or for a maximum of 24months.The PEMDAC study is the first trial to assess whether the addition of an HDAC inhibitor to anti-PD1 therapy can yield objective anti-tumoral responses in metastatic UM.ClinicalTrials.gov registration number: NCT02697630 . (Registered 3 March 2016). EudraCT registration number: 2016-002114-50.
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| 3. |
- Kristensen, Ingrid, et al.
(författare)
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A dose based approach for evaluation of inter-observer variations in target delineation
- 2017
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Ingår i: Technical Innovations and Patient Support in Radiation Oncology. - : Elsevier. - 2405-6324. ; 3-4, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Substantial inter-observer variations in target delineation have been presented previously. Target delineation for paediatric cases is difficult due to the small number of children, the variation in paediatric targets, the number of study protocols, and the individual patient's specific needs and demands. Uncertainties in target delineation might lead to under-dosage or over-dosage. The aim of this work is to apply the concept of a consensus volume and good quality treatment plans to visualise and quantify inter-observer target delineation variations in dosimetric terms in addition to conventional geometrically based volume concordance indices.Material and methods: Two paediatric cases were used to demonstrate the potential of adding dose metrics when evaluating target delineation diversity; Hodgkin's disease (case 1) and rhabdomyosarcoma of the parotid gland (case 2). The variability in target delineation (PTV delineations) between six centres was quantified using the generalised conformity index, CIgen, generated for volume overlap. The STAPLE algorithm, as implemented in CERR, was used for both cases to derive a consensus volumes. STAPLE is a probabilistic estimate of the true volume generated from all observers. Dose distributions created by each centre for the original target volumes were then applied to this consensus volume.Results: A considerable variation in target segmentation was seen in both cases. For case 1 the variation was 374-960 cm3 (average 669 cm3) and for case 2; 65-126 cm3 (average 109 cm3). CIgen were 0.53 and 0.70, respectively. The DVHs in absolute volume displayed for the delineated target volume as well as for the consensus volume adds information on both ''compliant" target volumes as well as outliers which are hidden with just the use of concordance indices.Conclusions: The DVHs in absolute volume add valuable and easily understood information to various indices for evaluating uniformity in target delineation.
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| 4. |
- Nilsson, Madeleine, et al.
(författare)
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Patientens delaktighet i val av vårdgivare : En litteratur review
- 2018
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Ingår i: Nordisk tidsskrift for helseforskning. - : UiT The Arctic University of Norway. - 1504-3614 .- 1891-2982. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The idea behind care choice is that healthcare providers would be more responsive to patients’ health problems and needs and in doing so compete with increased quality and that patients should be able to choose from this. The question is how patients choose a healthcare provider by themselves. The aim was to describe what affected when patients chose healthcare providers. A literature review was carried out. The results showed that patients’ choice of healthcare providers depended on the following three themes: their own care experiences, caring relationships with staff and service provided by caregivers. The underlying idea of care choice is competition based on quality of care, but the results show that patients make their choices based on other factors as described in the result and therefore improvement can be achieved if focus is placed on being responsive for patient care needs.
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| 5. |
- Tengvall, Katarina, 1980-, et al.
(författare)
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Molecular mimicry between Anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 116:34, s. 16955-16960
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is a chronic inflammatory, likely autoimmune disease of the central nervous system with a combination of genetic and environmental risk factors, among which Epstein-Barr virus (EBV) infection is a strong suspect. We have previously identified increased autoantibody levels toward the chloride-channel protein Anoctamin 2 (ANO2) in MS. Here, IgG antibody reactivity toward ANO2 and EBV nuclear antigen 1 (EBNA1) was measured using bead-based multiplex serology in plasma samples from 8,746 MS cases and 7,228 controls. We detected increased anti-ANO2 antibody levels in MS (P = 3.5 x 10(-36)) with 14.6% of cases and 7.8% of controls being ANO2 seropositive (odds ratio [OR] = 1.6; 95% confidence intervals [95% CI]: 1.5 to 1.8). The MS risk increase in ANO2-seropositive individuals was dramatic when also exposed to 3 known risk factors for MS: HLA-DRB1*15: 01 carriage, absence of HLA-A*02: 01, and high anti-EBNA1 antibody levels (OR = 24.9; 95% CI: 17.9 to 34.8). Reciprocal blocking experiments with ANO2 and EBNA1 peptides demonstrated antibody cross-reactivity, mapping to ANO2 [aa 140 to 149] and EBNA1 [aa 431 to 440]. HLA gene region was associated with anti-ANO2 antibody levels and HLADRB1*04: 01 haplotype was negatively associated with ANO2 seropositivity (OR = 0.6; 95% CI: 0.5 to 0.7). Anti-ANO2 antibody levels were not increased in patients from 3 other inflammatory disease cohorts. The HLA influence and the fact that specific IgG production usually needs T cell help provides indirect evidence for a T cell ANO2 autoreactivity in MS. We propose a hypothesis where immune reactivity toward EBNA1 through molecular mimicry with ANO2 contributes to the etiopathogenesis of MS.
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| 6. |
- Wigren, Maria, et al.
(författare)
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Lack of Ability to Present Antigens on Major Histocompatibility Complex Class II Molecules Aggravates Atherosclerosis in ApoE-/- Mice
- 2019
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Ingår i: Circulation. - 1524-4539. ; 139:22, s. 2554-2566
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hypercholesterolemic mice lacking factors required for activation of CD4+ T cells are characterized by reduced development of atherosclerosis. Consequently, it has been assumed that atherosclerosis involves loss of tolerance against modified self-antigens generated in response to hypercholesterolemia and that presentation of such antigens on major histocompatibility complex class II (MHCII) leads to activation of proatherogenic Th1 cells. In this study, we wanted to determine the role of antigen presentation on MHCII in atherosclerosis development.METHODS: Apolipoprotein E (ApoE-/-) mice deficient for MHCII (ApoE-/-MHCII-/-) were used to study the role of MHCII in atherosclerosis development.RESULTS: Compared with ApoE-/- mice, ApoE-/-MHCII-/- mice had reduced levels of CD4+ T cells, immunoglobulin G and M levels, and Th1 and Th2 cytokines in plasma. CD8+ T cells were increased and regulatory T cells were reduced both in spleen and in lesions of ApoE-/-MHCII-/- mice. Decreased plasma levels of inflammatory cytokines in ApoE-/-MHCII-/- mice indicated reduced systemic inflammation. Despite this, ApoE-/-MHCII-/- mice had significantly more atherosclerosis as assessed by en face Oil Red O staining of the aorta (4.7±2.9% versus 1.9±1.3%; P<0.01) and cross-sectional area of subvalvular lesions (7.7±2.2×105 µm2 versus 4.6±2.8×105 µm2; P<0.05). Cell transfer and blocking antibody studies suggested that loss of regulatory T cells is the most important cause of aggravated atherosclerosis in ApoE-/-MHCII-/- mice.CONCLUSIONS: Our observations demonstrate that antigen presentation on MHCII has important protective functions in atherosclerosis and that this is primarily the result of activation of regulatory T cells. These findings have implications for understanding the possible risks and benefits of immunosuppressive therapy in patients with cardiovascular disease.
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| 7. |
- Aguiar Borges, Luciane, et al.
(författare)
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White Paper on Nordic Sustainable Cities
- 2017
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Rapport (populärvet., debatt m.m.)abstract
- Rapid urbanisation is one of today’s biggest global challenges. Nordic Sustainable Cities is a flagship project under the Nordic Prime Ministers’ initiative Nordic Solutions to Global Challenges that seeks to shed light on this challenge from a Nordic perspective.The White Paper on Nordic Sustainable Cities develops a narrative to describe the “Nordic Sustainable City”. It forms a basis for the knowledge sharing effort that will be carried out by Nordic Innovation, Nordregio’s sister institution under the Nordic Council of Ministers in 2018. This work aims to export Nordic stories as a means of branding the Nordic Region and contributing to global efforts towards urban sustainability.
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| 8. |
- Ahnesjö, Ingrid, et al.
(författare)
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En beteende-ekologisk forskningsperiod på Klubbans biologiska station : Rapport från återträff med Doktorer som disputerade (1983-2001) på avhandlingar med fältarbete på Klubbans Biologiska station. I en värld av kantnålar, stubbar, spiggar och nudingar.
- 2018
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Rapport (populärvet., debatt m.m.)abstract
- We had the fortune as PhD-students and scientists in Animal Ecology at Uppsala University, to spend joyful and creative field work summers at Klubban Biological Station, during the 1980-90’s. A reunion in June 2018 resulted in this report highlighting research on pipefishes, gobies, sticklebacks and nudibranchs. Our research on these animals have provided novel insights and knowledge of the process of sexual selection and paternal care. These animals have, in many aspects, now become model organisms in evolutionary behavioral ecology in marine environments. Our list of publications provides many examples of how environmental factors influence how sexual selection and mate choice operate, how predictors like potential reproductive rates, operational sex ratios work and how male parental care is prominent in influencing selection. This research, that started at Klubban, has broadened our understanding of the ecological importance of shallow marine areas. The evolutionary understanding of how males and females can behave and how adaptive traits are selected in interaction with social and an increasingly changing ambient environment is in focus in our continued scientific endeavors. We have happily compiled this report illustrating how science and scientist can stimulate each other at a wonderful place like Klubban Biological Station, with the access to amazing organisms like pipefishes, gobies, sticklebacks and nudibranchs.
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| 9. |
- Allbrand, Marianne, 1958-, et al.
(författare)
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Placental gene expression of inflammatory markers and growth factors : a case control study of obese and normal weight women
- 2015
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Ingår i: Journal of Perinatal Medicine. - : Walter de Gruyter. - 0300-5577 .- 1619-3997. ; 43:2, s. 159-164
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To survey the placental gene expression of inflammatory markers and growth factors in non-smoking obese women with an uncomplicated pregnancy without associated morbidity and delivery at term compared with normal weight women.Methods: Placental tissue samples from 32 obese women (body mass index, BMI >= 35.0 kg/m(2)) were compared with samples from 94 normal weight women (BMI 18.5-25.0 kg/m(2)) matched for age (+/- 1 year), gestational age (+/- 3 days), parity and mode of delivery. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to analyse toll receptor-2 and -4, interleukin-6 and -8, tumour necrosis factor-alpha, leptin, adiponectin, insulin-like growth factor-1 and -2, hepatocyte growth factor, hepatocyte growth factor receptor and insulin receptor.Results: There was no significant difference in gene expression in placental tissue samples from obese and normal weight women.Conclusion: We found no difference in the occurrence of inflammatory marker and growth factor mRNA levels in placental tissue samples from a large group of obese women without associated morbidity and with healthy infants compared to a closely matched control group of healthy normal weight women. Compared with the previous studies, this anomalous finding may be explained by the absence of associated morbidity in the obese women in our study.
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| 10. |
- Alping, Peter, et al.
(författare)
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Validation of the Swedish Multiple Sclerosis Register Further Improving a Resource for Pharmacoepidemiologic Evaluations
- 2019
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Ingår i: Epidemiology. - : Lippincott Williams & Wilkins. - 1044-3983 .- 1531-5487. ; 30:2, s. 230-233
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish Multiple Sclerosis Register is a national register monitoring treatment and clinical course for all Swedish multiple sclerosis (MS) patients, with high coverage and close integration with the clinic. Despite its great value for epidemiologic research, it has not previously been validated. In this brief report, we summarize a large validation of >3,000 patients in the register using clinical chart review in the context of the COMBAT-MS study. While further improving the data quality for a central cohort of patients available for future epidemiologic research, this study also allowed us to estimate the accuracy and completeness of the register data.
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