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1.
  • Klionsky, Daniel J., et al. (author)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Research review (peer-reviewed)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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  • Holmström, Margareta, et al. (author)
  • SWEDISH NATIONAL REGISTRY FOR BLEEDING DISORDERS – A SECOND REPORT
  • 2019
  • In: EAHAD 2019.
  • Conference paper (peer-reviewed)abstract
    • Introduction: Hemophilia Care in Sweden is centralized to three different and certified European Hemophilia Care Centers (EHCCs) (Stockholm, Gothenburg and Malmö[f1]). A recent web- based National registry has been set up for patients with bleeding disorders in Sweden. The registry is mainly funded by Swedish authorities. Methods: A multi- professional steering committee is running the registry with representatives from all three centers including physicians, nurses, physiotherapist and also a patient representative. A web- based platform, Real- Q, is used for the registry. Results: By the 31st Dec 2017, a total number of 1030 patients with bleeding disorders were included in the registry, mainly patients with hemophilia A, B and Von Willebrand disease. Data regarding bleedings, treatment modality and type of product, inhibitor status, viral infections are collected. Likewise patient reported outcome measurements (PROM)- such as pain and quality of life[.The number of patients with hemophilia A, B and Von Willebrand disease in 2016 resp 2017 were as follows:Hemophilia A; n = 243 in 2016 and n= 691 in 2017.Hemophilia B: n = 49 in 2016 and n = 191 in 2017.Von Willebrand disease: n = 11 in 2016 and n = 152 in 2017.[LMW1] are registered.[LMW2] are registered on a regular basis? Discussion/Conclusion: The number of patients in the Swedish National Registry for bleeding disorders has increased significantly during the last year; from a total of 308 Dec 31st 2016 to 1030 in Dec 31st 2017. Increasing amount of data will enable further evaluation of treatment data and also joint status, quality of life and bleeding reports.
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  • Holmström, Margareta, et al. (author)
  • Swedish national registry for bleeding disorders - first report
  • 2018
  • In: 11th Annual Congress of the European Association for Haemophilia and Allied Disorders 2018, 7–9 February 2018, Madrid, Spain. Haemophilia, 24 (S1). - : Wiley. - 1365-2516.
  • Conference paper (other academic/artistic)abstract
    • Introduction : Hemophilia care in Sweden is centralized to 3 centers localized in Gothenburg, Malmö and Stockholm. All centers are certi-fied as European Hemophilia Comprehensive Care Centers (EHCCs). Recently a web- based Swedish national registry has been established with funding from Swedish authorities. Methods : One of the conclusions from the earlier reports from the Swedish agency for health technology assessment and assessment of social services (SBU) and the Dental and Pharmaceutical benefits agency (TLV) was that a national registry for hemophilia and other bleeding disorders was needed to be able to follow the long- term effects of the disease and treatment strategies. An application was submitted in 2012 to apply for funding from Swedenʹs municipali-ties and count councils (SKL). The registry was validated as an official national registry. A multi- professional steering committee is running the registry with representatives from all 3 hemophilia centers includ-ing physicians, nurses, physiotherapist and a patient representative. Support regarding legal aspects, IT- solutions, statistics and economy is provided by QRC Stockholm. Results : By now, 780 patients with bleeding disorders are included in the Swedish national Registry and data regarding bleedings, treat-ment with factor concentrate, inhibitor status, mutations, viral infections such as hepatitis C and HIV are collected. Patient reported outcome measurements (PROM)- such as pain and quality of life - HJHS and target joints are followed continuously. Discussion/Conclusion : The establishment of a Swedish National Registry enables us to perform national annual reports, have a close follow- up of our patients and perform clinical research. Currently are working on an on- line patient treatment application recording directly into the registry. Data from the registry will be an important tool for further evaluation of the treatment of hemophilia and how it affects the long- term consequences of the disease.
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  • Jönsson, Göran B, et al. (author)
  • The retinoblastoma gene undergoes rearrangements in BRCA1-deficient basal-like breast cancer.
  • 2012
  • In: Cancer Research. - 1538-7445. ; 72:16, s. 4028-4036
  • Journal article (peer-reviewed)abstract
    • Breast tumors from BRCA1 germ line mutation carriers typically exhibit features of the basal-like molecular subtype. However, the specific genes recurrently mutated as a consequence of BRCA1 dysfunction have not been fully elucidated. In this study, we utilized gene expression profiling to molecularly subtype 577 breast tumors, including 72 breast tumors from BRCA1/2 mutation carriers. Focusing on the RB1 locus, we analyzed 33 BRCA1-mutated, 36 BRCA2-mutated and 48 non-BRCA1/2-mutated breast tumors using a custom-designed high-density oligomicroarray covering the RB1 gene. We found a strong association between the basal-like subtype and BRCA1-mutated breast tumors and the luminal B subtype and BRCA2-mutated breast tumors. RB1 was identified as a major target for genomic disruption in tumors arising in BRCA1 mutation carriers and in sporadic tumors with BRCA1 promoter-methylation, but rarely in other breast cancers. Homozygous deletions, intragenic breaks, or microdeletions were found in 33% of BRCA1-mutant tumors, 36% of BRCA1 promoter-methylated basal-like tumors, 13% of non-BRCA1 deficient basal-like tumors, and 3% of BRCA2-mutated tumors. In conclusion, RB1 was frequently inactivated by gross gene disruption in BRCA1-related hereditary breast cancer and BRCA1-methylated sporadic basal-like breast cancer, but rarely in BRCA2-hereditary breast cancer and non-BRCA1-deficient sporadic breast cancers. Together, our findings demonstrate the existence of genetic heterogeneity within the basal-like breast cancer subtype that is based upon BRCA1-status.
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  • Machiela, Mitchell J., et al. (author)
  • Characterization of Large Structural Genetic Mosaicism in Human Autosomes
  • 2015
  • In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
  • Journal article (peer-reviewed)abstract
    • Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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  • Machiela, Mitchell J, et al. (author)
  • Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
  • 2016
  • In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
  • Journal article (peer-reviewed)abstract
    • To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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  • Paulsson, Kajsa, et al. (author)
  • The genomic landscape of high hyperdiploid childhood acute lymphoblastic leukemia
  • 2015
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47:6, s. 672-676
  • Journal article (peer-reviewed)abstract
    • High hyperdiploid (51-67 chromosomes) acute lymphoblastic leukemia (ALL) is one of the most common childhood malignancies, comprising 30% of all pediatric B cell-precursor ALL. Its characteristic genetic feature is the nonrandom gain of chromosomes X, 4, 6, 10, 14, 17, 18 and 21, with individual trisomies or tetrasomies being seen in over 75% of cases, but the pathogenesis remains poorly understood. We performed whole-genome sequencing (WGS) (n = 16) and/or whole-exome sequencing (WES) (n = 39) of diagnostic and remission samples from 51 cases of high hyperdiploid ALL to further define the genomic landscape of this malignancy. The majority of cases showed involvement of the RTK-RAS pathway and of histone modifiers. No recurrent fusion gene-forming rearrangement was found, and an analysis of mutations on trisomic chromosomes indicated that the chromosomal gains were early events, strengthening the notion that the high hyperdiploid pattern is the main driver event in this common pediatric malignancy.
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  • Yang, Yaohua, et al. (author)
  • Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk
  • 2019
  • In: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 79:3, s. 505-517
  • Journal article (peer-reviewed)abstract
    • DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 x 10(-7). Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. Significance: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
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  • Aaltonen, Kristina, et al. (author)
  • Association between insulin-like growth factor-1 receptor (IGF1R) negativity and poor prognosis in a cohort of women with primary breast cancer
  • 2014
  • In: BMC Cancer. - : BioMed Central. - 1471-2407. ; 14:794
  • Journal article (peer-reviewed)abstract
    • Background: Resistance towards endocrine therapy is a great concern in breast cancer treatment and may partly be explained by the activation of compensatory signaling pathways. The aim of the present study was to investigate if the insulin-like growth factor-1 receptor (IGF1R) signaling pathway was activated or deregulated in breast cancer patients and to explore if any of the markers were prognostic, with or without adjuvant tamoxifen. This signaling pathway has been suggested to cause estrogen independent cell growth and thus contribute to resistance to endocrine treatment in estrogen receptor (ER) positive breast cancer. Methods: The protein expression of IGF1R, phosphorylated Mammalian Target of Rapamycin (p-mTOR) and phosphorylated S6 ribosomal protein (p-S6rp) were investigated by immunohistochemistry using tissue microarrays in two patient cohorts. Cohort I (N = 264) consisted of mainly postmenopausal women with stage II breast cancer treated with tamoxifen for 2 years irrespective of ER status. Cohort II (N = 206) consisted of mainly medically untreated, premenopausal patients with node-negative breast cancer. Distant disease-free survival (DDFS) at 5 years was used as end-point for survival analyses. Results: We found that lower IGF1R expression was associated with worse prognosis for tamoxifen treated, postmenopausal women (HR = 0.70, 95% CI = 0.52 - 0.94, p = 0.016). The effect was seen mainly in ER-negative patients where the prognostic effect was retained after adjustment for other prognostic markers (adjusted HR = 0.49, 95% CI = 0.29 - 0.82, p = 0.007). Expression of IGF1R was associated with ER positivity (p less than 0.001) in the same patient cohort. Conclusions: Our results support previous studies indicating that IGF1R positivity reflects a well differentiated tumor with low metastatic capacity. An association between lack of IGF1R expression and worse prognosis was mainly seen in the ER-negative part of Cohort I. The lack of co-activation of downstream markers (p-mTOR and p-S6rp) in the IGF1R pathway suggested that the prognostic effect was not due to complete activation of this pathway. Thus, no evidence could be found for a compensatory function of IGF1R signaling in the investigated cohorts.
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  • Adwall, Linda, et al. (author)
  • Antibiotikaprofylax vid bröstkirurgi? Ja, men inte till alla. Kvalitetsdata fran Uppsala läns landsting ger förslag till riktlinjer
  • 2013
  • In: Läkartidningen. - Stockholm : Läkartidningen förlag. - 0023-7205 .- 1652-7518. ; 110:5, s. 213-215
  • Journal article (other academic/artistic)abstract
    • I randomiserade studier har det visats att antibiotikaprofylax minskar infektionsfrekvensen med cirka 30–40 procent vid bröstcancerkirurgi.Statens beredning för medicinsk utvärdering rekommenderar därför sedan 2010 antibiotikaprofylax vid bröstcancerkirurgi.I Uppsala läns landsting fick totalt cirka 10 procent postoperativ infektion efter bröstkirurgi under 2009 och 2010. Ingreppets omfattning relaterar klart till risken för infektion.Vi diskuterar i denna artikel när det kan vara indicerat att ge eller inte ge antibiotikaprofylax vid bröstcancerkirurgi.
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  • Ahrens, Wolfgang, et al. (author)
  • Risk factors for extrahepatic biliary tract carcinoma in men: medical conditions and lifestyle: results from a European multicentre case-control study
  • 2007
  • In: European Journal of Gastroenterology and Hepathology. - 1473-5687. ; 19:8, s. 623-630
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: To identify risk factors of carcinoma of the extrahepatic biliary tract in men. METHODS: Newly diagnosed and histologically confirmed patients, 35-70 years old, were interviewed between 1995 and 1997 in Denmark, Sweden, France, Germany and Italy. Population controls were frequency-matched by age and region. Adjusted odds ratios and 95%-confidence intervals were estimated by logistic regression. RESULTS: The analysis included 153 patients and 1421 controls. The participation proportion was 71% for patients and 61% for controls. Gallstone disease was corroborated as a risk factor for extrahepatic biliary tract carcinoma in men (odds ratio 2.49; 95% confidence interval 1.32-4.70), particularly for gall bladder tumors (odds ratio 4.68; 95% confidence interval 1.85-11.84). For a body mass index [height (m) divided by squared weight (kg2)] >30 at age 35 years, an excess risk was observed (odds ratio 2.58; 95% confidence interval 1.07-6.23, reference: body mass index 18.5-25) that was even stronger if the body mass index was >30 for the lowest weight in adulthood (odds ratio 4.68; 95% confidence interval 1.13-19.40). Infection of the gall bladder, chronic inflammatory bowel disease, hepatitis or smoking showed no clear association, whereas some increase in risk was suggested for consumption of 40-80 g alcohol per day and more. CONCLUSIONS: Our study corroborates gallstones as a risk indicator in extrahepatic biliary tract carcinoma. Permanent overweight and obesity in adult life was identified as a strong risk factor for extrahepatic biliary tract carcinoma, whereas we did not find any strong lifestyle-associated risk factors. Inconsistent results across studies concerning the association of extrahepatic biliary tract carcinoma with overweight and obesity may be explained by the different approaches to assess this variable.
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  • Aliasgharzad, Nasser, et al. (author)
  • Acidification of a sandy grassland favours bacteria and disfavours fungal saprotrophs as estimated by fatty acid profiling
  • 2010
  • In: Soil Biology & Biochemistry. - : Elsevier BV. - 0038-0717. ; 42:7, s. 1058-1064
  • Journal article (peer-reviewed)abstract
    • We have investigated the structure of a microbial community in semi-natural sandy grassland in southeast Sweden. The sand is rich in lime, but in most places the soil is decalcified in the upper layers, and therefore this site shows a large variation in pH within short distances. We collected samples at three different soil depths (0-10 cm, 10-20 cm and 20-30 cm) and found the pH to range from 5 to 8 in the topsoil and from 4.5 to 9.5 in the deepest layer. The abundance of saprophytic fungi and bacteria was investigated using signature phospholipid fatty acids and arbuscular mycorrhizal fungi (AMF) using the neutral lipid fatty acid 16:1 omega 5. The PLFA pattern of the topsoil was different from that in the other two layers, as indicated by principal component analysis. The saprotrophic fungi were associated with high pH, and bacteria with low pH in these sandy soils. No relation was found between pH and AMF in the topsoil, while a positive relation was found in the deepest soil layer. The saprophytic fungi-to-bacteria ratio was constant with depth, while the AMF-to-bacteria ratio increased with soil depth. The results showed that high soil pH favoured fungal saprophytes in sandy grasslands and that AMF are relatively more abundant than the other two groups in deeper soil layers: particularly so when the pH is high. (C) 2010 Elsevier Ltd. All rights reserved.
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  • Alkan Olsson, Johanna, et al. (author)
  • Mapping the governance complex of land use policies for compensation
  • 2019
  • Conference paper (other academic/artistic)abstract
    • Ecological compensation is the latest member of a growing family of concepts aimed at reducing degradation of environmental quality. This and other concepts of the family – like ecosystem services, green infrastructure, and nature-based solutions – have been subject to a range of different interpretations and subsequent implementation practices. The result is a complex governance system with unclear boundaries and implications for the management efforts of environmental quality. In this paper, we seek to map and disentangle this complexity – with a particular focus on ecological compensation and related concepts (such as biodiversity offsetting and no net loss), which all have gained momentum in recent years and which share the notion that intrusion in nature should be compensated in one way or the other. In a first step, we seek to map similarities, differences and overlaps, between the concepts, by using a set of analytical categories including: the origin of the concept (scientific or policy context), the aim of its application, the type of decision-making process it generates, its relation to urban or rural contexts, and the extent to which it has been subjected to regulation. In a second step, and as a result of this mapping, we will advance knowledge about how governments, municipalities and business actors in different ways work with environmental quality, ecosystem services and biodiversity. First, we draw conclusions about the degree to which the concepts under scrutiny are mutually reinforcing or competing. Second, our analysis enables conclusions about why some concepts are preferred in certain institutional contexts and what institutional preconditions are needed for their use. Third, we discuss possible implications of this governance complexity for questions of effectiveness and legitimacy.
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  • Andersson-Engels, Stefan, et al. (author)
  • In vivo luminescence imaging and tomography using upconverting nanoparticles as contrast agents
  • 2012
  • In: 2012 Asia Communications and Photonics Conference. - 2162-108X. ; , s. 2-3
  • Conference paper (peer-reviewed)abstract
    • Upconverting nanoparticles have recently drawn increasingly attention as contrast agents for optical bioimaging. They enable autofluorescence-free imaging within the tissue optical window, and improved spatial resolution as compared to conventional fluorescence-based contrast agents. (C) 2012 Optical Society of America
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  • Andersson, Ulf, 1963-, et al. (author)
  • Pathways to arithmetic fact retrieval and percentage calculation in adolescents
  • 2017
  • In: British Journal of Educational Psychology. - : John Wiley & Sons. - 0007-0998 .- 2044-8279. ; 87:4, s. 647-663
  • Journal article (peer-reviewed)abstract
    • BackgroundDeveloping sufficient mathematical skills is a prerequisite to function adequately in society today. Given this, an important task is to increase our understanding regarding the cognitive mechanisms underlying young people's acquisition of early number skills and formal mathematical knowledge.AimsThe purpose was to examine whether the pathways to mathematics model provides a valid account of the cognitive mechanisms underlying symbolic-number processing and mathematics in adolescents. The pathways model states that the three pathways should provide independent support to symbolic-number skill. Each pathway's unique contribution to formal mathematics varies depending on the complexity and demand of the tasks.SampleThe study used a sample of 114 adolescents (71 girls). Their mean age was 14.60 years (SD = 1.00).MethodsThe adolescents were assessed on tests tapping the three pathways and general cognitive abilities (e.g., working memory). A structural equation path analysis was computed.ResultsSymbolic-number comparison was predicted by the linguistic pathway, the quantitative pathway, and processing speed. The linguistic pathway, quantitative pathways, and symbolic-number comparison predicted arithmetic fact retrieval. The linguistic pathway, working memory, visual analogies, and symbolic-number comparison predicted percentage calculation.ConclusionsThere are both similarities and differences in the cognitive mechanisms underlying arithmetic fact retrieval and percentage calculation in adolescents. Adolescents’ symbolic-number processing, arithmetic fact retrieval, and percentage calculation continue to rely on the linguistic pathways, whereas the reliance upon the spatial pathway has ceased. The reliance upon the quantitative pathway varies depending on the task.
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  • Anrup, Roland, et al. (author)
  • Centrala universitetsvärden hotas av bolagiseringsidén
  • 2013
  • In: Dagens nyheter. - 1101-2447.
  • Journal article (pop. science, debate, etc.)abstract
    • Högskolestiftelser. Förslaget att driva svenska universitet i stiftelseform ­öppnar för bolagisering. Men det är ingen riktig utredning, utan en politisk pamflett utan ­eftertanke. Privatisering av universitet hotar både oberoendet, forskningskvaliteten och samhällsnyttan, skriver 36 forskare vid svenska högskolor och universitet.
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  • Aurell, Emelie, et al. (author)
  • Mikroplaster : Redovisning av regeringsuppdrag om källor till mikroplaster och förslag på åtgärder för minskade utsläpp i Sverige
  • 2017
  • Reports (other academic/artistic)abstract
    • I augusti 2015 fick Naturvårdsverket i uppdrag från regeringen att identifiera viktigare källor i Sverige till utsläpp av mikroplaster till havet och verka för att reducera utsläppen från dessa källor. I den här rapporten redovisar Naturvårdsverket uppdraget. Vi presenterar resultaten från den första, övergripande kartläggningen av källor till och spridning av mikroplaster i Sverige, en bedömning av vilka av de kartlagda källorna som primärt bör åtgärdas samt vilka steg som behöver tas för att förebygga utsläpp och minska spridning av mikroplaster till hav, sjöar och vattendrag från dessa källor.Förekomsten av mikroplast i den marina miljön har uppmärksammats allt mer under senare år, inte minst på global nivå. Mikroplast är ett samlingsnamn för små, små plastfragment (1 nm till 5 mm). De mikroplaster som hittats i världshaven, men även i sötvattensystem, har olika ursprung. Mikroplast kan bildas oavsiktligt när plastföremål slits och plastpartiklar frigörs, eller när vi inte återanvänder, återvinner eller slänger plastmaterial på rätt sätt utan plasten blir skräp som succesivt bryts ned till mindre och mindre bitar i naturen. Det finns också plast som från början tillverkas som små pellets eller korn.Utgångspunkten för arbetet har varit miljökvalitetsmålen Hav i balans samt levande kust och Levande sjöar och vattendrag samt målet om Giftfri miljö. Reduceradeutsläpp av mikroplaster till hav, sjöar och vattendrag bidrar till att nå dessa mål.Uppdraget har genomförts av Naturvårdsverket i samarbete med Havs- och vattenmyndigheten, andra berörda myndigheter, samt med deltagande av berörda organisationer och andra intressenter mellan augusti 2015 och maj 2017. Slutsatserna är Naturvårdsverkets egna.
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26.
  • Ayoola-Gustafsson, Kristin, et al. (author)
  • Enrichment of pathogenic ASXL1 variants among patients with primary refractory chronic myeloid leukemia
  • Other publication (other academic/artistic)abstract
    • In chronic myeloid leukemia in chronic phase (CP-CML), tyrosine kinase inhibitor (TKI) therapy is standard, yielding excellent long-term results. However, 5-10% of patients fail multiple TKIs, often resorting to allogeneic stem cell transplantation (Allo-SCT) with considerable risks. BCR::ABL1 kinase domain (KD) mutations and additional cytogenetic aberrations (ACA) represent common resistance mechanisms, but often the cause of resistance remains unknown. This study sequenced 54 myeloid neoplasm-related genes in 20 CP-CML patients refractory to TKI and without KD mutations or ACA, revealing pathogenic variants in 50% (n=10). ASXL1 mutations were most common (30%), followed by DNMT3A, IKZF1, GATA2, TP53 and NRAS. No pathogenic variant could be detected in a control cohort of 10 patients who were considered as optimal responders.
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  • Beral, V., et al. (author)
  • Ovarian Cancer and Body Size : Individual Participant Meta-Analysis Including 25,157 Women with Ovarian Cancer from 47 Epidemiological Studies
  • 2012
  • In: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 9:4
  • Journal article (peer-reviewed)abstract
    • Background: Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships. Methods and Findings: Individual data on 25,157 women with ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological studies were collected, checked, and analysed centrally. Adjusted relative risks of ovarian cancer were calculated, by height and by body mass index. Ovarian cancer risk increased significantly with height and with body mass index, except in studies using hospital controls. For other study designs, the relative risk of ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval [CI], 1.05-1.09; p<0.001); this relationship did not vary significantly by women's age, year of birth, education, age at menarche, parity, menopausal status, smoking, alcohol consumption, having had a hysterectomy, having first degree relatives with ovarian or breast cancer, use of oral contraceptives, or use of menopausal hormone therapy. For body mass index, there was significant heterogeneity (p<0.001) in the findings between ever-users and never-users of menopausal hormone therapy, but not by the 11 other factors listed above. The relative risk for ovarian cancer per 5 kg/m(2) increase in body mass index was 1.10 (95% CI, 1.07-1.13; p<0.001) in never-users and 0.95 (95% CI, 0.92-0.99; p = 0.02) in ever-users of hormone therapy. Conclusions: Ovarian cancer is associated with height and, among never-users of hormone therapy, with body mass index. In high-income countries, both height and body mass index have been increasing in birth cohorts now developing the disease. If all other relevant factors had remained constant, then these increases in height and weight would be associated with a 3% increase in ovarian cancer incidence per decade.
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28.
  • Beral, V., et al. (author)
  • Ovarian cancer and smoking: individual participant meta-analysis including 28 114 women with ovarian cancer from 51 epidemiological studies
  • 2012
  • In: The Lancet Oncology. - 1474-5488. ; 13:9, s. 946-956
  • Journal article (peer-reviewed)abstract
    • Background Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence. Methods Eligible epidemiological studies were identified by electronic searches, review articles, and discussions with colleagues. Individual participant data for 28 114 women with and 94 942 without ovarian cancer from 51 epidemiological studies were analysed centrally, yielding adjusted relative risks (RRs) of ovarian cancer in smokers compared with never smokers. Findings After exclusion of studies with hospital controls, in which smoking could have affected recruitment, overall ovarian cancer incidence was only slightly increased in current smokers compared with women who had never smoked (RR 1.06, 95% CI 1.01-1.11, p=0.01). Of 17 641 epithelial cancers with specified histology, 2314 (13%) were mucinous, 2360 (13%) endometrioid, 969 (5%) clear-cell, and 9086 (52%) serous. Smoking-related risks varied substantially across these subtypes (p(heterogeneity)<0.0001). For mucinous cancers, incidence was increased in current versus never smokers (1.79, 95% CI 1.60-2.00, p<0.0001), but the increase was mainly in borderline malignant rather than in fully malignant tumours (2.25, 95% CI 1.91-2.65 vs 1.49, 1.28-1.73; p(heterogeneity)=0.01; almost half the mucinous tumours were only borderline malignant). Both endometrioid (0.81, 95% CI 0.72-0.92, p=0.001) and clear-cell ovarian cancer risks (0.80, 95% CI 0.65-0.97, p=0.03) were reduced in current smokers, and there was no significant association for serous ovarian cancers (0.99, 95% CI 0.93-1.06, p=0.8). These associations did not vary significantly by 13 sociodemographic and personal characteristics of women including their body-mass index, parity, and use of alcohol, oral contraceptives, and menopausal hormone therapy. Interpretation The excess of mucinous ovarian cancers in smokers, which is mainly of tumours of borderline malignancy, is roughly counterbalanced by the deficit of endometrioid and clear-cell ovarian cancers. The substantial variation in smoking-related risks by tumour subtype is important for understanding ovarian carcinogenesis.
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29.
  • Berggren, Linda, et al. (author)
  • Between good intentions and practical constraints : Swedish teachers' perceptions of school lunch
  • 2021
  • In: Cambridge Journal of Education. - : Routledge. - 0305-764X .- 1469-3577. ; 51:2, s. 247-261
  • Journal article (peer-reviewed)abstract
    • In Sweden, pupils eat tax-funded school lunches, often in the company of teachers. This article focuses on Swedish compulsory school grade (ages 7-15) teachers' (n = 823) perceptions of the school lunch in terms of intentions and daily practice. Analysis was based on written answers for an open-ended question that was part of a questionnaire focusing on teachers' attitudes towards school lunch as a pedagogical activity. It was found that participating teachers saw the potential of the school lunch, placing emphasis on the social interaction that takes place in the school restaurant and the possibility of meeting pupils in a more informal setting. However, a key outcome was teachers' depictions of the struggle between ideals and reality with the effect that teachers were not always provided with favourable conditions for school lunch interactions. It is important to address this in order to improve meal-time practices and the experience of school lunch.
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30.
  • Berggren, Linda, 1983-, et al. (author)
  • Förutsättningar för en trivsam skollunch
  • 2023
  • In: Læring gennem mad og måltider i grundskolen. - : Cappelen Damm AS. - 9788202797744 - 9788202755423 ; , s. 131-146
  • Book chapter (peer-reviewed)abstract
    • This chapter highlights conditions for a pleasant school lunch based on experiences and perceptions from pupils, teachers, and head teachers. The empirical part of the study is based on a qualitative design using empathy-based stories, individual interviews, and a qualitative analysis of open comments from a questionnaire. Henri Lefebvre's theory of social production of space constitutes the theoretical framework, placing emphasis on how school lunch is experienced, perceived and conceived. The results show that these pupils, teachers and head teachers share the perception of school lunch as a space for socializing. Additionally, they show that conditions for a pleasant school lunch experience, chief among them the environment and time available, are not always favorable. The results presented in this chapter indicate that physical and organizational dimensions of school lunch need to be given more attention.
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31.
  • Berggren, Linda, 1983-, et al. (author)
  • Head teacher perspectives on school lunch : at variance with national policy
  • 2024
  • In: Health Education Journal. - : Sage Publications. - 0017-8969 .- 1748-8176. ; 83:1, s. 29-39
  • Journal article (peer-reviewed)abstract
    • Objective: Previous research indicates that head teachers in Sweden frequently fail to see school lunch as part of the educational activities of a school. This study contributes to an understanding of how head teachers in Sweden perceive and experience current national policy intentions related to school lunch.Design: Qualitative inquiry.Setting: Ten municipal state schools in Sweden.Method: Individual semi-structured interviews were conducted with 10 head teachers responsible for the compulsory education of 6- to 15-year-olds in state schools. Data from digitally recorded and transcribed interviews were thematically analysed.Results: Head teachers primarily saw school lunch as a means to ensure pupils were fed and energised. Their focus tended to be on what followed after school lunch in the form of academic performance and mood, rather than the stated intentions of national school meal policy. Head teachers stressed the value of a free and nutritious school lunch for social equality, and the importance of good collaboration with food service managers and school meal personnel, despite the difficulty of achieving this.Conclusion: This paper highlights a gap between head teachers' perspectives with respect to school lunch and official intentions stated in Swedish national school meals policy. The meanings head teachers saw as connected to school lunch were those of social equality and ensuring pupils were fed, rather than the wider potential envisioned by the authorities. This paper identifies factors that affect the possibility of realising national policy intentions for school lunch in Sweden.
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32.
  • Berggren, Linda, 1983- (author)
  • “It’s not really about the food, it’s about everything else” : pupil, teacher and head teacher experiences of school lunch in Sweden
  • 2021
  • Doctoral thesis (other academic/artistic)abstract
    • The school lunch is often associated with food, nutrition and health while the social, physical, pedagogical and cultural dimensions of the school lunch situation have not been given as much attention. Sweden is one of few countries in the world where tax-funded school meals are served to all pupils in compulsory school. This thesis highlights the school lunch situation from the perspectives of pupils, teachers and head teachers in Sweden. The overall aim is to contribute a deeper understanding of how these school actors perceive and experience the school lunch situation.The thesis is compiled from four papers. Paper 1 examine Nordic pupil’s perspectives on the healthiness of the meals in the context of school lunches. The remaining papers have been carried out in a Swedish context. Paper 2 examines pupil’s lived experiences of school lunch and how they relate to the social and physical dimensions of school lunch. Paper 3 examines teachers’ perceptions of the school lunch in terms of intentions and daily practice. Paper 4 examines head teachers’ (also called principals and school leaders) perceptions and experiences of school lunch. The main theoretical base is based on Henri Lefebvre’s theoretical framework of social production of space, applied mostly in Papers 2-4, together with an overarching conceptual framework of social constructivism, applied mostly in Paper 1. The thesis is based on a qualitative descriptive research design where the empirical part of the study is based on focus group discussions, empathy-based stories, a qualitative analysis of open comments from a questionnaire and in the fourth paper, individual interviews.Through the four papers performed within this thesis it is clear that the normative, social, emotional, physical and organizational dimensions are central to the way that school lunch is experienced and perceived. The results show that pupils, teachers and head teachers share the perception of school lunch as a space for socializing and eating. The results further show that the perceptions and experiences of school lunch are negatively affected by the way the school lunch is framed and organized at both school and municipality level, and that favorable conditions for the school lunch situation do not always exist. The main concerns are centered on the meal environment, time-restrictions, the logistics and the different structures that pupils, teachers and head teachers have to adapt to. These challenges may affect the possibility of influencing practices and adherence to policies. The physical and organizational dimensions of school lunch need to be acknowledged: specifically, time management and the extent to which school restaurants are purposively designed and built. This is something that should be also taken in consideration when designing and building new school restaurants.
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33.
  • Berggren, Linda, et al. (author)
  • Nordic children's conceptualizations of healthy eating in relation to school lunch
  • 2017
  • In: Health Education. - : Emerald Group Publishing Limited. - 0965-4283 .- 1758-714X. ; 117:2, s. 130-147
  • Journal article (peer-reviewed)abstract
    • Purpose: Pupils' perspective should be better taken into account when developing nutrition education at school. The purpose of this paper is to explore Nordic children's perspectives on the healthiness of meals in the context of school lunches.Design/methodology/approach: In total, 78 focus group discussions were conducted with 10-11-year-old girls and boys (n=457) from schools in Finland, Iceland, Norway and Sweden, which were participating in the Nordic school meal project ProMeal during the school year 2013-2014. A flexible discussion guide and stimulus material in the form of 14 photographs displaying different school lunch contexts were used. The discussions were analyzed using thematic analysis.Findings: These Nordic children seem to share the adult-set aim of healthy eating in the school context as a socio-cultural norm. Although healthy eating was constructed as a rational, normative and acceptable way to eat at school, unhealthy eating was emphasized as negotiably acceptable when eaten occasionally and under certain circumstances (e.g. at special occasions). Unhealthy eating also comprised emotionally laden descriptions such as enjoyment and disgust. Practical implications: Children's conceptualizations of healthy eating are connected to nutritional, socio-cultural, emotional and normative dimensions, which should be reflected also when developing nutrition education in school.Originality/value: The need for research exploring children's experiences of, and understandings about, school lunch motivated this unique multicenter study with a large number of participating children. In the focus groups a child-oriented, photo-elicitation method was used.
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34.
  • Berggren, Linda, et al. (author)
  • Perspectives about health outcomes related to food among Nordic children
  • 2016
  • Conference paper (peer-reviewed)abstract
    • Perspectives about health outcomes related to food among Nordic childrenLinda Berggren* 1, Sanna Talvia2, Eldbjørg Fossgard3, Unnur Björk Arnfjörð4, Agneta Hörnell 1, Anna Ólafsdóttir 4,Ingibjörg Gunnarsdóttir 5, Hege Wergedahl 3, Hanna Lagström 6, Maria Waling1, Cecilia Olsson11Umeå University, Department of food and nutrition, Umeå, Sweden, 2Child and Youth Research institute, Turku, Finland,3Faculty of Education, Bergen University College, Bergren, Norway, 4School of Education, University of Iceland, 5TheNational University Hospital of Iceland , Unit for Nutrition Research, Reykjavik, Iceland, 6University of Turku, TurkuInstitute of Child and Youth Research, Turku, FinlandPreferred presentation type: Only PosterBackground and aims: Dietary intake in school has previously been studied but little is known about Nordic children’sperspectives on food healthiness in the school lunch context. This study aims to explore 10-year-old Nordic children’sperspectives on outcomes of healthy eating in the school lunch context.Methods: Seventy-two focus groups were conducted in Sweden, Finland, Norway and Iceland with a total of 423participants. A flexible topic guide and 14 preselected photos displaying different school lunch contexts were used asstimuli material. Interviews were transcribed and analyzed using thematic analysis.Results: Children reasoned that school lunch are and should be healthy since the food eaten at school has short andlong term outcomes related to cognitive and physical health. It was commonly expressed that food eaten in school affectsschool work and functioning in learning activities. It was also stated that food eaten in school can have negative andpositive effects on your mood, e.g. eating unhealthy food or an insufficient amount of food, puts you in a bad mood whichcan affect the rest of the school day. The discussions mainly relied on negative short term effects such as feeling ill andreduced stamina. Some food and food groups such as vegetables, milk and fish, were mentioned in a more positivesense highlighting the positive short- and long term outcomes on health. When describing the long-term outcomes ofeating, children mentioned that healthy eating helps to build muscles, grow and prevent diseases, such as cancer anddiabetes. Sugar and fat was frequently mentioned as being the cause of overweight and some other diseases.Conclusion: In general, Nordic children have an adequate understanding of established relations between food andhealth. Yet, we know that many pupils do not eat according to recommendations. This highlights the importance of takingthe complexity of food choice into consideration in nutritional education.Disclosure of Interest: None to declare
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35.
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36.
  • Berggren, Linda, et al. (author)
  • The lived experiences of school lunch : an empathy-based study with children in Sweden
  • 2020
  • In: Children's Geographies. - : Routledge. - 1473-3285 .- 1473-3277. ; 18:3, s. 339-350
  • Journal article (peer-reviewed)abstract
    • School lunch is in general regulated through policies and agendas constituted by the perspectives of adults. In this article, we focus on children’s lived experiences of school lunch with a special emphasis on emotions and how they relate to social and physical dimensions. This study draws on empathy-based stories written by 10–11 year olds (n = 171) from schools in Sweden. We identified three themes: Interaction and exposure, Routines and restrictions and Food and eating. The children’s lived experiences of school lunch and the emotions attached to them are closely associated and intertwined with the socio-spatial dimension of school lunch. A pleasant meal experience seems to require harmonization between the physical and social space whilst negative experiences contain tensions between them, something that actors working with school lunch and school lunch environments should take in consideration when resourcing, planning and scheduling school lunch, and also when designing new school restaurants.
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37.
  • Bergkvist, Linda, 1979- (author)
  • Towards a Framework for Relational-Oriented Management of Information Systems Outsourcing : Key Conditions Connected to Actors, Relationships and Process
  • 2014
  • Doctoral thesis (other academic/artistic)abstract
    • Currently, client and supplier firms are struggling with how they can make their information systems (IS) outsourcing engagements more valuable. This research points to the importance of successful practice and outcome in IS outsourcing for achieving engagements of value. To enhance the understanding of IS out­sourcing over time, a process perspective is applied. Further, this research is based on the contention that IS outsourcing is more likely to be successful if challenges are managed in a proactive manner and with a relationship perspective. Thus, understanding challenges in IS outsourcing requires a symmetric view on client and supplier.The thesis is based on two studies presented as three steps of research: development, validation and reconsideration of a conceptual framework. The licentiate study centred on the step of development whereas the present doctoral study has a focus on the steps of validation and reconsideration. The purpose of this study includes investigating how the management of successful practice and outcome in IS outsourcing can be enabled. To address the purpose, the IS outsourcing process is studied in a client–supplier relationship. This includes that different actor perspectives, including strategic, operative, and systems, are considered for a better understanding of the practice of IS outsourcing, the challenges, and how different actors convey successful IS outsourcing.The thesis contributes a framework for relational-oriented management of IS outsourcing, which provides the structure for understanding what needs to be managed in terms of key conditions, when and how in connection to actors, relationships, and process. Theoretical propositions, enhancing the understanding of the complexity of IS outsourcing as well as the number of challenges involved, are also presented. In brief, these propositions relate to the circumstance that IS outsourcing requires management on different levels and with different kinds of results in mind.
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38.
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39.
  • Bergvall, Niklas, et al. (author)
  • Upgrading of fast pyrolysis bio-oils to renewable hydrocarbons using slurry- and fixed bed hydroprocessing
  • 2024
  • In: Fuel processing technology. - : Elsevier B.V.. - 0378-3820 .- 1873-7188. ; 253
  • Journal article (peer-reviewed)abstract
    • Liquefaction of lignocellulosic biomass through fast pyrolysis, to yield fast pyrolysis bio-oil (FPBO), is a technique that has been extensively researched in the quest for finding alternatives to fossil feedstocks to produce fuels, chemicals, etc. Properties such as high oxygen content, acidity, and poor storage stability greatly limit the direct use of this bio-oil. Furthermore, high coking tendencies make upgrading of the FPBO by hydrodeoxygenation in fixed-bed bed hydrotreaters challenging due to plugging and catalyst deactivation. This study investigates a novel two-step hydroprocessing concept; a continuous slurry-based process using a dispersed NiMo-catalyst, followed by a fixed bed process using a supported NiMo-catalyst. The oil product from the slurry-process, having a reduced oxygen content (15 wt%) compared to the FPBO and a comparatively low coking tendency (TGA residue of 1.4 wt%), was successfully processed in the downstream fixed bed process for 58 h without any noticeable decrease in catalyst activity, or increase in pressure drop. The overall process resulted in a 29 wt% yield of deoxygenated oil product (0.5 wt% oxygen) from FPBO with an overall carbon recovery of 68%.
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40.
  • Biloglav, Andrea, et al. (author)
  • SFPQ-ABL1-positive B-cell precursor acute lymphoblastic leukemias
  • 2020
  • In: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264.
  • Journal article (peer-reviewed)abstract
    • In recent years, a subgroup of B‐cell precursor acute lymphoblastic leukemia (BCP ALL) without an established abnormality (“B‐other”) has been shown to be characterized by rearrangements of ABL1 , ABL2 , CSF1R , or PDGFRB (a.k.a. ABL‐class genes). Using FISH with probes for these genes, we screened 55 pediatric and 50 adult B‐other cases. Three (6%) of the adult but none of the childhood B‐other cases were positive for ABL‐class aberrations. RT‐PCR and sequencing confirmed a rare SFPQ‐ABL1 fusion in one adult B‐other case with t(1;9)(p34;q34). Only six SFPQ ‐ABL1 ‐positive BCP ALLs have been reported, present case included. A review of these shows that all harbored fusions between exon 9 of SFPQ and exon 4 of ABL1 , that the fusion is typically found in adolescents/younger adults without hyperleukocytosis, and that IKZF1 deletions are recurrent. The few patients not treated with tyrosine kinase inhibitors (TKIs) and/or allogeneic stem cell transplantation relapsed, strengthening the notion that TKI should be added to the therapy of SFPQ ‐ABL1 ‐positive BCP ALL.
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41.
  • Björnsson, Bergthor, et al. (author)
  • Nitrite, a novel method to decrease ischemia/reperfusion injury in the rat liver
  • 2015
  • In: World Journal of Gastroenterology. - : Baishideng Publishing Group Co. Limited. - 1007-9327 .- 2219-2840. ; 21:6, s. 1775-1783
  • Journal article (peer-reviewed)abstract
    • AIM: To investigate whether nitrite administered prior to ischemia/reperfusion (I/R) reduces liver injury.METHODS: Thirty-six male Sprague-Dawley rats were randomized to 3 groups, including sham operated (n = 8), 45-min segmental ischemia of the left liver lobe (IR, n = 14) and ischemia/reperfusion (I/R) preceded by the administration of 480 nmol of nitrite (n = 14). Serum transaminases were measured after 4 h of reperfusion. Liver microdialysate (MD) was sampled in 30-min intervals and analyzed for glucose, lactate, pyruvate and glycerol as well as the total nitrite and nitrate (NOx). The NOx was measured in serum.RESULTS: Aspartate aminotransferase (AST) at the end of reperfusion was higher in the IR group than in the nitrite group (40 ± 6.8 μkat/L vs 22 ± 2.6 μkat/L, P = 0.022). Similarly, alanine aminotransferase (ALT) was also higher in the I/R group than in the nitrite group (34 ± 6 μkat vs 14 ± 1.5 μkat, P = 0.0045). The NOx in MD was significantly higher in the nitrite group than in the I/R group (10.1 ± 2.9 μM vs 3.2 ± 0.9 μM, P = 0.031) after the administration of nitrite. During ischemia, the levels decreased in both groups and then increased again during reperfusion. At the end of reperfusion, there was a tendency towards a higher NOx in the I/R group than in the nitrite group (11.6 ± 0.7 μM vs 9.2 ± 1.1 μM, P = 0.067). Lactate in MD was significantly higher in the IR group than in the nitrite group (3.37 ± 0.18 mM vs 2.8 ± 0.12 mM, P = 0.01) during ischemia and the first 30 min of reperfusion. During the same period, glycerol was also higher in the IRI group than in the nitrite group (464 ± 38 μM vs 367 ± 31 μM, P = 0.049). With respect to histology, there were more signs of tissue damage in the I/R group than in the nitrite group, and 29% of the animals in the I/R group exhibited necrosis compared with none in the nitrite group. Inducible nitric oxide synthase (iNOS) transcription increased between early ischemia (t = 15) and the end of reperfusion in both groups.CONCLUSION: Nitrite administered before liver ischemia in the rat liver reduces anaerobic metabolism and cell necrosis, which could be important in the clinical setting.
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42.
  • Björnsson, Bergthor, et al. (author)
  • Remote or Conventional Ischemic Preconditioning -Local Liver Metabolism in Rats Studied with Microdialysis
  • 2012
  • In: Journal of Surgical Research. - : Elsevier. - 0022-4804 .- 1095-8673. ; 176:1, s. 55-62
  • Journal article (peer-reviewed)abstract
    • Background. Ischemic preconditioning (IPC) of the liver decreases liver injury secondary to ischemia and reperfusion. An attractive alternative to IPC is remote ischemic preconditioning (R-IPC), but these two methods have not previously been compared. Material and Methods. Eighty-seven rats were randomized into four groups: sham operated (n = 15), 1 h segmental ischemia (IRI, n = 24), preceeded by IPC (n = 24), or R-IPC (n = 24) (to the left hindleg). IPC and R-IPC were performed with 10 min ischemia and 10 min of reperfusion. Analyses of liver microdialysate (MD), serum transaminase levels, and liver histology were made. Results. Rats treated with IPC and R-IPC had significantly lower AST, 71.5 (19.6) IU/L respective 96.6 (12.4) at 4 h reperfusion than those subjected to IRI alone, 155 (20.9), P = 0.0004 and P = 0.04 respectively. IPC also had lower ALT levels, 41.6 (11.3) IU/L than had IRI 107.4 (15.5), P = 0.003. The MD glycerol was significantly higher during ischemia in the R-IPC = 759 (84) mu M] and the IRI = 732 (67)] groups than in the IPC 514 (70) group, P = 0.022 and P = 0.046 respectively. The MD glucose after ischemia was lower in the IPC group 7.1 (1.2) than in the IRI group 12.7 (1.6), P = 0.005. Preconditioning to the liver caused an direct increase in lactate, glucose and glycerol in the ischemic segment compared with the control segment an effect not seen in the R-IPC and IRI groups. Conclusions. IPC affects glucose metabolism in the rat liver, observed with MD. IPC reduces liver cell injury during ischemic and reperfusion in rats. R-IPC performed over the same length of time as IPC does not have the same effect as the latter on ALT levels and MD glycerol; this may suggest that R-IPC does not offer the same protection as IPC in this setting of rat liver IRI.
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43.
  • Blockhuys, Stephanie, 1983, et al. (author)
  • Evaluation of ATOX1 as a potential predictive biomarker for tetrathiomolybdate treatment of breast cancer patients with high risk of recurrence
  • 2021
  • In: Biomedicines. - : MDPI AG. - 2227-9059. ; 9:12
  • Journal article (peer-reviewed)abstract
    • Copper plays a key role in cancer metastasis, which is the most common cause of cancer death. Copper depletion treatment with tetrathiomolybdate (TM) improved disease-free survival in breast cancer patients with high risk of recurrence in a phase II clinical trial. Because the copper metallochaperone ATOX1 was recently reported to drive breast cancer cell migration and breast cancer migration is a critical factor in metastasis, we tested if ATOX1 expression levels in primary tumor tissue could predict the TM treatment outcome of breast cancer patients at high risk of recurrence. We performed ATOX1 immunohistochemical staining of breast tumor material (before TM treatment) of 47 patients enrolled in the phase II TM clinical trial and evaluated ATOX1 expression levels in relation with patient outcome after TM treatment. Our results show that higher ATOX1 levels in the tumor cell cytoplasm correlate with a trend towards better event-free survival after TM treatment for triple-negative breast cancer patients and patients at stage III of disease. In conclusion, ATOX1 may be a potential predictive biomarker for TM treatment of breast cancer patients at high risk of recurrence and should be tested in a larger cohort of patients.
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44.
  • Bojmar, Linda, et al. (author)
  • miR-18a is regulated between progressive compartments of cancers, and incorporated in exosomes with the potential of creating premetastatic niches and predict cancer outcome
  • 2015
  • Other publication (other academic/artistic)abstract
    • The ultimate cause of death for many cancer patients is the spread of the cancer via metastasis. Even so, there are still a lack of knowledge regarding the metastasis process. This study was performed to investigate the role of metastamirs in exosomes and their metastatic patterns. We used the well-established isogeneic murine cancer model of low metastatic 67NR cells, mimicking luminal/basal breast tumors, and highly metastatic 4T1 cells with characteristics of basal breast  tumors. We studied the exosomal properties and pre-metastatic effects in this metastasis model and compared human materials and exosomes of several other tumor types. Our data clearly demonstrated that exosomes from the highly metastatic cells home to the metastatic organs of their parental cells whereas exosomes from cells with low metastatic potential mostly located to lymph nodes. The exosome protein cargos also resembled their parental cells and potentially affects their target organs, and cells, differently. Furthermore, the exosomes from the highly metastatic cells had a more pronounced effect on tumor growth and pre-metastatic changes than the low metastatic exosomes. The microRNA-18a, a predictor of metastasis, was present to a higher extent in metastatic exosomes as compared to low metastatic exosomes, and altered the tumor progressive properties. Our findings support the role of exomirs as important players in the metastatic process, the value as biomarkers and potential therapeutic targets.
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45.
  • Bojmar, Linda, et al. (author)
  • The Role of MicroRNA-200 in Progression of Human Colorectal and Breast Cancer
  • 2013
  • In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:12, s. 84815-
  • Journal article (peer-reviewed)abstract
    • The role of the epithelial-mesenchymal transition (EMT) in cancer has been studied extensively in vitro, but involvement of the EMT in tumorigenesis in vivo is largely unknown. We investigated the potential of microRNAs as clinical markers and analyzed participation of the EMT-associated microRNA-200 ZEB E-cadherin pathway in cancer progression. Expression of the microRNA-200 family was quantified by real-time RT-PCR analysis of fresh-frozen and microdissected formalin-fixed paraffin-embedded primary colorectal tumors, normal colon mucosa, and matched liver metastases. MicroRNA expression was validated by in situ hybridization and after in vitro culture of the malignant cells. To assess EMT as a predictive marker, factors considered relevant in colorectal cancer were investigated in 98 primary breast tumors from a treatment-randomized study. Associations between the studied EMTmarkers were found in primary breast tumors and in colorectal liver metastases. MicroRNA-200 expression in epithelial cells was lower in malignant mucosa than in normal mucosa, and was also decreased in metastatic compared to non-metastatic colorectal cancer. Low microRNA-200 expression in colorectal liver metastases was associated with bad prognosis. In breast cancer, low levels of microRNA-200 were related to reduced survival and high expression of microRNA-200 was predictive of benefit from radiotheraphy. MicroRNA-200 was associated with ER positive status, and inversely correlated to HER2 and overactivation of the PI3K/AKT pathway, that was associated with high ZEB1 mRNA expression. Our findings suggest that the stability of microRNAs makes them suitable as clinical markers and that the EMT-related microRNA-200 - ZEB - E-cadherin signaling pathway is connected to established clinical characteristics and can give useful prognostic and treatment-predictive information in progressive breast and colorectal cancers.
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46.
  • Bolton, Kelly L., et al. (author)
  • Association Between BRCA1 and BRCA2 Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer
  • 2012
  • In: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598. ; 307:4, s. 382-390
  • Journal article (peer-reviewed)abstract
    • Context Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear. Objective To characterize the survival of BRCA carriers with EOC compared with noncarriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns. Design, Setting, and Participants A pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1213 EOC cases with pathogenic germline mutations in BRCA1 (n=909) or BRCA2 (n=304) and from 2666 noncarriers recruited and followed up at variable times between 1987 and 2010 (the median year of diagnosis was 1998). Main Outcome Measure Five-year overall mortality. Results The 5-year overall survival was 36% (95% CI, 34%-38%) for noncarriers, 44% (95% CI, 40%-48%) for BRCA1 carriers, and 52% (95% CI, 46%-58%) for BRCA2 carriers. After adjusting for study and year of diagnosis, BRCA1 and BRCA2 mutation carriers showed a more favorable survival than noncarriers (for BRCA1: hazard ratio [HR], 0.78; 95% CI, 0.68-0.89; P<.001; and for BRCA2: HR, 0.61; 95% CI, 0.50-0.76; P<.001). These survival differences remained after additional adjustment for stage, grade, histology, and age at diagnosis (for BRCA1: HR, 0.73; 95% CI, 0.64-0.84; P<.001; and for BRCA2: HR, 0.49; 95% CI, 0.39-0.61; P<.001). The BRCA1 HR estimate was significantly different from the HR estimated in the adjusted model (P for heterogeneity=.003). Conclusion Among patients with invasive EOC, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis. JAMA. 2012;307(4):382-390
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47.
  • Brandén, Jennie, et al. (author)
  • Patrullering för trygghet : vakter, nattvandrare och medborgargarden
  • 2020
  • In: (O)tryggt?. - : Premiss förlag. - 9789189077157 ; , s. 75-98
  • Book chapter (other academic/artistic)abstract
    • Under de senaste åren har frågor om trygghet tagit allt mer plats i det offentliga samtalet. Det kan handla om att otryggheten breder ut sig, att den måste bekämpas och att vi måste kunna vara trygga på gator och torg. Vissa grupper pekas ut som mer otrygga medan andra blir de som står för otryggheten. Vid en närmare granskning blir det dock tydligt att trygghet är mer komplicerat än så. Att det som är tryggt för vissa kan vara otryggt för andra. Att talet om trygghet kan betyda både hårdare straff och en längtan efter ett eget hem. Denna bok består av två delar som tillsammans tar sig an (o)trygghet från olika perspektiv samhälleliga föreställningar, politiska förändringar och ambitioner att arbeta för förändring. Bokens författare har sin hemvist i olika akademiska discipliner etnologi, folkhälsovetenskap, genusvetenskap, konstvetenskap, kulturgeografi, socialt arbete, statsvetenskap och urbana studier och ger därmed en mångfacetterad bild av vad (o)trygghet betyder i dagens Sverige. I kapitlet "Patrullering för trygghet - vakter, nattvandrare och medborgargarden" undersöks mediebeskrivningar och offentliga policydokument kopplat till tre olika former av patrullering för trygghet: privata trygghetsvakters patrullering i kommunal regi, ideella aktörers nattvandring samt högernationalistiska medborgargardens patrullering. Analysen utgår ifrån en förståelse av patrullering som ett görande, en praktik, som bidrar till att forma betydelsen av såväl trygghet som otrygghet. Syftet är att belysa frågor om vems trygghet som ska upprättas eller bevaras, hur detta ska göras, samt vad eller vilka som anses vara orsaker till otrygghet. 
  •  
48.
  • Bratteby Tollerz, Linda U, et al. (author)
  • Reliability of energy cost calculations in children with cerebral palsy, cystic fibrosis and healthy controls
  • 2011
  • In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 100:12, s. 1616-1620
  • Journal article (peer-reviewed)abstract
    • Aim: To study test-retest reliability of physiological cost index (PCI) and total cost index (TCI) in three groups of children. TCI modified PCI by excluding rest heart rate in calculation. Methods: Energy cost was evaluated from two consecutive walking tests, and results were compared between methods, tests and groups. Thirty-nine children, eight with cerebral palsy, 11 with cystic fibrosis and 20 healthy controls, aged 5-16 years participated in the study conducted at the Clinical Nutrition and Metabolism laboratory, University Hospital, Uppsala, Sweden. Heart rate was recorded during sitting and walking at self-selected speed. PCI and TCI were calculated using both non-steady-state and steady-state work heart rates. Test-retest reliability was analysed by mean of differences, pooled SD, coefficient of variation (CV%) and correlation coefficients. Results: Reliability was high for PCI and TCI. TCI showed consistently lower variation between tests than PCI for all groups. In the group with cerebral palsy, using non-steady-state showed highest reliability. Conclusion: Both PCI and TCI were reliable methods when calculating energy cost in children with cerebral palsy, cystic fibrosis and controls. TCI seemed to be a suitable alternative in the evaluation of gait efficiency in children.
  •  
49.
  • Bridel, Claire, et al. (author)
  • Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
  • 2019
  • In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
  • Research review (peer-reviewed)abstract
    • Importance  Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives  To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources  PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection  Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis  Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure  The cNfL levels adjusted for age and sex across diagnoses.Results  Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance  These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
  •  
50.
  • Buchbinder, David, et al. (author)
  • Predictors of Loss to Follow-Up Among Pediatric and Adult Hematopoietic Cell Transplantation Survivors : A Report from the Center for International Blood and Marrow Transplant Research
  • 2020
  • In: Biology of blood and marrow transplantation. - : Elsevier. - 1083-8791 .- 1523-6536. ; 26:3, s. 553-561
  • Journal article (peer-reviewed)abstract
    • Follow-up is integral for hematopoietic cell transplantation (HCT) care to ensure surveillance and intervention for complications. We characterized the incidence of and predictors for being lost to follow-up. Two-year survivors of first allogeneic HCT (10,367 adults and 3865 children) or autologous HCT (7291 adults and 467 children) for malignant/nonmalignant disorders between 2002 and 2013 reported to the Center for International Blood and Marrow Transplant Research were selected. The cumulative incidence of being lost to follow-up (defined as having missed 2 consecutive follow-up reporting periods) was calculated. Marginal Cox models (adjusted for center effect) were fit to evaluate predictors. The 10-year cumulative incidence of being lost to follow-up was 13% (95% confidence interval [CI], 12% to 14%) in adult allogeneic HCT survivors, 15% (95% CI, 14% to 16%) in adult autologous HCT survivors, 25% (95% CI, 24% to 27%) in pediatric allogeneic HCT survivors, and 24% (95% CI, 20% to 29%) in pediatric autologous HCT survivors. Factors associated with being lost to follow-up include younger age, nonmalignant disease, public/no insurance (reference: private), residence farther from the tranplantation center, and being unmarried in adult allogeneic HCT survivors; older age and testicular/germ cell tumor (reference: non-Hodgkin lymphoma) in adult autologous HCT survivors; older age, public/no insurance (reference: private), and nonmalignant disease in pediatric allogeneic HCT survivors; and older age in pediatric autologous HCT survivors. Follow-up focusing on minimizing attrition in high-risk groups is needed to ensure surveillance for late effects.
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