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1.
  • Wang, Zhaoming, et al. (författare)
  • Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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2.
  • Dahlin, Anna M, 1979-, et al. (författare)
  • The role of the CpG island methylator phenotype in colorectal cancer prognosis depends on microsatellite instability screening status
  • 2010
  • Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 16:6, s. 1845-1855
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: The aim of this study was to relate the CpG island methylator phenotype (CIMP; characterized by extensive promoter hypermethylation) to cancer-specific survival in colorectal cancer, taking into consideration relevant clinicopathologic factors, such as microsatellite instability (MSI) screening status and the BRAF V600E mutation. EXPERIMENTAL DESIGN: Archival tumor samples from 190 patients from the Northern Sweden Health and Disease Study (NSHDS) and 414 patients from the Colorectal Cancer in Umeå Study (CRUMS), including 574 with cancer-specific survival data, were analyzed for an eight-gene CIMP panel using quantitative real-time PCR (MethyLight). MSI screening status was assessed by immunohistochemistry. RESULTS: CIMP-low patients had a shorter cancer-specific survival compared with CIMP-negative patients (multivariate hazard ratio in NSHDS, 2.01; 95% confidence interval, 1.20-3.37; multivariate hazard ratio in CRUMS, 1.48; 95% confidence interval, 1.00-2.22). This result was similar in subgroups based on MSI screening status and was statistically significant in microsatellite stable (MSS) tumors in NSHDS. For CIMP-high patients, a shorter cancer-specific survival compared with CIMP-negative patients was observed in the MSS subgroup. Statistical significance was lost after adjusting for the BRAF mutation, but the main findings were generally unaffected. CONCLUSIONS: In this study, we found a poor prognosis in CIMP-low patients regardless of MSI screening status, and in CIMP-high patients with MSS. Although not consistently statistically significant, these results were consistent in two separate patient groups and emphasize the potential importance of CIMP and MSI status in colorectal cancer research.
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3.
  • Henriksson, Aron, et al. (författare)
  • Corpus-Driven Terminology Development : Populating Swedish SNOMED CT with Synonyms Extracted from Electronic Health Records
  • 2013
  • Ingår i: Proceedings of the 2013 Workshop on Biomedical Natural Language Processing (BioNLP 2013). - : Association for Computational Linguistics. - 9781937284541 ; , s. 36-44
  • Konferensbidrag (refereegranskat)abstract
    • The various ways in which one can refer to the same clinical concept needs to be accounted for in a semantic resource such as SNOMED CT. Developing terminological resources manually is, however, prohibitively expensive and likely to result in low coverage, especially given the high variability of language use in clinical text. To support this process, distributional methods can be employed in conjunction with a large corpus of electronic health records to extract synonym candidates for clinical terms. In this paper, we exemplify the potential of our proposed method using the Swedish version of SNOMED CT, which currently lacks synonyms. A medical expert inspects two thousand term pairs generated by two semantic spaces -- one of which models multiword terms in addition to single words -- for one hundred preferred terms of the semantic types disorder and finding.
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4.
  • Jacobs, Kevin B, et al. (författare)
  • Detectable clonal mosaicism and its relationship to aging and cancer.
  • 2012
  • Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
  • Tidskriftsartikel (refereegranskat)abstract
    • In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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5.
  • Andersson, Johanna, et al. (författare)
  • go: NEUTRAL
  • 2014
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • go: NEUTRAL är ett samarbete mellan Skanska, ÅF, Siemens, IVL Svenska Miljöinstitutet och Business Region Göteborg som syftar till att öka möjligheterna att utveckla energieffektiva och hållbara lösningar genom att få till en samverkan mellan olika aktörer i byggbranschen i ett tidigt skede. Det övergripande målet med förstudien är att börja utveckla, testa och tillämpa en modell för tidig samverkan i profilprojekt för innovativt hållbart byggande. Ett delmål är att definiera och utveckla vilka hållbarhetskriterier som ska gälla för samarbetet. Detta har utförts genom att utveckla ett koncept kring namnet go: NEUTRAL. I förstudien presenteras en preliminär utformning av mål för konceptet go: NEUTRAL bestående av ett övergripande mål och tre delmål. För att lyckas med samverkan kring hållbarhetsfrågor i byggprocessen krävs kunskap om hur man kan skapa förutsättningar för tidig samverkan. För att skaffa denna kunskap har följande sammanställningar utförts under förstudien: Kartläggning av olika aktörers motiv till tidig samverkan, Identifiering av hinder för tidig samverkan, samt Identifiering av områden som är viktiga att beakta för att skapa goda förutsättningar för tidig samverkan. Konceptet go: NEUTRAL är skapat och förutsättningar för samverkan är undersökta, men inte färdigutvecklat. Förstudiens plan för vidare arbete är uppdelad i tre områden: a) Fastställ ramar för samverkan mellan parter, b) vidareutveckla konceptet go: NEUTRAL, samt c) utveckla processen.
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6.
  • Andersson, Johanna, et al. (författare)
  • go: NEUTRAL - Förstudie
  • 2014
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Inom byggbranschen har utvecklingen av energibesparande åtgärder och byggnation med material och komponenter som leder till lägre energianvändning, klimatpåverkan och resursbesparing påskyndats genom att medvetenheten om klimatfrågans betydelse och den byggda miljöns bidrag till de totala utsläppen har ökat. Exploateringsprojekt är begränsad i budget, bygger på samverkan mellan många aktörer och genomförs under stor tidspress. I dessa projekt används ofta beprövad och etablerade tekniska lösningar, vilket medför att utrymmet för innovationer begränsas och därmed att projektets potentiella bidrag till en hållbar stadsutveckling inte utnyttjas fullt ut. För att få till en samverkan mellan olika aktörer i ett tidigit skede, och därmed öka möjlighetena att utveckla energi- och klimateffektiva samt hållbara lösningar, initierade Skanska detta projekt som gavs nament go: NETURAL. Övriga medverkande aktörer i projektet är ÅF, Siemens, Business Region Göteborg och IVL Svenska Miljöinstitutet.
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7.
  • Andersson, Ulrika, et al. (författare)
  • A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk
  • 2010
  • Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 12, s. 17-17
  • Tidskriftsartikel (refereegranskat)abstract
    • Glioma is the most common type of adult brain tumor and glioblastoma, its most aggressive form, has a dismal prognosis. Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR, ERBB2, ERBB3, ERBB4) family, and the vascular endothelial growth factor receptor (VEGFR), play a central role in tumor progression. We investigated the genetic variants of EGFR, ERBB2, VEGFR and their ligands, EGF and VEGF on glioma and glioblastoma risk. In addition, we evaluated the association of genetic variants of a newly discovered family of genes known to interact with EGFR: LRIG2 and LRIG3 with glioma and glioblastoma risk. Methods. We analyzed 191 tag single nucleotide polymorphisms (SNPs) capturing all common genetic variation of EGF, EGFR, ERBB2, LRIG2, LRIG3, VEGF and VEGFR2 genes. Material from four case-control studies with 725 glioma patients (329 of who were glioblastoma patients) and their 1 610 controls was used. Haplotype analyses were conducted using SAS/Genetics software. Results. Fourteen of the SNPs were significantly associated with glioma risk at p< 0.05, and 17 of the SNPs were significantly associated with glioblastoma risk at p< 0.05. In addition, we found that one EGFR haplotype was related to increased glioblastoma risk at p=0.009, Odds Ratio [OR] = 1.67 (95% confidence interval (CI): 1.14, 2.45). The Bonferroni correction made all p-values non-significant. One SNP, rs4947986 next to the intron/exon boundary of exon 7 in EGFR, was validated in an independent data set of 713 glioblastoma and 2 236 controls, [OR] = 1.42 (95% CI: 1.06,1.91). Discussion. Previous studies show that regulation of the EGFR pathway plays a role in glioma progression but the present study is the first to find that certain genotypes of the EGFR gene may be related to glioblastoma risk. Further studies are required to reinvestigate these findings and evaluate the functional significance.
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10.
  • Börjesson Rivera, Miriam, et al. (författare)
  • Getting there and back again : Commuting and ICT in six cities across the globe
  • 2012
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Ericsson ConsumerLab performed a qualitative exploratory study of how people experience daily commuting in three different countries. This report aims to present the outcome of the study in such a way that the data can be useful for further analyses and studies of commuting in relation to ICT use and environmental sustainability. Based on the study’s findings this report will present analytical data on: i) how ICT can be linked to everyday travel in order to facilitate commuting from the user’s point of view; and ii) how ICT solutions can enable commuting in an environmentally more sustainable way.The study, which had an ethnographic approach, showed that in general, commuters would like their commuting time to be, or at least seem, as short as possible. The respondents spend hours commuting every week and often claim to consider it a waste of time. Regardless of means of transport, they would like to get the most out of their commuting time (working, socialising, relaxing etc.), which implies that there is a demand for further technological improvements in this area (voice recognition services in cars, privacy settings in public transport, connectivity in public transport, etc.). An aspect that adds to how people perceive their commuting time concerns the extent to which its duration is predictable – even if the time cannot be shortened, commuters at least want to know how much time they will spend on their daily commute, so that they can plan their day with more certainty.Irrespective of means of transport, two major frustrations for commuters are lack of flow and the presence and behaviour of other people. People seem to lack good real-time information enabling them to avoid interruptions in their commute and much of their frustration relates to poor infrastructure conditions and management. Frustration with other people derives from their conduct in traffic contributing to inconveniences, congestion or hazards, or from noise, smell or littering on public transport.The greatest motivators for commuting by car are a feeling of independence in relation to other people, schedule and choice of route, and the private space the car offers. This means that the car provides flexibility in terms of when and how people travel, while also providing a private space both mentally (“in the car you can do whatever you want”) and physically (“you don’t have to hustle with others on the bus or train”). The major frustration when commuting by car is the need to focus on driving, so drivers cannot utilise time as they would wish.People generally justify their choice of public transport by anti-car arguments, which include difficulty in finding a parking space at work, expensive parking, fear of driving, lack of driving licence etc., but can also motivate their choice as giving them ‘me-time’ without having to focus on driving. The major frustration with commuting by public transport is dependency on time schedules and the shortcomings of the public transport network. This is exacerbated by a lack of relevant information or available options. However, commuting can be improved in a variety of ways for car and public transport users with the help of ICT. From a sustainability perspective, it is important to exploit the potential of ICT solutions to facilitate more environmentally friendly practices.Many of the ICT (Information Communication Technology) solutions identified in this report require reliable access to the internet and/or mobile phone network. The mobile phone is currently the single most important internet device while commuting, thus perhaps being the point of departure for many of the solutions, such as travel planner, ticketing options, etc, but for car users mobile phone services need to be adapted through better in-car voice recognition technologies, since the focus needs to be on driving. Current information services could be more personalised and contextualised in order to better suit the individual driver and most of these ICT solutions and services are also applicable to public transport commuters, but an additional function for such commuters could be some kind of ‘emergency button’ on mobile phones to increase their sense of security in travel.Home office solutions are a way of avoiding the frustrations of commuting altogether. While working from home is regarded by some with ambivalence and is impossible for many, there are ways of refining these solutions.
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11.
  • Cederberg, Christel, et al. (författare)
  • An LCA researcher's wish list-data and emission models needed to improve LCA studies of animal production.
  • 2013
  • Ingår i: Animal. - 1751-7311 .- 1751-732X. ; 7:Suppl 2, s. 212-219
  • Tidskriftsartikel (refereegranskat)abstract
    • The last decade has seen an increase in environmental systems analysis of livestock production, resulting in a significant number of studies with a holistic approach often based on life-cycle assessment (LCA) methodology. The growing public interest in global warming has added to this development; guidelines for carbon footprint (CF) accounting have been developed, including for greenhouse gas (GHG) accounting of animal products. Here we give an overview of methods for estimating GHG emissions, with emphasis on nitrous oxide, methane and carbon from land use change, presently used in LCA/CF studies of animal products. We discuss where methods and data availability for GHGs and nitrogen (N) compounds most urgently need to be improved in order to produce more accurate environmental assessments of livestock production. We conclude that the top priority is to improve models for N fluxes and emissions from soils and to implement soil carbon change models in LCA/CF studies of animal products. We also point at the need for more farm data and studies measuring emissions from soils, manure and livestock in developing countries.
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12.
  • Dahlin, Anna M, 1979-, et al. (författare)
  • Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor
  • 2011
  • Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 24, s. 671-682
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to relate the density of tumor infiltrating T cells to cancer-specific survival in colorectal cancer, taking into consideration the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) screening status. The T-cell marker CD3 was stained by immunohistochemistry in 484 archival tumor tissue samples. T-cell density was semiquantitatively estimated and scored 1-4 in the tumor front and center (T cells in stroma), and intraepithelially (T cells infiltrating tumor cell nests). Total CD3 score was calculated as the sum of the three CD3 scores (range 3-12). MSI screening status was assessed by immunohistochemistry. CIMP status was determined by quantitative real-time PCR (MethyLight) using an eight-gene panel. We found that patients whose tumors were highly infiltrated by T cells (total CD3 score ≥7) had longer survival compared with patients with poorly infiltrated tumors (total CD3 score ≤4). This finding was statistically significant in multivariate analyses (multivariate hazard ratio, 0.57; 95% confidence interval, 0.31-1.00). Importantly, the finding was consistent in rectal cancer patients treated with preoperative radiotherapy. Although microsatellite unstable tumor patients are generally considered to have better prognosis, we found no difference in survival between microsatellite unstable and microsatellite stable (MSS) colorectal cancer patients with similar total CD3 scores. Patients with MSS tumors highly infiltrated by T cells had better prognosis compared with intermediately or poorly infiltrated microsatellite unstable tumors (log rank P=0.013). Regarding CIMP status, CIMP-low was associated with particularly poor prognosis in patients with poorly infiltrated tumors (multivariate hazard ratio for CIMP-low versus CIMP-negative, 3.07; 95% confidence interval, 1.53-6.15). However, some subset analyses suffered from low power and are in need of confirmation by independent studies. In conclusion, patients whose tumors are highly infiltrated by T cells have a beneficial prognosis, regardless of MSI, whereas the role of CIMP status in this context is less clear.
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13.
  • Dahlin, Anna, 1979- (författare)
  • The CpG island methylator phenotype in colorectal cancer : studies on risk and prognosis
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background Colorectal cancer (CRC) is the second most common malignancy in developed countries. The mortality is high, with nearly half of patients dying from the disease. The primary treatment of CRC is surgery, and decisions about additional treatment with chemotherapy are based mainly on tumor stage. Novel prognostic markers that identify patients at high risk of recurrence and cancer-related death are needed. The development of CRC has been described in terms of two different pathways; the microsatellite instability (MSI) and chromosomal instability (microsatellite stable, MSS) pathway. More recently, the CpG island methylator phenotype (CIMP), characterized by frequent DNA hypermethylation, has been described as an alternative pathway of tumorigenesis. The event of DNA methylation is dependent on one-carbon metabolism, in which folate and vitamin B12 have essential functions. The purpose of this thesis was to study CIMP in CRC. The specific aims were to investigate the potential role of components of one-carbon metabolism as risk factors for this subgroup of tumors, and the prognostic importance of CIMP status, taking into consideration important confounding factors, such as MSI and tumor-infiltrating T cells. Methods CRC cases and referents included in the Northern Sweden Health and Disease Study (NSHDS, 226 cases and 437 referents) and CRC cases in the Colorectal Cancer in Umeå Study (CRUMS, n=490) were studied. Prediagnostic plasma concentrations of folate and vitamin B12 were analyzed in NSHDS. In both study groups, CIMP status was determined in archival tumor tissue by real-time quantitative PCR using an eight-gene panel (CDKN2A, MLH1, CACNA1G, NEUROG1, RUNX3, SOCS1, IGF2 and CRABP1). MSI screening status and the density of tumor-infiltrating T cells were determined by immunohistochemistry.  Results An inverse association was found between plasma concentrations of vitamin B12 and rectal, but not colon, cancer risk. We also found a reduced risk of CIMP-high and CIMP-low CRC in study subjects with the lowest levels of plasma folate. We found that patients with CIMP-low tumors in both NSHDS and CRUMS had a poorer prognosis compared with CIMP-negative, regardless of MSI screening status. We also found that MSS CIMP-high patients had a poorer prognosis compared with MSS CIMP-negative. The density of tumor-infiltrating T cells and CIMP status were both found to be independent predictors of CRC patient prognosis. A particularly poor prognosis was found in patients with CIMP-low tumors poorly infiltrated by T cells. In addition, the density of T cells appeared to be more important than MSI screening status for predicting CRC patient prognosis. Conclusion Rather than being one disease, CRC is a heterogeneous set of diseases with respect to clinico-pathological and molecular characteristics. We found that the association between risk and plasma concentration of vitamin B12 and folate depends on tumor site and CIMP status, respectively. Patient prognosis was found to be different depending on CIMP and MSI screening status, and the density of tumor-infiltrating T cells.
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14.
  • Dalianis, Hercules, et al. (författare)
  • Stockholm EPR Corpus : A Clinical Database Used to Improve Health Care
  • 2012
  • Ingår i: Proceedings of SLCT 2012. ; , s. 17-18
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The care of patients is well documented in health records. Despite being a valuable source of information that could be mined by computers and used to improve health care, health records are not readily available for research. Moreover, the narrative parts of the records are noisy and need to be interpreted by domain experts. In this abstract we describe our experiences of gaining access to a database of electronic health records for research. We also highlight some important issues in this domain and describe a number of possible applications, including comorbidity networks, detection of hospital-acquired infections and adverse drug reactions, as well as diagnosis coding support.
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15.
  • Dobbins, Sara E., et al. (författare)
  • Common variation at 10p12.31 near MLLT10 influences meningioma risk
  • 2011
  • Ingår i: Nature Genetics. - London : Nature America, Inc.. - 1061-4036 .- 1546-1718. ; 43:9, s. 825-827
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 x 10(-14)). This finding advances our understanding of the genetic basis of meningioma development.
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16.
  • Finnveden, Göran, et al. (författare)
  • Policy instruments towards a sustainable waste management
  • 2013
  • Ingår i: Sustainability. - Basel : MDPI AG. - 2071-1050. ; 5:3, s. 841-881
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this paper is to suggest and discuss policy instruments that could lead towards a more sustainable waste management. The paper is based on evaluations from a large scale multi-disciplinary Swedish research program. The evaluations focus on environmental and economic impacts as well as social acceptance. The focus is on the Swedish waste management system but the results should be relevant also for other countries. Through the assessments and lessons learned during the research program we conclude that several policy instruments can be effective and possible to implement. Particularly, we put forward the following policy instruments: “Information”; “Compulsory recycling of recyclable materials”; “Weight-based waste fee in combination with information and developed recycling systems”; “Mandatory labeling of products containing hazardous chemicals”, “Advertisements on request only and other waste minimization measures”; and “Differentiated VAT and subsidies for some services”. Compulsory recycling of recyclable materials is the policy instrument that has the largest potential for decreasing the environmental impacts with the configurations studied here. The effects of the other policy instruments studied may be more limited and they typically need to be implemented in combination in order to have more significant impacts. Furthermore, policy makers need to take into account market and international aspects when implementing new instruments. In the more long term perspective, the above set of policy instruments may also need to be complemented with more transformational policy instruments that can significantly decrease the generation of waste.
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17.
  • Finnveden, Göran, 1961-, et al. (författare)
  • Regeringen måste satsa på resurseffektivt samhälle
  • 2013
  • Ingår i: Dagens nyheter. - : AB Dagens nyheter. - 1101-2447. ; :2013-04-01
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Regeringen förbereder en avfallspolitisk proposition. Den kommer förhoppningsvis att klargöra vem som ska ha ansvaret att samla in våra förpackningar. Men fokus borde också ligga på hur vi kan gå mot ett samhälle där resurser används så effektivt som möjligt, skriver forskare på miljöområdet.
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18.
  • Flysjö, A., et al. (författare)
  • How does co-product handling affect the carbon footprint of milk? Case study of milk production in New Zealand and Sweden
  • 2011
  • Ingår i: International Journal of Life Cycle Assessment. - : Springer Science and Business Media LLC. - 1614-7502 .- 0948-3349. ; 16:5, s. 420-430
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose This paper investigates different methodologies of handling co-products in life cycle assessment (LCA) or carbon footprint (CF) studies. Co-product handling can have a significant effect on final LCA/CF results, and although there are guidelines on the preferred order for different methods for handling co-products, no agreed understanding on applicable methods is available. In the present study, the greenhouse gases (GHG) associated with the production of 1 kg of energy-corrected milk (ECM) at farm gate is investigated considering co-product handling. Materials and methods Two different milk production systems were used as case studies in the investigation of the effect of applying different methodologies in coproduct handling: (1) outdoor grazing system in New Zealand and (2) mainly indoor housing system with a pronounced share of concentrate feed in Sweden. Since the cows produce milk, meat (when slaughtered), calves, manure, hides, etc., the environmental burden (here GHG emissions) must be distributed between these outputs (in the present study no emissions are attributed to hides specifically, or to manure which is recycled on-farm). Different methodologically approaches, (1) system expansion (two cases), (2) physical causality allocation, (3) economic allocation, (4) protein allocation and (5) mass allocation, are applied in the study. Results and discussion The results show large differences in the final CF number depending on which methodology has been used for accounting co-products. Most evident is that system expansion gives a lower CF for milk than allocation methods. System expansion resulted in 63- 76% of GHG emissions attributed directly to milk, while allocation resulted in 85-98%. It is stressed that meat is an important by-product from milk production and that milk and beef production is closely interlinked and therefore needs to be considered in an integrated approach. Conclusions To obtain valid LCA/CF numbers for milk, it is crucial to account for by-products. Moreover, if CF numbers for milk need to be compared, the same allocation procedure should be applied. © 2011 Springer-Verlag.
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19.
  • Flysjö, A., et al. (författare)
  • The impact of various parameters on the carbon footprint of milk production in New Zealand and Sweden
  • 2011
  • Ingår i: Agricultural Systems. - : Elsevier BV. - 1873-2267 .- 0308-521X. ; 104:6, s. 459-469
  • Tidskriftsartikel (refereegranskat)abstract
    • The carbon footprint (CF) of milk production was analysed at the farm gate for two contrasting production systems; an outdoor pasture grazing system in New Zealand (NZ) and a mainly indoor housing system with pronounced use of concentrate feed in Sweden (SE). The method used is based on the conceptual framework of lifecycle assessment (LCA), but only for greenhouse gas (GHG) emissions. National average data were used to model the dairy system in each country. Collection of inventory data and calculations of emissions were harmonised to the greatest extent possible for the two systems. The calculated CF for 1kg of energy corrected milk (ECM), including related by-products (surplus calves and culled cows), was 1.00kg carbon dioxide equivalents (CO2e) for NZ and 1.16kg CO2e for SE. Methane from enteric fermentation and nitrous oxide emissions from application of nitrogen (as fertiliser and as excreta dropped directly on the field) were the main contributors to the CF in both countries. The most important parameters to consider when calculating the GHG emissions were dry matter intake (DMI), emission factor (EF) for methane from enteric fermentation, amount of nitrogen applied and EF for direct nitrous oxide emissions from soils. By changing one parameter at a time within 'reasonable' limits (i.e. no extreme values assumed), the impact on the total CF was assessed and showed changes of up to 15%. In addition, the uncertainty in CF estimates due to uncertainty in EF for methane from enteric fermentation and nitrous oxide emissions (from soil and due to ammonia volatilisation) were analysed through Monte Carlo simulation. This resulted in an uncertainty distribution corresponding to 0.60-1.52kg CO2e kg-1 ECM for NZ and 0.83-1.56kg CO2e kg-1 ECM for SE (in the prediction interval 2.5-97.5%). Hence, the variation within the systems based on the main EF is relatively large compared with the difference in CF between the countries. © 2011 Elsevier Ltd.
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20.
  • Flysjö, A., et al. (författare)
  • The interaction between milk and beef production and emissions from land use change - Critical considerations in life cycle assessment and carbon footprint studies of milk
  • 2012
  • Ingår i: Journal of Cleaner Production. - : Elsevier BV. - 0959-6526 .- 1879-1786. ; 28, s. 134-142
  • Tidskriftsartikel (refereegranskat)abstract
    • Two most critical factors to address in environmental system analysis of future milk production are 1) the link between milk and beef production, and 2) the competition for land, possibly leading to land use change (LUC) with greenhouse gas (GHG) emissions and loss of biodiversity as important implications. Different methodological approaches concerning these factors, in studies on environmental impacts of dairy production, sometimes lead to contradictory results. Increasing milk yield per cow is often one of the solutions discussed in order to reduce GHG emissions from milk production. However, when also accounting for other systems affected (e.g. beef production) it is not certain that an increase in milk yield per cow leads to a reduction in total GHG emissions per kg milk. In the present study the correlation between carbon footprint (CF) of milk and the amount of milk delivered per cow is investigated for 23 dairy farms (both organic and conventional) in Sweden. Use of a fixed allocation factor of 90% (based on economic value) indicates a reduction in CF with increased milk yield, while no correlation can be noted when system expansion is applied. The average CF for two groups of farms, organic and high yielding conventional, is also calculated. When conducting system expansion the CF is somewhat lower for the organic farms (which have a lower milk yield per cow, but more meat per kg milk), but when a 90% allocation factor is used, the CF is somewhat higher for the organic farms compared to the high yielding conventional farms. In analysis of future strategies for milk production, it is suggested that system expansion should be applied, in order to also account for environmental impacts from affected systems. Thus, scenarios for milk and meat production should be analysed in an integrated approach in order to reduce total emissions from the livestock sector. How to account for emissions from LUC is highly debated and there is no current shared consensus. Different LUC methods result in significantly different results. In this study, four different LUC methods are applied, using data for organic milk production and high yielding conventional milk production systems in Sweden. Depending on which LUC method was applied, the organic system showed about 50% higher or 40% lower CF compared to the conventional high yielding system. Thus, when reporting CF numbers, it is important to report LUC-factors separately and clearly explain the underlying assumptions, since the method of accounting for LUC can drastically change the results. © 2011 Elsevier Ltd. All rights reserved.
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21.
  • Fransson, Maria, et al. (författare)
  • Early Coagulopathy in Patients With Ruptured Abdominal Aortic Aneurysm
  • 2012
  • Ingår i: Clinical and applied thrombosis/hemostasis. - : SAGE Publications. - 1076-0296 .- 1938-2723. ; 18:1, s. 96-99
  • Tidskriftsartikel (refereegranskat)abstract
    • Ruptured abdominal aortic aneurysm (AAA) is associated with a high mortality despite surgical management. Earlier reports indicate that a major cause of immediate intraoperative death in patients with ruptured AAA is related to hemorrhage due to coagulopathy. Acidosis is, besides hypothermia and hemodilution, a possible cause of coagulopathy. The aim of the present study was to investigate the incidence of coagulopathy and acidosis preoperatively in patients with ruptured AAA in relation to the clinical outcome with special regard to the influence of shock. For this purpose, 95 consecutive patients who underwent surgery for AAA (43 ruptured with shock, 12 ruptured without shock, and 40 nonruptured) were included. Coagulopathy was defined as prothrombin time (international normalized ratio [INR]) >= 1.5 and acidosis was defined as base deficit >= 6 mmol/L. Mortality and postoperative complications were recorded. The present study shows a state of acidosis at the start of surgery in 30 of 55 patients with ruptured AAA. However, only in 7 of 55 patients with ruptured AAA a state of preoperative coagulopathy was demonstrated. Furthermore, in our patients with shock due to ruptured AAA only 2 of 12 deaths were due to coagulopathy and bleeding. Indeed, our results show a relatively high incidence of thrombosis-related causes of death in patients with ruptured AAA, indicating a relation to an activated coagulation in these patients. These findings indicate that modern emergency management of ruptured AAA has improved in the attempt to prevent fatal coagulopathy.
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22.
  • Gad, Helge, et al. (författare)
  • MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
  • 2014
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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23.
  • Gardin, Emily, et al. (författare)
  • Consonant inventory of Swedish speaking 24-month-olds : A cross-sectional study
  • 2014
  • Ingår i: Proceedings from FONETIK 2014. - Stockholm : Department of Linguistics, Stockholm University. - 9789163756627 - 9789163756634 ; , s. 123-126
  • Konferensbidrag (refereegranskat)abstract
    • This cross-sectional study examines the consonant inventory of Swedish speaking twenty-four-month olds. The results are compared with English speaking children at the same age. 15 audio files recorded from 13 children were transcribed using independent analysis. Individual inventories where constructed for both word-initial and word-final consonants for each subject. The results are to a high degree consistent with the findings in the study compared. Anterior consonants are more frequent in the subject’s inventories than posterior ones in both initial and final word position. Word initial voiced plosives are more common in the inventories than voiceless with the reverse situation i.e. voiceless plosives are more frequent than voiced in word final position.
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24.
  • Gustafsson, Sofia B, et al. (författare)
  • High tumour cannabinoid CB(1) receptor immunoreactivity negatively impacts disease-specific survival in stage II microsatellite stable colorectal cancer
  • 2011
  • Ingår i: PLOS ONE. - San Francisco, CA : Public Library of Science. - 1932-6203. ; 6:8, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is good evidence in the literature that the cannabinoid system is disturbed in colorectal cancer. In the present study, we have investigated whether CB(1) receptor immunoreactive intensity (CB(1)IR intensity) is associated with disease severity and outcome. Methodology/Principal Findings: CB(1)IR was assessed in formalin-fixed, paraffin-embedded specimens collected with a consecutive intent during primary tumour surgical resection from a series of cases diagnosed with colorectal cancer. Tumour centre (n = 483) and invasive front (n = 486) CB(1)IR was scored from 0 (absent) to 3 (intense staining) and the data was analysed as a median split i.e. CB(1)IR <2 and >= 2. In microsatellite stable, but not microsatellite instable tumours (as adjudged on the basis of immunohistochemical determination of four mismatch repair proteins), there was a significant positive association of the tumour grade with the CB1IR intensity. The difference between the microsatellite stable and instable tumours for this association of CB(1)IR was related to the CpG island methylation status of the cases. Cox proportional hazards regression analyses indicated a significant contribution of CB(1)IR to disease-specific survival in the microsatellite stable tumours when adjusting for tumour stage. For the cases with stage II microsatellite stable tumours, there was a significant effect of both tumour centre and front CB(1)IR upon disease specific survival. The 5 year probabilities of event-free survival were: 8565 and 66+/-8%; tumour interior, 86+/-4% and 63+/-8% for the CB(1)IR<2 and CB(1)IR >= 2 groups, respectively. Conclusions/Significance: The level of CB(1) receptor expression in colorectal cancer is associated with the tumour grade in a manner dependent upon the degree of CpG hypermethylation. A high CB(1)IR is indicative of a poorer prognosis in stage II microsatellite stable tumour patients.
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25.
  • Henriksson, Aron, et al. (författare)
  • Diagnosis Code Assignment Support Using Random Indexing of Patient Records : A Qualitative Feasibility Study
  • 2011
  • Ingår i: Artificial Intelligence in Medicine. - : Springer Verlag.
  • Konferensbidrag (refereegranskat)abstract
    • The prediction of diagnosis codes is typically based on free-text entries in clinical documents. Previous attempts to tackle this problem range from strictly rule-based systems to utilizing various classification algorithms, resulting in varying degrees of success. A novel approach is to build a word space model based on a corpus of coded patient records, associating co-occurrences of words and ICD-10 codes. Random Indexing is a computationally efficient implementation of the word space model and may prove an effective means of providing support for the assignment of diagnosis codes. The method is here qualitatively evaluated for its feasibility by a physician on clinical records from two Swedish clinics. The assigned codes were in this initial experiment found among the top 10 generated suggestions in 20% of the cases, but a partial match in 77% demonstrates the potential of the method.
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26.
  • Henriksson, Aron, et al. (författare)
  • Exploration of Adverse Drug Reactions in Semantic Vector Space Models of Clinical Text
  • 2012
  • Ingår i:
  • Konferensbidrag (refereegranskat)abstract
    • A novel method for identifying potential side-effects to medications through large-scale analysis of clinical data is here introduced and evaluated. By calculating distributional similarities for medication-symptom pairs based on co-occurrence information in a large clinical corpus, many known adverse drug reactions are successfully identified. These preliminary results suggest that semantic vector space models of clinical text could also be used to generate hypotheses about potentially unknown adverse drug reactions. In the best model, 50% of the terms in a list of twenty are considered to be conceivable side-effects. Among the medication-symptom pairs, however, diagnostic indications and terms related to the medication in other ways also appear. These relations need to be distinguished in a more refined method for detecting adverse drug reactions.
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27.
  • Henriksson, Aron, et al. (författare)
  • Synonym extraction and abbreviation expansion with ensembles of semantic spaces
  • 2014
  • Ingår i: Journal of Biomedical Semantics. - : Springer Science and Business Media LLC. - 2041-1480. ; 5:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Terminologies that account for variation in language use by linking synonyms and abbreviations to their corresponding concept are important enablers of high-quality information extraction from medical texts. Due to the use of specialized sub-languages in the medical domain, manual construction of semantic resources that accurately reflect language use is both costly and challenging, often resulting in low coverage. Although models of distributional semantics applied to large corpora provide a potential means of supporting development of such resources, their ability to isolate synonymy from other semantic relations is limited. Their application in the clinical domain has also only recently begun to be explored. Combining distributional models and applying them to different types of corpora may lead to enhanced performance on the tasks of automatically extracting synonyms and abbreviation-expansion pairs. Results: A combination of two distributional models – Random Indexing and Random Permutation – employed in conjunction with a single corpus outperforms using either of the models in isolation. Furthermore, combining semantic spaces induced from different types of corpora – a corpus of clinical text and a corpus of medical journal articles – further improves results, outperforming a combination of semantic spaces induced from a single source, as well as a single semantic space induced from the conjoint corpus. A combination strategy that simply sums the cosine similarity scores of candidate terms is generally the most profitable out of the ones explored. Finally, applying simple post-processing filtering rules yields substantial performance gains on the tasks of extracting abbreviation-expansion pairs, but not synonyms. The best results, measured as recall in a list of ten candidate terms, for the three tasks are: 0.39 for abbreviations to long forms, 0.33 for long forms to abbreviations, and 0.47 for synonyms. Conclusions: This study demonstrates that ensembles of semantic spaces can yield improved performance on the tasks of automatically extracting synonyms and abbreviation-expansion pairs. This notion, which merits further exploration, allows different distributional models – with different model parameters – and different types of corpora to be combined, potentially allowing enhanced performance to be obtained on a wide range of natural language processing tasks.
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28.
  • Henriksson, Aron, et al. (författare)
  • Synonym Extraction of Medical Terms from Clinical Text Using Combinations of Word Space Models
  • 2012
  • Ingår i: Proceedings of the 5th International Symposium on Semantic Mining in Biomedicine (SMBM 2012). - 9783033038233 ; 2012, s. 10-17
  • Konferensbidrag (refereegranskat)abstract
    • In information extraction, it is useful to know if two signifiers have the same or very similar semantic content. Maintaining such information in a controlled vocabulary is, however, costly. Here it is demonstrated how synonyms of medical terms can be extracted automatically from a large corpus of clinical text using distributional semantics. By combining Random Indexing and Random Permutation, different lexical semantic aspects are captured, effectively increasing our ability to identify synonymic relations between terms. 44% of 340 synonym pairs from MeSH are successfully extracted in a list of ten suggestions. The models can also be used to map abbreviations to their full-length forms; simple pattern-based filtering of the suggestions yields substantial improvements.
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29.
  • Henriksson, Greger, 1963-, et al. (författare)
  • Environmental Policy Instruments Seen as Negotiations
  • 2012
  • Ingår i: Negotiating Environmental Conflicts. - Frankfurt am Main : Institut für Kulturanthropologie und Europäische Ethnologie. - 0724-4169. - 9783923992836 ; , s. 83-105-
  • Bokkapitel (refereegranskat)
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30.
  • Henriksson, Greger, 1963-, et al. (författare)
  • Hållbar avfallshantering : utvärdering av styrmedel från ett psykologiskt och etnologiskt perspektiv
  • 2011
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Inom psykologi och etnologi studeras företeelser ur perspektiv som återfinns hos den enskilda individen samt i det lokala eller sociala sammanhanget. I studien har olika styrmedel bedömts från ett etnologiskt och psykologiskt perspektiv. Studien har därvid inneburit nya arbetsmetoder – i varken psykologi eller etnologi brukar man arbeta med att förutsäga hur olika medel (t.ex. styrmedel) påverkar människan, normalt arbetar man efter att beskriva hur människan upplever ett befintligt styrmedel. Nytt i arbetssättet är också att utvärdera styrmedlen i olika framtidsscenarier. De viktigaste slutsatserna om de studerade styrmedlen är enligt följande. Information är ett viktigt styrmedel, men bör främst ses i kombination med andra styrmedel. Information bör utformas så att den är anpassad för olika grupper, hellre än massutskick och glättiga kampanjer. Informationen bör vara både deklarativ (ge information om effekter och konsekvenser) och procedurell (beskriva hur man ska göra). Information är viktigast som styrmedel i de hållbara scenarierna, men är av betydelse i samtliga scenarier. Vad gäller verksamheter kan man skilja på information till företagsledningen och information till anställda. Styrmedlet ”Reklam ja tack” förväntas leda till minskad mängd pappersavfall och är lätt att förstå för hushållen. Styrmedlet är mest effektivt i de hållbara scenarierna. Styrmedlet bedöms verksamt även i scenariot regional marknad eftersom det då är större tryck på verksamheterna att föra ut sitt budskap. Negativ kemikaliemärkning bedöms vara ett effektivt styrmedel, och framför allt effektivare än positiv märkning. Negativ kemikaliemärkning bedöms också vara effektivt i alla scenarier. I styrmedlet viktbaserad avfallstaxa kan storleken på den rörliga delen av avfallstaxan påverka styrmedlets genomslagskraft. Viktbaserad avfallstaxa bedöms fungera bäst i de marknadsdrivna scenarierna där individen tar ett stort ansvar själv. I de hållbara scenarierna kan styrmedlet komma att upplevas negativ eftersom ansvaret för miljöfrågorna är mer överflyttade till staten från medborgarna. Miljödifferentierad avfallstaxa bedöms ge ytterst små styreffekter eftersom det med den givna utformningen kan vara svår att kommunicera med människorna. Med vissa ändringar skulle det däremot kunna bli kraftfullt. Utvecklade insamlingssystem bedöms leda till ökad källsortering i alla scenarier. Detta gäller både ökad fastighetsnära insamling och insamling i materialströmmar.
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31.
  • Henriksson, Maria, et al. (författare)
  • Carbon footprint and land requirement for dairy herd rations : Impacts of feed production practices and regional climate variations
  • 2014
  • Ingår i: Animal. - 1751-7311 .- 1751-732X. ; 8:8, s. 1329-1338
  • Tidskriftsartikel (refereegranskat)abstract
    • Feed production is a significant source of greenhouse gas (GHG) emissions from dairy production and demands large arable and pasture acreage. This study analysed how regional conditions influence GHG emissions of dairy feed rations in a life cycle perspective, that is the carbon footprint (CF) and the land area required. Factors assessed included regional climate variations, grass/clover silage nutrient quality, feedstuff availability, crop yield and feed losses. Using the Nordic feed evaluation model NorFor, rations were optimised for different phases of lactation, dry and growing periods for older cows, first calvers and heifers by regional feed advisors and combined to annual herd rations. Feed production data at farm level were based on national statistics and studies. CF estimates followed standards for life cycle assessment and used emissions factors provided by IPCC. The functional unit was 'feed consumption to produce 1 kg energy corrected milk (ECM) from a cow with annual milk yield of 9 900 kg ECM including replacement animals and feed losses'. Feed ration CF varied from 417 to 531 g CO2 e/kg ECM. Grass/clover silage contributed more than 50% of total GHG emissions. Use of higher quality silage increased ration CF by up to 5% as a result of an additional cut and increased rates of synthetic N-fertiliser. Domestically produced horse bean (Vicia faba), by-products from the sugar industry and maize silage were included in the rations with the lowest CF, but horse bean significantly increased ration land requirement. Rations required between 1.4 to 2 m2 cropland and 0.1 to 0.2 m2/kg semi-natural grassland per kg ECM and year. Higher yield levels reduced ration total CF. Inclusion of GHG emissions from land use change associated with Brazilian soya feed significantly increased ration CF. Ration CF and land use depended on ration composition, which was highly influenced by the regional availability and production of feedstuffs. The impact of individual feedstuffs on ration CF varies due to, for example, cultivation practices and climate conditions and feedstuffs should therefore be assessed in a ration and regional perspective before being used to decrease milk CF. Land use efficiency should be considered together with ration CF, as these can generate goal conflicts.
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32.
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33.
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34.
  • Henriksson, Maria (författare)
  • Greenhouse gas emissions from Swedish milk production : towards climate-smart milk production
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Greenhouse gas (GHG) emissions from food production represent 19-29% of global anthropogenic GHG and the dairy sector alone is estimated to contribute around 3%. This thesis assessed GHG estimates for milk production (i.e. milk carbon footprint (CF)) in a life cycle perspective. Uncertainties in milk CF were examined for two contrasting milk production systems (an intensive system in Sweden (SE) and a more extensive system in New Zealand (NZ)) and variations in milk CF estimates between Swedish dairy farms were determined. GHG emissions from feed production and enteric fermentation, representing around 85% of milk CF, were estimated on herd level for different feeding strategies related to regional conditions for feed cultivation. The methodology used was Life Cycle Assessment with the system boundary 'cradle to farm gate'. National average milk CF for SE and NZ was estimated to be 1.16 and 1.00 kg carbon dioxide equivalents (CO₂e)/kg energy corrected milk (ECM) respectively, with uncertainty of approximately ±30% due to uncertainties in emissions factors predicting enteric CH₄ and soil N₂O emissions, which were among the most influential parameters for milk CF estimates. The most influential variable was feed intake. Milk CF was found to vary by approximately ±17% between Swedish dairy farms due to differences in management practices, indicating potential for reducing GHG emissions on farm level. GHG emissions from different feeding strategies varied between 0.42 and 0.53 kg CO₂e/kg ECM for feed production, and between 0.50 and 0.52 kg CO₂e/kg ECM for corresponding enteric CH₄. Thus differences in feeding strategy affected GHG emissions from feed production more than enteric CH₄ production. Roughage production contributed >50% of the emissions and grass silage CF varied markedly (by 17%) between regions and influenced the overall emissions. It was also influenced by feed losses from silage storage and feeding. Grass silage nutrient quality also influenced emissions from feed production and enteric CH₄ production. Replacement animals contributed approximately 20% of these GHG. The large uncertainties in milk CF indicate that values should not be compared unless estimated with harmonised methods and that caution is needed when they are used in mitigation studies. Efficient use of all resources is an important general mitigation measure. Measures with varying effects need to be evaluated at farm level.
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35.
  • Henriksson, Maria, et al. (författare)
  • Impact of cultivation strategies and regional climate on greenhouse gas emissions from grass/clover silage
  • 2012
  • Ingår i: Acta agriculturae Scandinavica. Section A, Animal science. - : Informa UK Limited. - 0906-4702 .- 1651-1972. ; 62:4, s. 233-237
  • Tidskriftsartikel (refereegranskat)abstract
    • More than half the annual dry matter intake (DMI) of feed by dairy cows can be roughage. Its production and storage constitute a significant part of the life cycle greenhouse gas (GHG) emissions from milk production. This study estimated and analysed the impact of grass/clover silage production practices in five climatically different dairy production regions in Sweden on emitted GHG. GHG emissions calculated by the life cycle assessment method were 0.46-0.54 and 0.48-0.63 kg carbon dioxide equivalents per kg silage DMI for normal and higher silage nutrient quality, respectively. Crop cultivation for higher nutrient quality through an extra cut and increased nitrogen fertilisation rates increased GHG emissions by up to 16%. Varying the yield level by +/-20% decreased (11%)/increased (15%) GHG emissions per kg DMI. Improved management practices can reduce GHG emissions feed production, but accurate estimates of yield levels and feed losses are needed to reduce uncertainties.
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36.
  • Henriksson, Maria L, et al. (författare)
  • Colorectal Cancer Cells Activate Adjacent Fibroblasts Resulting in FGF1/FGFR3 Signaling and Increased Invasion.
  • 2011
  • Ingår i: American Journal of Pathology. - : Elsevier. - 0002-9440 .- 1525-2191. ; 178:3, s. 1387-1394
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer-associated fibroblasts expressing fibroblast activation protein (FAP) have been implicated in the invasive behavior of colorectal cancer. In this study, we use FAP expression as a marker of fibroblast activation and analyze the effect of activated fibroblasts on colorectal cancer migration and invasion in experimental cell studies. We also investigated the expression pattern of FAP in cancer-associated fibroblasts during transformation from benign to malignant colorectal tumors. In immunohistochemical analyses, FAP was expressed in fibroblasts in all colorectal cancer samples examined, whereas all normal colon, hyperplastic polyps, or adenoma samples were negative. In in vitro studies, conditioned medium from colon cancer cells, but not adenoma cells, activated fibroblasts by inducing FAP expression. These activated fibroblasts increased the migration and invasion of colon cancer cells in Boyden chamber experiments and in a three-dimensional cell culture model. We identify fibroblast growth factor 1/fibroblast growth factor receptor 3 (FGF1/FGFR-3) signaling as mediators leading to the increased migration and invasion. Activated fibroblasts increase their expression of FGF1, and by adding a fibroblast growth factor receptor inhibitor, as well as an FGF1-neutralizing antibody, we reduced the migration of colon cancer cells. Our findings provide evidence of a possible molecular mechanism involved in the cross talk between cancer cells and fibroblasts leading to cancer cell invasion.
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37.
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38.
  • Henriksson, Maria P., et al. (författare)
  • What is Coded into Memory in the Absence of Outcome Feedback?
  • 2010
  • Ingår i: Journal of Experimental Psychology. Learning, Memory and Cognition. - : American Psychological Association (APA). - 0278-7393 .- 1939-1285. ; 36:1, s. 1-16
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Although people often have to learn from environments with scarce and highly selective outcome feedback, the question of how non-feedback trials are represented in memory and affect later performance has received little attention in models of learning and decision making. In this article, the Generalized Context Model (R. M. Nosofsky, 1986) is used as a vehicle to test contrasting hypotheses about the coding of non-feedback trials. Data across 3 experiments with selective decision-contingent and selective outcome-contingent feedback provide support for the hypothesis of constructivist coding (E. Elwin, P. Juslin, H. Olsson, & T. Enkvist, 2007), according to which the outcomes on non-feedback trials are coded with the most likely outcome, as inferred by the individual. The relation to sampling-based approaches to judgment, and the adaptive significance of constructivist coding, are discussed.
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39.
  • Henriksson, Maria, et al. (författare)
  • Variation in carbon footprint of milk due to management differences between Swedish dairy farms
  • 2011
  • Ingår i: Animal. - 1751-7311 .- 1751-732X. ; 5:9, s. 1474-1484
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify mitigation options to reduce greenhouse gas (GHG) emissions from milk production (i.e. the carbon footprint (CF) of milk), this study examined the variation in GHG emissions among dairy farms using data from previous CF studies on Swedish milk. Variations between farms in these production data, which were found to have a strong influence on milk CF, were obtained from existing databases of 1051 dairy farms in Sweden in 2005. Monte Carlo (MC) analysis was used to analyse the impact of variations in seven important parameters on milk CF concerning milk yield (energy-corrected milk (ECM) produced and delivered), feed dry matter intake (DMI), enteric CH4 emissions, N content in feed DMI, N-fertiliser rate and diesel used on farm. The largest between-farm variations among the analysed production data were N-fertiliser rate (kg/ha) and diesel used (l/ha) on farm (CV = 31% to 38%). For the parameters concerning milk yield and feed DMI, the CV was approximately 11% and 8%, respectively. The smallest variation in production data was found for N content in feed DMI. According to the MC analysis, these variations in production data led to a variation in milk CF of between 0.94 and 1.33 kg CO2 equivalents (CO2e)/kg ECM, with an average value of 1.13 kg CO2e/kg ECM. We consider that this variation of ±17%, which was found to be based on the used farm data, would be even greater if all Swedish dairy farms were included, as the sample of farms in this study was not totally unbiased. The variation identified in milk CF indicates that a potential exists to reduce GHG emissions from milk production on both the national and farm levels through changes in management. As milk yield and feed DMI are two of the most influential parameters for milk CF, feed conversion efficiency (i.e. units ECM produced/unit DMI) can be used as a rough key performance indicator for predicting CF reductions. However, it must be borne in mind that feeds have different CF due to where and how they are produced. © 2011 The Animal Consortium.
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40.
  • Isaksson-Mettävainio, Martin, et al. (författare)
  • High SMAD4 levels appear in MSI and hypermethylated colon cancers, and indicate a better prognosis
  • 2012
  • Ingår i: International Journal of Cancer. - Geneve : International union against cancer. - 0020-7136 .- 1097-0215. ; 131, s. 779-788
  • Tidskriftsartikel (refereegranskat)abstract
    • Colorectal cancer (CRC) is one of the most common causes of cancer related deaths in western countries. CRC are commonly divided in cancers showing microsatellite stability (MSS) or microsatellite instability (MSI). A more novel classification is dependent on promoter hypermethylation of CpG islands (the CpG island methylator phenotype, CIMP), where cancers show high, low or negative methylation status. SMAD4, located on chromosome 18q, has been thoroughly investigated during the last years. Loss of SMAD4 expression has been reported to correlate with poor CRC patient prognosis. In this study we analyze the impact of SMAD4 expression on prognosis in relation to MSI screening status and CIMP status. 479 paraffin-embedded specimens of CRC were examined for nuclear SMAD4 expression using immunohistochemistry. The tumors were scored loss (-), moderate (+) and high (++) expressing tumors. Loss of SMAD4 correlated significantly with decreased survival in all colon cancer patients. High SMAD4 expression, on the other hand, was significantly associated with increased survival, especially in colon cancer patients which has undergone potential curative surgery. In addition, in MSI tumors and CIMP-high tumors, high SMAD4 expression was significantly related to increase in survival, while loss of SMAD4 resulted in a significantly poorer prognosis. SMAD4 expression was not correlated to prognosis in rectal cancer cases. We conclude, loss of SMAD4 indicates a poor prognosis in colon cancer patients. The novel findings that high SMAD4 expression predicts a better prognosis suggests that SMAD4 immunohistochemistry could constitute a prognostic marker in combination with CIMP and MSI screening status.
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41.
  • Kitahara, Cari M., et al. (författare)
  • Association between adult height, genetic susceptibility and risk of glioma
  • 2012
  • Ingår i: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 41:4, s. 1075-1085
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Some, but not all, observational studies have suggested that taller stature is associated with a significant increased risk of glioma. In a pooled analysis of observational studies, we investigated the strength and consistency of this association, overall and for major sub- types, and investigated effect modification by genetic susceptibility to the disease. Methods We standardized and combined individual-level data on 1354 cases and 4734 control subjects from 13 prospective and 2 case-control studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for glioma and glioma sub-types were estimated using logistic regression models stratified by sex and adjusted for birth cohort and study. Pooled ORs were additionally estimated after stratifying the models according to seven recently identified glioma-related genetic variants. Results Among men, we found a positive association between height and glioma risk (epsilon 190 vs 170-174 cm, pooled OR = 1.70, 95% CI: 1.11-2.61; P-trend = 0.01), which was slightly stronger after restricting to cases with glioblastoma (pooled OR = 1.99, 95% CI: 1.17-3.38; P-trend = 0.02). Among women, these associations were less clear (epsilon 175 vs 160-164 cm, pooled OR for glioma = 1.06, 95% CI: 0.70-1.62; P-trend = 0.22; pooled OR for glioblastoma = 1.36, 95% CI: 0.77-2.39; P-trend = 0.04). In general, we did not observe evidence of effect modification by glioma-related genotypes on the association between height and glioma risk. Conclusion An association of taller adult stature with glioma, particularly for men and stronger for glioblastoma, should be investigated further to clarify the role of environmental and genetic determinants of height in the etiology of this disease.
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42.
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43.
  • Ljuslinder, Ingrid, et al. (författare)
  • Increased epidermal growth factor receptor expression at the invasive margin is a negative prognostic factor in colorectal cancer
  • 2011
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 128:9, s. 2031-2037
  • Tidskriftsartikel (refereegranskat)abstract
    • The receptor tyrosine kinase epidermal growth factor receptor (EGFR) is often expressed in solid malignant tumours, and the expression has been correlated to disease progression. Multiple new agents targeted against the EGFR have been developed during the last decade, but treatment selecting criteria are still not clear. This immunohistochemical study includes 386 colorectal cancer patients and focuses on EGFR expression variations within the tumour, comparing central parts to the invasive margin. Positive immunostaining for EGFR was evident in the central part in 176/386 (46%) of analyzed primary tumours. The invasive margin was positive in 222/386 (58%). A similar expression in both the central part and the invasive front was evident in 286/386 (74%). An increased score at the invasive margin compared to central parts (EGFR(i)) was evident in 97/386 (25%) of the tumours. Moreover, the results show a significant survival disadvantage for the EGFR(i) group, both in potentially curatively resected colon cancer patients (n = 170, p = 0.01) and in potentially curatively resected colon and rectal cancer patients combined (n = 273, p = 0.013). Multivariate survival analysis adjusted for age, gender, bowel localisation, grade, stage and tumour type showed an increased risk of cancer death for EGFR(i) tumours (HR, 1.53; 95% CI, 1.04-2.23; p = 0.029). A significant correlation between EGFR expression at the invasive margin and the presence of budding was seen (p = 0.0001). This investigation of a large patient material implies that EGFR immunohistochemical analysis still has a role in risk evaluation of colorectal cancer patients.
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44.
  • Melin, Beatrice, et al. (författare)
  • Known glioma risk loci are associated with glioma with a family history of brain tumours : a case-control gene association study
  • 2013
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:10, s. 2464-2468
  • Tidskriftsartikel (refereegranskat)abstract
    • Familial cancer can be used to leverage genetic association studies. Recent genome-wide association studies have reported independent associations between seven single nucleotide polymorphisms (SNPs) and risk of glioma. The aim of this study was to investigate whether glioma cases with a positive family history of brain tumours, defined as having at least one first- or second-degree relative with a history of brain tumour, are associated with known glioma risk loci. One thousand four hundred and thirty-one glioma cases and 2,868 cancer-free controls were identified from four casecontrol studies and two prospective cohorts from USA, Sweden and Denmark and genotyped for seven SNPs previously reported to be associated with glioma risk in casecontrol designed studies. Odds ratios were calculated by unconditional logistic regression. In analyses including glioma cases with a family history of brain tumours (n = 104) and control subjects free of glioma at baseline, three of seven SNPs were associated with glioma risk: rs2736100 (5p15.33, TERT), rs4977756 (9p21.3, CDKN2A-CDKN2B) and rs6010620 (20q13.33, RTEL1). After Bonferroni correction for multiple comparisons, only one marker was statistically significantly associated with glioma risk, rs6010620 (ORtrend for the minor (A) allele, 0.39; 95% CI: 0.250.61; Bonferroni adjusted ptrend, 1.7 x 104). In conclusion, as previously shown for glioma regardless of family history of brain tumours, rs6010620 (RTEL1) was associated with an increased risk of glioma when restricting to cases with family history of brain tumours. These findings require confirmation in further studies with a larger number of glioma cases with a family history of brain tumours.
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45.
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46.
  • Rajaraman, Preetha, et al. (författare)
  • Genome-wide association study of glioma and meta-analysis
  • 2012
  • Ingår i: Human Genetics. - : SPRINGER. - 0340-6717 .- 1432-1203. ; 131:12, s. 1877-1888
  • Tidskriftsartikel (refereegranskat)abstract
    • Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.
  •  
47.
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48.
  • Skeppstedt, Maria, et al. (författare)
  • Vocabulary Expansion by Semantic Extraction of Medical Terms
  • 2013
  • Ingår i: Proceedings of the 5th International Symposiumon Languages in Biology and Medicine. - 9784990780203 ; , s. 63-68
  • Konferensbidrag (refereegranskat)abstract
    • Automatic methods for vocabulary expansion are valuable in supporting the development of terminological resources. Here, we evaluate two methods based on distributional semantics for extracting terms that belong to a certain semantic category. In a list of 1000 terms extracted from a corpus of Swedish medical text, the best method obtains a recall of 0.53 and 0.88, respectively, for identifying 90 terms that are known to belong to the semantic categories Medical Finding and Pharmaceutical Drug.
  •  
49.
  • Stacey, Simon N, et al. (författare)
  • Ancestry-shift refinement mapping of the C6orf97-ESR1 breast cancer susceptibility locus.
  • 2010
  • Ingår i: PLoS genetics. - : Public Library of Science. - 1553-7404. ; 6:7, s. e1001029-
  • Tidskriftsartikel (refereegranskat)abstract
    • We used an approach that we term ancestry-shift refinement mapping to investigate an association, originally discovered in a GWAS of a Chinese population, between rs2046210[T] and breast cancer susceptibility. The locus is on 6q25.1 in proximity to the C6orf97 and estrogen receptor alpha (ESR1) genes. We identified a panel of SNPs that are correlated with rs2046210 in Chinese, but not necessarily so in other ancestral populations, and genotyped them in breast cancer case:control samples of Asian, European, and African origin, a total of 10,176 cases and 13,286 controls. We found that rs2046210[T] does not confer substantial risk of breast cancer in Europeans and Africans (OR = 1.04, P = 0.099, and OR = 0.98, P = 0.77, respectively). Rather, in those ancestries, an association signal arises from a group of less common SNPs typified by rs9397435. The rs9397435[G] allele was found to confer risk of breast cancer in European (OR = 1.15, P = 1.2 x 10(-3)), African (OR = 1.35, P = 0.014), and Asian (OR = 1.23, P = 2.9 x 10(-4)) population samples. Combined over all ancestries, the OR was 1.19 (P = 3.9 x 10(-7)), was without significant heterogeneity between ancestries (P(het) = 0.36) and the SNP fully accounted for the association signal in each ancestry. Haplotypes bearing rs9397435[G] are well tagged by rs2046210[T] only in Asians. The rs9397435[G] allele showed associations with both estrogen receptor positive and estrogen receptor negative breast cancer. Using early-draft data from the 1,000 Genomes project, we found that the risk allele of a novel SNP (rs77275268), which is closely correlated with rs9397435, disrupts a partially methylated CpG sequence within a known CTCF binding site. These studies demonstrate that shifting the analysis among ancestral populations can provide valuable resolution in association mapping.
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