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1.	Destouni, Georgia, et al. (författare) Hydro-Biogeochemical and Environmental-Management Functions of Wetland Networks in Landscapes 2012 Ingår i: 9th INTECOL International Wetlands Conference, Wetlands in a Complex World. ; , s. 915- Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract A main application goal of ecohydrological science is to amplify opportunities of achieving water quality improvements, biodiversity enhancements and sustainable development, by improved understanding and use of ecosystem properties as a management tool. This paper draws on and synthesizes main result implications for the function and possible enhanced use of wetland networks in the landscape as such a tool, from a series of hydro-biogeochemical and environmental economics studies of nutrient/pollutant loading and abatement in different Swedish hydrological catchments. Results show large potential of wetland networks to reduce the cost of abating nutrient and metal loads within and from hydrological catchments, and emphasize some main research questions for further investigations of actual possibilities to realize this potential. The questions regard in particular the ability of wetland networks to extend the travel times and reduce the uncertainty of hydrological nutrient/pollutant transport through catchments.The paper further presents and discusses some main joint conclusions of the participants in a recently held International Workshop on Ecohydrology and Integrated Water Resource Management (1) at the Navarino Environmental Observatory in Messinia, Greece (2), regarding essential goals for collaborative international efforts in wetland network research. The goals include to investigate on different spatiotemporal scales and in different world regions: a) the dynamics of natural and managed wetland networks across a gradient of different climate, human disturbance, energy and organization conditions; b) the reciprocal interactions between wetland networks and associated hydrological catchments; c) how climate change and different human activities in the wetland network catchments influence these interactions (in b) and generally the ecohydrology of individual wetlands and the whole wetland networks; and d) the ecosystem services provided by networks of wetlands.
2.	Giesler, Reiner, et al. (författare) Catchment-scale dissolved carbon concentrations and exportestimates across six subarctic streams in northern Sweden 2014 Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 11:2, s. 525-537 Tidskriftsartikel (refereegranskat)abstract Climatic change is currently enhancing permafrost thawing and the flow of water through the landscape in subarctic and arctic catchments, with major consequences for the carbon export to aquatic ecosystems. We studied stream water carbon export in several tundra-dominated catchments in northern Sweden. There were clear seasonal differences in both dissolved organic carbon (DOC) and dissolved inorganic carbon (DIC) concentrations. The highest DOC concentrations occurred during the spring freshet while the highest DIC concentrations were always observed during winter baseflow conditions for the six catchments considered in this study. Long-term trends for the period 1982 to 2010 for one of the streams showed that DIC concentrations has increased by 9% during the 28 yr of measurement while no clear trend was found for DOC. Similar increasing trends were also found for conductivity, Ca and Mg. When trends were discretized into individual months, we found a significant linear increase in DIC concentrations with time for September, November and December. In these subarctic catchments, the annual mass of C exported as DIC was in the same order of magnitude as DOC; the average proportion of DIC to the total dissolved C exported was 61% for the six streams. Furthermore, there was a direct relationship between total runoff and annual dissolved carbon fluxes for these six catchments. These relationships were more prevalent for annual DIC exports than annual DOC exports in this region. Our results also highlight that both DOC and DIC can be important in high-latitude ecosystems. This is particularly relevant in environments where thawing permafrost and changes to subsurface ice due to global warming can influence stream water fluxes of C. The large proportion of stream water DIC flux also has implications on regional C budgets and needs to be considered in order to understand climate-induced feedback mechanisms across the landscape.
3.	Helou, Khalil, 1966, et al. (författare) Comparative genome hybridization reveals specific genomic imbalances during the genesis from benign through borderline to malignant ovarian tumors. 2006 Ingår i: Cancer genetics and cytogenetics. - : Elsevier BV. - 0165-4608. ; 170:1, s. 1-8 Tidskriftsartikel (refereegranskat)abstract Ovarian cancer is one of the most common types of malignancy in women throughout the developed world. Despite recent therapeutic advances, long-term survival is poor because ovarian cancer is largely asymptomatic in its early stages. Comparative genomic hybridization (CGH) was applied to a series of 8 benign, 8 borderline, and 17 malignant ovarian to establish genomic imbalances associated with tumor progression. Benign and borderline tumors were characterized by losses at 1p32 approximately p11, 2q14 approximately q34, 4q13 approximately q34, 5q11 approximately q23, and 6q12 approximately q24, as well as gains of 6p and chromosome 12. Similar chromosomal changes were also detected in malignant tumors but included additional chromosomal changes: gains at 1q21 approximately q31, 2p, 3q, 5p, 7, 10p, 12p, 16p, 17, 19q, 20q, and 22q, as well as losses at X, 3p, 8p, 9, 11p, 13, 14, and 18. Some individual cases of benign and borderline tumors revealed no genetic alterations detectable by CGH, suggesting that these tumors may represent a subset of tumors that originate by an alternative mechanism of tumorigenesis. Furthermore, our findings reveal that borderline tumors are more similar to benign tumors than to malignant tumors with respect to their genetic profiles.
4.	Karlsson, Elin, 1979, et al. (författare) Chromosomal changes associated with clinical outcome in lymph node-negative breast cancer. 2007 Ingår i: Cancer genetics and cytogenetics. - : Elsevier BV. - 0165-4608 .- 1873-4456. ; 172:2, s. 139-46 Tidskriftsartikel (refereegranskat)abstract Breast cancer is the most common malignancy among women and accounts for over one million new cases worldwide per year. Lymph node-negative breast cancer patients are reputed as having a better prognosis than lymph node-positive ones. Around 20% of the lymph node-negative patients die within 10 years after diagnosis. To improve the prognostics of node-negative breast cancer, it is important to understand the underlying biologic mechanisms promoting survival, such as specific genetic changes in the tumor genome. In this study, CGH was applied to analyze 64 tumors from node-negative breast cancer patients to identify DNA copy number changes in chromosomes and chromosome regions that may be correlated to survival. The main findings show gains at 4q, 5q31 approximately qter, 6q12 approximately q16, and 12q14 approximately q22, as well as losses of 17p, 18p, and Xq, which were significantly more recurrent in tumors from deceased patients than in tumors from survivors. The average number of chromosomal changes was higher in the tumors from deceased compared to the survivor tumors. Our findings suggest that tumors with specific chromosomal aberrations at 4q, 5q31 approximately qter, 6q12 approximately q16, 12q14 approximately q22, 17p, 18p, and Xq result in an aggressive form of breast cancer and that these patients are predisposed to succumb to breast cancer.
5.	Karlsson, Elin, 1979, et al. (författare) Gene expression variation to predict 10-year survival in lymph-node-negative breast cancer. 2008 Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 8 Tidskriftsartikel (refereegranskat)abstract It is of great significance to find better markers to correctly distinguish between high-risk and low-risk breast cancer patients since the majority of breast cancer cases are at present being overtreated.
6.	Moberg, Christina, et al. (författare) De unga gör helt rätt när de stämmer staten 2022 Ingår i: Aftonbladet. - 1103-9000. Tidskriftsartikel (populärvet., debatt m.m.)abstract 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
7.	Ran, Ylva, et al. (författare) Environmental assessment of diets: overview and guidance on indicator choice 2024 Ingår i: The Lancet Planetary Health. - : Elsevier BV. - 2542-5196. ; 8:3, s. e172-e187 Forskningsöversikt (refereegranskat)abstract Comprehensive but interpretable assessment of the environmental performance of diets involves choosing a set of appropriate indicators. Current knowledge and data gaps on the origin of dietary foodstuffs restrict use of indicators relying on site-specific information. This Personal View summarises commonly used indicators for assessing the environmental performance of diets, briefly outlines their benefits and drawbacks, and provides recommendations on indicator choices for actors across multiple fields involved in activities that include the environmental assessment of diets. We then provide recommendations on indicator choices for actors across multiple fields involved in activities that use environmental assessments, such as health and nutrition experts, policy makers, decision makers, and private-sector and public-sector sustainability officers. We recommend that environmental assessment of diets should include indicators for at least the five following areas: climate change, biosphere integrity, blue water consumption, novel entities, and impacts on natural resources (especially wild fish stocks), to capture important environmental trade-offs. If more indicators can be handled in the assessment, indicators to capture impacts related to land use quantity and quality and green water consumption should be used. For ambitious assessments, indicators related to biogeochemical flows, stratospheric ozone depletion, and energy use can be added.
8.	Ran, Ylva, et al. (författare) Environmental assessment of diets: overview and guidance on indicator choice 2024 Ingår i: The Lancet Planetary Health. - : ELSEVIER SCI LTD. - 2542-5196. ; 8:3, s. e172-e187 Forskningsöversikt (refereegranskat)abstract Comprehensive but interpretable assessment of the environmental performance of diets involves choosing a set of appropriate indicators. Current knowledge and data gaps on the origin of dietary foodstuffs restrict use of indicators relying on site-specific information. This Personal View summarises commonly used indicators for assessing the environmental performance of diets, briefly outlines their benefits and drawbacks, and provides recommendations on indicator choices for actors across multiple fields involved in activities that include the environmental assessment of diets. We then provide recommendations on indicator choices for actors across multiple fields involved in activities that use environmental assessments, such as health and nutrition experts, policy makers, decision makers, and private-sector and public-sector sustainability officers. We recommend that environmental assessment of diets should include indicators for at least the five following areas: climate change, biosphere integrity, blue water consumption, novel entities, and impacts on natural resources (especially wild fish stocks), to capture important environmental trade-offs. If more indicators can be handled in the assessment, indicators to capture impacts related to land use quantity and quality and green water consumption should be used. For ambitious assessments, indicators related to biogeochemical flows, stratospheric ozone depletion, and energy use can be added.
9.	Ran, Ylva, et al. (författare) Environmental assessment of diets: overview and guidance on indicator choice 2024 Ingår i: The Lancet Planetary Health. - 2542-5196. ; 8:3, s. e172-e187 Tidskriftsartikel (refereegranskat)abstract Comprehensive but interpretable assessment of the environmental performance of diets involves choosing a set of appropriate indicators. Current knowledge and data gaps on the origin of dietary foodstuffs restrict use of indicators relying on site-specific information.This Personal View summarises commonly used indicators for assessing the environmental performance of diets, briefly outlines their benefits and drawbacks, and provides recommendations on indicator choices for actors across multiple fields involved in activities that include the environmental assessment of diets.We then provide recommendations on indicator choices for actors across multiple fields involved in activities that use environmental assessments, such as health and nutrition experts, policy makers, decision makers, and private-sector and public-sector sustainability officers. We recommend that environmental assessment of diets should include indicators for at least the five following areas: climate change, biosphere integrity, blue water consumption, novel entities, and impacts on natural resources (especially wild fish stocks), to capture important environmental trade-offs.If more indicators can be handled in the assessment, indicators to capture impacts related to land use quantity and quality and green water consumption should be used. For ambitious assessments, indicators related to biogeochemical flows, stratospheric ozone depletion, and energy use can be added.
10.	Ran, Ylva, et al. (författare) Environmental assessment of diets: overview and guidance on indicator choice 2024 Ingår i: The Lancet Planetary Health. - : ELSEVIER SCI LTD. - 2542-5196. ; 8:3, s. e172-e187 Tidskriftsartikel (refereegranskat)abstract Comprehensive but interpretable assessment of the environmental performance of diets involves choosing a set of appropriate indicators. Current knowledge and data gaps on the origin of dietary foodstuffs restrict use of indicators relying on site-specific information. This Personal View summarises commonly used indicators for assessing the environmental performance of diets, briefly outlines their benefits and drawbacks, and provides recommendations on indicator choices for actors across multiple fields involved in activities that include the environmental assessment of diets. We then provide recommendations on indicator choices for actors across multiple fields involved in activities that use environmental assessments, such as health and nutrition experts, policy makers, decision makers, and privatesector and public-sector sustainability officers. We recommend that environmental assessment of diets should include indicators for at least the five following areas: climate change, biosphere integrity, blue water consump tion, novel entities, and impacts on natural resources (especially wild fish stocks), to capture important environ mental trade-offs. If more indicators can be handled in the assessment, indicators to capture impacts related to land use quantity and quality and green water consumption should be used. For ambitious assessments, indicators related to biogeochemical flows, stratospheric ozone depletion, and energy use can be added.
11.	Aevarsson, Arnthór, et al. (författare) Going to extremes - a metagenomic journey into the dark matter of life 2021 Ingår i: FEMS Microbiology Letters. - : Oxford University Press (OUP). - 1574-6968. ; 368:12 Forskningsöversikt (refereegranskat)abstract The Virus-X-Viral Metagenomics for Innovation Value-project was a scientific expedition to explore and exploit uncharted territory of genetic diversity in extreme natural environments such as geothermal hot springs and deep-sea ocean ecosystems. Specifically, the project was set to analyse and exploit viral metagenomes with the ultimate goal of developing new gene products with high innovation value for applications in biotechnology, pharmaceutical, medical, and the life science sectors. Viral gene pool analysis is also essential to obtain fundamental insight into ecosystem dynamics and to investigate how viruses influence the evolution of microbes and multicellular organisms. The Virus-X Consortium, established in 2016, included experts from eight European countries. The unique approach based on high throughput bioinformatics technologies combined with structural and functional studies resulted in the development of a biodiscovery pipeline of significant capacity and scale. The activities within the Virus-X consortium cover the entire range from bioprospecting and methods development in bioinformatics to protein production and characterisation, with the final goal of translating our results into new products for the bioeconomy. The significant impact the consortium made in all of these areas was possible due to the successful cooperation between expert teams that worked together to solve a complex scientific problem using state-of-the-art technologies as well as developing novel tools to explore the virosphere, widely considered as the last great frontier of life.
12.	Agrenius, Stefan, 1948, et al. (författare) Marine Invertebrates 2005 Ingår i: The 2005 Red List of Swedish Species. - Uppsala : Artdatabanken, SLU. - 9188506304 ; , s. 409-447 Bokkapitel (övrigt vetenskapligt/konstnärligt)
13.	Aguilar, Helena, et al. (författare) VAV3 mediates resistance to breast cancer endocrine therapy 2014 Ingår i: Breast Cancer Research. - : BioMed Central. - 1465-5411 .- 1465-542X. ; 16:3, s. R53- Tidskriftsartikel (refereegranskat)abstract INTRODUCTION: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor alpha (ERalpha) are among the most effective systemic treatments for ERalpha-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through mechanisms that involve ERalpha transcriptional regulatory plasticity. Here, we identify VAV3 as a critical component in this process.METHODS: A cell-based chemical compound screen was carried out to identify therapeutic strategies against resistance to endocrine therapy. Binding to ERalpha was evaluated by molecular docking analyses, an agonist fluoligand assay, and short-hairpin (sh) RNA-mediated protein depletion. Microarray analyses were performed to identify altered gene expression. Western blot of signaling and proliferation markers and shRNA-mediated protein depletion in viability and clonogenic assays were performed to delineate the role of VAV3. Genetic variation in VAV3 was assessed for association with the response to tamoxifen. Immunohistochemical analyses of VAV3 were carried out to determine the association with therapy response and different tumor markers. An analysis of gene expression association with drug sensitivity was carried out to identify a potential therapeutic approach based on differential VAV3 expression.RESULTS: The compound YC-1 was found to comparatively reduce the viability of cell models of acquired resistance. This effect was probably not due to activation of its canonical target (soluble guanylyl cyclase) but instead a result of binding to ERalpha. VAV3 was selectively reduced upon exposure to YC-1 or ERalpha depletion and, accordingly, VAV3 depletion comparatively reduced the viability of cell models of acquired resistance. In the clinical scenario, germline variation in VAV3 was associated with response to tamoxifen in Japanese breast cancer patients (rs10494071 combined P value = 8.4 x 10-4). The allele association combined with gene expression analyses indicated that low VAV3 expression predicts better clinical outcome. Conversely, high nuclear VAV3 expression in tumor cells was associated with poorer endocrine therapy response. Based on VAV3 expression levels and the response to erlotinib in cancer cell lines, targeting EGFR signaling may be a promising therapeutic strategy.CONCLUSIONS: This study proposes VAV3 as a biomarker and rationale signaling target to prevent and/or overcome resistance to endocrine therapy in breast cancer.
14.	Ahnström Waltersson, Marie, 1976-, et al. (författare) miR-206 expression is downregulated in cyclin D1 amplified breast tumours Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Amplification in the 11q13 region has been found in around 15% of all breast cancers and is strongly correlated with oestrogen receptor (ER) positive tumours. We have previously found that amplification of at least one of the genes PAK1 or CCND1 is associated with decreased recurrencefree survival among ER+ patients. Other genes in the amplicon might also contribute to this effect and situated close to CCND1 are the FGF-3, -4 and - 19 genes. The FGF-4 protein has been shown to inhibit the expression of the ERα regulator miR-206 in chicken embryo. In this study we analysed 23 tumours with and 27 tumours without previously detected 11q13 amplification to explore if 11q13 amplification is associated with decreased levels of miR-206 and if miR-206 is associated with ER expression. Using real-time PCR, we found that miR-206 expression was inversely correlated to CCND1 and 11q13 amplification (P=0.016 and P=0.022 respectively). Tumours with low miR-206 expression had higher levels of ERα than tumours with intermediate and high expression (P=0.043). We conclude that miR-206 might be an important regulator of the ERα. Our finding that low mir-206 is associated with CCND1 amplification and thereby also FGF-4 amplification points towards the possibility of a miR-206 regulator, FGF-4 or another FGF, present in the amplicon.
15.	Alexopoulou, Sofia, 1984- (författare) "Please Mind the Grey Digital Divide" : An Analysis of Digital Public Policies in Light of the Welfare State (Sweden and Greece) 2022 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract This thesis examines the grey digital divide and digital policies in the divergent welfare regimes of Sweden and Greece. The grey digital divide is a serious problem not only for the individual but also for society. The grey digital divide signifies the inability of older people to utilize digital technology. In academic circles, the emphasis is mostly on the technological aspects of the grey digital divide or on the individual characteristics of older people as (non)users of digital tools. However, the problem is more complex in nature and is interconnected with the aging process and experience. The grey digital divide has multiple levels: the first concerns access, the second skills, and the third opportunities. This thesis concentrates mostly on the third level of digital divide because it touches on the welfare denominator. This particular level describes the encounters that older citizens need to have with the digital welfare state and the obstacles that they might face in doing this. Older digital “offliners” cannot take advantage of the welfare services that they need for their own well-being and cannot participate as equal citizens in digital space, which is expanding on a daily basis with new digital services.This thesis is situated in the discipline of political science and draws on various disciplines, such as political science (welfare regime theory, neo-institutionalism, and path-dependency), public policy (active aging paradigm), gerontology (disengagement), sociology (exclusion via the digital-by-default approach), and ICT studies (the phenomenon of digitalization and the third-level of the digital divide). The thesis is a compilation of papers and consists of two qualitative case studies, a comparative study, and a scoping literature review. The key findings are as follows: 1) older people are a heterogeneous group and this applies in the digital world as well, with the appearance of heterogeneous digital profiles; 2) the welfare regime seems to affect the manifestation of the grey digital divide and there is a path-dependency pattern in this; 3) the more digitalized a society, the greater the chance that older people not using technology will be excluded from the digital and social spheres; and 4) digital policies indicate the priorities of every society and how older people are perceived as a social group.
16.	Alriksson, Stina, 1971-, et al. (författare) Temporal risk assessment – 20th century Pb emissions to air and exposure via inhalation in the Swedish glass district 2023 Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 858:1 Tidskriftsartikel (refereegranskat)abstract The objective of the present study was to assess historical emissions of Pb to air around a number of glassworks sites in southeastern Sweden, and the possible implications for human exposure. To do so, a four-step method was applied. First, emissions of Pb to air around 10 glassworks were modelled for the 20th century. Second, an assessment of the resulting exposure was made for a number of scenarios. Third, the number of people potentially exposed at different times was estimated, and fourth, measurements of “current” Pb concentrations in PM10 material from four sites were conducted in 2019. The results show that the highest emissions, and exposures, occurred from 1970 to1980. It coincides with the time period when the highest number of people resided in the villages. At this time, the average Pb concentration in air around the six largest factories was about 2.4 μg Pb/m3, i.e. 16 times the present US national ambient air quality standard (NAAQS) of 0.15 μg Pb/m3. By year 2000 the modelled average concentration had dropped to 0.05 μg Pb/m3, a level that is normal for urban regions today. The PM10 measurements from 2019 indicate a further decline, now with a mean value of about 0.02 μg Pb/m3. Over the entire study period, inhalation hazard quotients (HQs) exceeded the dietary HQ by many orders of magnitude, indicating that inhalation has been the most prevalent exposure pathway in the past. At present, both pathways are judged to be associated with low exposures. Even if only roughly approximated, a picture of the historical exposure can increase our understanding of the connection between exposure and disease, and can be valuable when risks are to be communicated to residents near contaminated areas.
17.	Anand, Aseem, et al. (författare) Assessing Radiographic Response to 223Ra with an Automated Bone Scan Index in Metastatic Castration-Resistant Prostate Cancer Patients 2020 Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X .- 1535-5667. ; 61:5, s. 671-675 Tidskriftsartikel (refereegranskat)abstract For effective clinical management of patients being treated with 223Ra, there is a need for radiographic response biomarkers to minimize disease progression and to stratify patients for subsequent treatment options. The objective of this study was to evaluate an automated bone scan index (aBSI) as a quantitative assessment of bone scans for radiographic response in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: In a multicenter retrospective study, bone scans from patients with mCRPC treated with monthly injections of 223Ra were collected from 7 hospitals in Sweden. Patients with available bone scans before treatment with 223Ra and at treatment discontinuation were eligible for the study. The aBSI was generated at baseline and at treatment discontinuation. The Spearman rank correlation was used to correlate aBSI with the baseline covariates: alkaline phosphatase (ALP) and prostate-specific antigen (PSA). The Cox proportional-hazards model and Kaplan-Meier curve were used to evaluate the association of covariates at baseline and their change at treatment discontinuation with overall survival (OS). The concordance index (C-index) was used to evaluate the discriminating strength of covariates in predicting OS. Results: Bone scan images at baseline were available from 156 patients, and 67 patients had both a baseline and a treatment discontinuation bone scan (median, 5 doses; interquartile range, 3-6 doses). Baseline aBSI (median, 4.5; interquartile range, 2.4-6.5) was moderately correlated with ALP (r = 0.60, P < 0.0001) and with PSA (r = 0.38, P = 0.003). Among baseline covariates, aBSI (P = 0.01) and ALP (P = 0.001) were significantly associated with OS, whereas PSA values were not (P = 0.059). After treatment discontinuation, 36% (24/67), 80% (54/67), and 13% (9/67) of patients demonstrated a decline in aBSI, ALP, and PSA, respectively. As a continuous variable, the relative change in aBSI after treatment, compared with baseline, was significantly associated with OS (P < 0.0001), with a C-index of 0.67. Median OS in patients with both aBSI and ALP decline (median, 134 wk) was significantly longer than in patients with ALP decline only (median, 77 wk; P = 0.029). Conclusion: Both aBSI at baseline and its change at treatment discontinuation were significant parameters associated with OS. The study warrants prospective validation of aBSI as a quantitative imaging response biomarker to predict OS in patients with mCRPC treated with 223Ra.
18.	Andersson, Anna, et al. (författare) Waterworks-specific composition of drinking water disinfection by-products 2019 Ingår i: Environmental Science. - Cambridge : Royal Society of Chemistry. - 2053-1400 .- 2053-1419. ; :5, s. 861-872 Tidskriftsartikel (refereegranskat)abstract Reactions between chemical disinfectants and natural organic matter (NOM) upon drinking water treatment result in formation of potentially harmful disinfection by-products (DBPs). The diversity of DBPs formed is high and a large portion remains unknown. Previous studies have shown that non-volatile DBPs are important, as much of the total toxicity from DBPs has been related to this fraction. To further understand the composition and variation of DBPs associated with this fraction, non-target analysis with ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was employed to detect DBPs at four Swedish waterworks using different types of raw water and treatments. Samples were collected five times covering a full year. A common group of DBPs formed at all four waterworks was detected, suggesting a similar pool of DBP precursors in all raw waters that might be related to phenolic moieties. However, the largest proportion (64–92%) of the assigned chlorinated and brominated molecular formulae were unique, i.e. were solely found in one of the four waterworks. In contrast, the compositional variations of NOM in the raw waters and samples collected prior to chemical disinfection were rather limited.This indicated that waterworks-specific DBPs presumably originated from matrix effects at the point of disinfection, primarily explained by differences in bromide levels, disinfectants (chlorine versus chloramine) and different relative abundances of isomers among the NOM compositions studied. The large variation of observed DBPs in the toxicologically relevant non-volatile fraction indicates that non-targeted monitoring strategies might be valuable to ensure relevant DBP monitoring in the future.
19.	Andersson, Elin, et al. (författare) Quantification of chondroitin sulfate, hyaluronic acid and N-glycans in synovial fluid – A technical performance study 2023 Ingår i: Osteoarthritis and Cartilage Open. - 2665-9131. ; 5:3, s. 1-11 Tidskriftsartikel (refereegranskat)abstract ObjectiveTo validate a quantitative high performance liquid chromatography (HPLC) assay for chondroitin sulfate (CS) and hyaluronic acid (HA) in synovial fluid, and to analyze glycan-patterns in patient samples.DesignSynovial fluid from osteoarthritis (OA, n = 25) and knee-injury (n = 13) patients, a synovial fluid pool (SF-control) and purified aggrecan, were chondroitinase digested and together with CS- and HA-standards fluorophore labelled prior to quantitative HPLC analysis. N-glycan profiles of synovial fluid and aggrecan were assessed by mass spectrometry.ResultsUnsaturated uronic acid and sulfated-N-acetylgalactosamine (ΔUA-GalNAc4S and ΔUA-GalNAc6S) contributed to 95% of the total CS-signal in the SF-control sample. For HA and the CS variants in SF-control the intra- and inter-experiment coefficient of variation was between 3–12% and 11–19%, respectively; tenfold dilution gave recoveries between 74 and 122%, and biofluid stability test (room temperature storage and freeze-thaw cycles) showed recoveries between 81 and 140%. Synovial fluid concentrations of the CS variants ΔUA-GalNAc6S and ΔUA2S-GalNAc6S were three times higher in the recent injury group compared to the OA group, while HA was four times lower. Sixty-one different N-glycans were detected in the synovial fluid samples, but there were no differences in levels of N-glycan classes between patient groups. The CS-profile (levels of ΔUA-GalNAc4S and ΔUA-GalNAc6S) in synovial fluid resembled that of purified aggrecan from corresponding samples; the contribution to the N-glycan profile in synovial fluid from aggrecan was low.ConclusionsThe HPLC-assay is suitable for analyzing CS variants and HA in synovial fluid samples, and the GAG-pattern differs between OA and recently knee injured subjects.
20.	Andersson, Elin, et al. (författare) Quantification of chondroitin sulfate, hyaluronic acid and N-glycans in synovial fluid – A technical performance study 2023 Ingår i: Osteoarthritis and Cartilage Open. - 2665-9131. ; 5:3 Tidskriftsartikel (refereegranskat)abstract Objective: To validate a quantitative high performance liquid chromatography (HPLC) assay for chondroitin sulfate (CS) and hyaluronic acid (HA) in synovial fluid, and to analyze glycan-patterns in patient samples. Design: Synovial fluid from osteoarthritis (OA, n = 25) and knee-injury (n = 13) patients, a synovial fluid pool (SF-control) and purified aggrecan, were chondroitinase digested and together with CS- and HA-standards fluorophore labelled prior to quantitative HPLC analysis. N-glycan profiles of synovial fluid and aggrecan were assessed by mass spectrometry. Results: Unsaturated uronic acid and sulfated-N-acetylgalactosamine (ΔUA-GalNAc4S and ΔUA-GalNAc6S) contributed to 95% of the total CS-signal in the SF-control sample. For HA and the CS variants in SF-control the intra- and inter-experiment coefficient of variation was between 3–12% and 11–19%, respectively; tenfold dilution gave recoveries between 74 and 122%, and biofluid stability test (room temperature storage and freeze-thaw cycles) showed recoveries between 81 and 140%. Synovial fluid concentrations of the CS variants ΔUA-GalNAc6S and ΔUA2S-GalNAc6S were three times higher in the recent injury group compared to the OA group, while HA was four times lower. Sixty-one different N-glycans were detected in the synovial fluid samples, but there were no differences in levels of N-glycan classes between patient groups. The CS-profile (levels of ΔUA-GalNAc4S and ΔUA-GalNAc6S) in synovial fluid resembled that of purified aggrecan from corresponding samples; the contribution to the N-glycan profile in synovial fluid from aggrecan was low. Conclusions: The HPLC-assay is suitable for analyzing CS variants and HA in synovial fluid samples, and the GAG-pattern differs between OA and recently knee injured subjects.
21.	Arvidsson Segerkvist, Katarina, et al. (författare) Consumer driven innovation towards improved beef and lamb meat quality : Partnership project summary 2021 Rapport (övrigt vetenskapligt/konstnärligt)
22.	Beiron, Johanna, 1992, et al. (författare) The role of BECCS in providing negative emissions in Sweden under competing interests for forest-based biomass 2022 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Negative emissions are needed to meet climate mitigation targets and can be achieved through the capture and storage of biogenic CO2 emissions (BECCS). Sweden holds a large potential for BECCS from the industry and heat and power sectors. This work provides a first assessment of how the conditions for BECCS in Sweden are impacted by competition for forest-based biomass from other sectors, in this work represented by production of transportation fuels. An optimization model is applied to study how demand levels for negative emissions and biofuels, and availability of forestry resources, influence the optimal system design considering the electricity, district heating and biomass sectors. BECCS and direct air capture technologies are available for investments in the model. The results show that biomass availability and biofuel demand have a large impact on the choice of negative emission technology, where high competition for biomass favours DACCS rather than BECCS. The available biomass is prioritized for use in fuel production and sets the upper limit for BECCS. In this work, CHP plants are more competitive for BECCS implementation than pulp mills, due to the energy penalty for CHP plants having a smaller impact on the overall energy system performance. The findings indicate that in addition to considering techno-economic assessments of individual technologies, it is important to take into account the system context in which they operate.
23.	Berglund, Karin, et al. (författare) Oroande att docenters meriter börjat ifrågasättas 2024 Ingår i: Universitetsläraren. - 0282-4973. Tidskriftsartikel (populärvet., debatt m.m.)
24.	Bernson, Elin, 1987, et al. (författare) Identification of Tissue-Resident Natural Killer and T Lymphocytes with Anti-Tumor Properties in Ascites of Ovarian Cancer Patients 2023 Ingår i: Cancers. - 2072-6694. ; 15:13 Tidskriftsartikel (refereegranskat)abstract Simple Summary Ovarian cancer is the deadliest among gynecological cancers, and there is a huge demand for new treatments for these patients. Immunotherapy holds great potential in cancer treatment, but has not yet proven successful for the majority of ovarian cancer patients. To better understand the immunological landscape of the disease, we have characterized lymphocytes in patients with high-grade serous ovarian cancer. Natural killer cells and T cells are present in both primary tumors and in the metastasizing environment of ascites, a fluid in the abdominal cavity that is developed in many patients with ovarian cancer. Our data reveal that a large fraction of these natural killer cells and T cells express tissue-resident markers and the inhibitory receptor, NKG2A, and are able to kill ovarian cancer cells. In summary, we report a functional subset of lymphocytes that may be targeted in future immunotherapeutic approaches. Women with ovarian cancer have limited therapy options, with immunotherapy being unsatisfactory for a large group of patients. Tumor cells spread from the ovary or the fallopian tube into the abdominal cavity, which is commonly accompanied with massive ascites production. The ascites represents a unique peritoneal liquid tumor microenvironment with the presence of both tumor and immune cells, including cytotoxic lymphocytes. We characterized lymphocytes in ascites from patients with high-grade serous ovarian cancer. Our data reveal the presence of NK and CD8(+) T lymphocytes expressing CD103 and CD49a, which are markers of tissue residency. Moreover, these cells express high levels of the inhibitory NKG2A receptor, with the highest expression level detected on tissue-resident NK cells. Lymphocytes with these features were also present at the primary tumor site. Functional assays showed that tissue-resident NK cells in ascites are highly responsive towards ovarian tumor cells. Similar results were observed in an in vivo mouse model, in which tissue-resident NK and CD8(+) T cells were detected in the peritoneal fluid upon tumor growth. Together, our data reveal the presence of highly functional lymphocyte populations that may be targeted to improve immunotherapy for patients with ovarian cancer.
25.	Björk, Anne, et al. (författare) Genetic variation in the vitamin D receptor gene is not associated with measures of muscle strength, physical performance, or falls in elderly men. Data from MrOS Sweden. Annan publikation (övrigt vetenskapligt/konstnärligt)
26.	Björk, Anne, et al. (författare) Genetic variation in the vitamin D receptor gene is not associated with measures of muscle strength, physical performance, or falls in elderly men. Data from MrOS Sweden. Annan publikation (övrigt vetenskapligt/konstnärligt)
27.	Bojmar, Linda, et al. (författare) 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 Annan publikation (övrigt vetenskapligt/konstnärligt)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.
28.	Bojmar, Linda, et al. (författare) The Role of MicroRNA-200 in Progression of Human Colorectal and Breast Cancer 2013 Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:12, s. 84815- Tidskriftsartikel (refereegranskat)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.
29.	Boonstra, M. D., et al. (författare) Social Insurance Literacy of Dutch Workers Receiving Disability Benefits and its Associations with Socio-Economic Characteristics 2022 Ingår i: Journal of occupational rehabilitation. - : Springer / Plenum. - 1053-0487 .- 1573-3688. ; 32, s. 494-504 Tidskriftsartikel (refereegranskat)abstract Purpose This study explores the concept social insurance literacy (SIL) and corresponding questionnaire (SILQ) among workers receiving disability benefits and the comprehensibility of the social security institute (SSI), and examines associations with socio-economic characteristics. Methods 1753 panel members of the Dutch SSI were approached to complete the SILQ-NL37. This measure was based on the original SILQ. The SILQ-NL37 contains domains for obtaining, understanding and acting upon information for both individual SIL and system comprehensibility. A higher score means better SIL or comprehensibility. Data on age, gender, education, living situation, Dutch skills and time receiving disability benefits were also collected. With k-means clustering, groups with adequate and limited SIL were created. Associations with socio-economic characteristics were examined with independent t-tests and linear regression analyses for both the total scores and within domain scores. Cronbach alpha and Spearman rhos indicated measurement properties were good to acceptable for the SILQ-NL37. Results Thirty-five percent of the 567 participants were in the group with limited SIL. Higher individual SILQ-NL37 scores were associated with having a partner (p = 0.018) and northeastern living region (p = 0.031). Higher scores for obtaining (p = 0.041) and understanding (p = 0.049) information were associated with female sex, and for acting on information with younger age (p = 0.020). People with limited Dutch skills (p = 0.063) and a partner (p = 0.085) rated system comprehensibility higher. Conclusions According to the SILQ-NL37 scores, about 35% of the panel members have limited ability to obtain, understand and act upon social insurance systems information. Limited SIL is associated with several socio-economic factors. Future researches should study the concept in a more representative sample, and in different countries and social insurance contexts.
30.	Bostner, Josefine, et al. (författare) Activation of Akt, mTOR, and the estrogen receptor as a signature to predict tamoxifen treatment benefit 2013 Ingår i: Breast Cancer Research and Treatment. - : Springer Verlag (Germany). - 0167-6806 .- 1573-7217. ; 137:2, s. 397-406 Tidskriftsartikel (refereegranskat)abstract The frequent alterations of the PI3K/Akt/mTOR-growth signaling pathway are proposed mechanisms for resistance to endocrine therapy in breast cancer, partly through regulation of estrogen receptor alpha (ER) activity. Reliable biomarkers for treatment prediction are required for improved individualized treatment. We performed a retrospective immunohistochemical analysis of primary tumors from 912 postmenopausal patients with node-negative breast cancer, randomized to either tamoxifen or no adjuvant treatment. Phosphorylated (p) Akt-serine (s) 473, p-mTOR-s2448, and ER phosphorylations-s167 and -s305 were evaluated as potential biomarkers of prognosis and tamoxifen treatment efficacy. High expression of p-mTOR indicated a reduced response to tamoxifen, most pronounced in the ER+/progesterone receptor (PgR) + subgroup (tamoxifen vs. no tamoxifen: hazard ratio (HR), 0.86; 95 % confidence interval (CI), 0.31-2.38; P = 0.78), whereas low p-mTOR expression predicted tamoxifen benefit (HR, 0.29; 95 % CI, 0.18-0.49; P = 0.000002). In addition, nuclear p-Akt-s473 as well as p-ER at -s167 and/or -s305 showed interaction with tamoxifen efficacy with borderline statistical significance. A combination score of positive pathway markers including p-Akt, p-mTOR, and p-ER showed significant association with tamoxifen benefit (test for interaction; P = 0.029). Cross-talk between growth signaling pathways and ER-signaling has been proposed to affect tamoxifen response in hormone receptor-positive breast cancer. The results support this hypothesis, as an overactive pathway was significantly associated with reduced response to tamoxifen. A clinical pre-treatment test for cross-talk markers would be a step toward individualized adjuvant endocrine treatment with or without the addition of PI3K/Akt/mTOR pathway inhibitors.
31.	Bostner, Josefine, et al. (författare) S6 kinase signaling and tamoxifen response in breast cancer cells and in two randomized breast cancer cohorts 2013 Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Detecting signals in the mammalian target of rapamycin (mTOR), and the estrogen receptor (ER) pathways for prediction of treatment response may be a future clinical tool in primary breast cancer. Here, we investigated the validity and value of the mTOR targets p70-S6 kinase (S6K) 1 and 2 as biomarkers for tamoxifen sensitivity in vitro and in two independent tamoxifen randomized postmenopausal breast cancer cohorts. In addition, the prognostic value of the S6Ks was evaluated. A simultaneous knockdown of the S6Ks in ER-positive breast cancer cells resulted in G1 arrest, and tamoxifen-induced G1 arrest was in part S6K1+S6K2 dependent, suggesting separate roles in proliferation and in tamoxifen response. We found S6K1 to correlate with HER2 and cytoplasmic Akt activity, whereas S6K2 and phosphorylated S6K were closer connected with ER positivity, low proliferation and nucleic p-Akt. Treatment prediction and prognosis were evaluated by immunohistochemical staining. Nuclear accumulation of S6K1 was indicative of a reduced tamoxifen treatment effect, compared with a significant benefit from tamoxifen treatment in patients without tumor S6K1 nuclear accumulation. Patients with a combination of S6K1 nuclear accumulation and S6K2 cytoplasmic accumulation in the tumor cells had no tamoxifen benefit. Also, S6K1 and S6K2 activation, indicated by p-S6K-t389 expression, was associated with low benefit from tamoxifen compared with untreated patients. In addition, high protein expression of S6K1, independent of localization, predicted worse prognosis. This was not evident for variations in S6K2 or p-S6K-t389 expression.In conclusion, the mTOR targeted kinases S6K1 and S6K2 interfere with proliferation and response to tamoxifen. Monitoring their activity andintracellular localization may provide biomarkers for breast cancer treatment, allowing for identification of a group of patients less likely tobenefit from tamoxifen and thus in need of an alternative or additional treatment.
32.	Bostner, Josefine, et al. (författare) S6 kinase signaling: tamoxifen response and prognostic indication in two breast cancer cohorts 2015 Ingår i: Endocrine-Related Cancer. - : BioScientifica. - 1351-0088 .- 1479-6821. ; 22:3, s. 331-343 Tidskriftsartikel (refereegranskat)abstract Detection of signals in the mammalian target of rapamycin (mTOR) and the estrogen receptor (ER) pathways may be a future clinical tool for the prediction of adjuvant treatment response in primary breast cancer. Using immunohistological staining, we investigated the value of the mTOR targets p70-S6 kinase (S6K) 1 and 2 as biomarkers for tamoxifen benefit in two independent clinical trials comparing adjuvant tamoxifen with no tamoxifen or 5 years versus 2 years of tamoxifen treatment. In addition, the prognostic value of the S6Ks was evaluated. We found that S6K1 correlated with proliferation, HER2 status, and cytoplasmic AKT activity, whereas high protein expression levels of S6K2 and phosphorylated (p) S6K were more common in ER-positive, and low-proliferative tumors with pAKT-s473 localized to the nucelus. Nuclear accumulation of S6K1 was indicative of a reduced tamoxifen effect (hazard ratio (HR): 1.07, 95% CI: 0.53-2.81, P=0.84), compared with a significant benefit from tamoxifen treatment in patients without tumor S6K1 nuclear accumulation (HR: 0.42, 95% CI: 0.29-0.62, Pless than0.00001). Also S6K1 and S6K2 activation, indicated by pS6K-t389 expression, was associated with low benefit from tamoxifen (HR: 0.97, 95% CI: 0.50-1.87, P=0.92). In addition, high protein expression of S6K1, independent of localization, predicted worse prognosis in a multivariate analysis, P=0.00041 (cytoplasm), P=0.016 (nucleus). In conclusion, the mTOR-activated kinases S6K1 and S6K2 interfere with proliferation and response to tamoxifen. Monitoring their activity and intracellular localization may provide biomarkers for breast cancer treatment, allowing the identification of a group of patients less likely to benefit from tamoxifen and thus in need of an alternative or additional targeted treatment.
33.	Bovinder Ylitalo, Erik, et al. (författare) Excellent cabazitaxel response in prostate cancer xenografts expressing androgen receptor variant 7 and reversion of resistance development by anti-androgens Annan publikation (övrigt vetenskapligt/konstnärligt)
34.	Bovinder Ylitalo, Erik, et al. (författare) Marked response to cabazitaxel in prostate cancer xenografts expressing androgen receptor variant 7 and reversion of acquired resistance by anti-androgens 2020 Ingår i: Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 80:1, s. 214-224 Tidskriftsartikel (refereegranskat)abstract Background Taxane treatment may be a suitable therapeutic option for patients with castration-resistant prostate cancer and high expression of constitutively active androgen receptor variants (AR-Vs). The aim of the study was to compare the effects of cabazitaxel and androgen deprivation treatments in a prostate tumor xenograft model expressing high levels of constitutively active AR-V7. Furthermore, mechanisms behind acquired cabazitaxel resistance were explored. Methods Mice were subcutaneously inoculated with 22Rv1 cells and treated with surgical castration (n = 7), abiraterone (n = 9), cabazitaxel (n = 6), castration plus abiraterone (n = 8), castration plus cabazitaxel (n = 11), or vehicle and/or sham operation (n = 23). Tumor growth was followed for about 2 months or to a volume of approximately 1000 mm(3). Two cabazitaxel resistant cell lines; 22Rv1-CabR1 and 22Rv1-CabR2, were established from xenografts relapsing during cabazitaxel treatment. Differential gene expression between the cabazitaxel resistant and control 22Rv1 cells was examined by whole-genome expression array analysis followed by immunoblotting, immunohistochemistry, and functional pathway analysis. Results Abiraterone treatment alone or in combination with surgical castration had no major effect on 22Rv1 tumor growth, while cabazitaxel significantly delayed and in some cases totally abolished 22Rv1 tumor growth on its own and in combination with surgical castration. The cabazitaxel resistant cell lines; 22Rv1-CabR1 and 22Rv1-CabR2, both showed upregulation of the ATP-binding cassette sub-family B member 1 (ABCB1) efflux pump. Treatment with ABCB1 inhibitor elacridar completely restored susceptibility to cabazitaxel, while treatment with AR-antagonists bicalutamide and enzalutamide partly restored susceptibility to cabazitaxel in both cell lines. The cholesterol biosynthesis pathway was induced in the 22Rv1-CabR2 cell line, which was confirmed by reduced sensitivity to simvastatin treatment. Conclusions Cabazitaxel efficiently inhibits prostate cancer growth despite the high expression of constitutively active AR-V7. Acquired cabazitaxel resistance involving overexpression of efflux transporter ABCB1 can be reverted by bicalutamide or enzalutamide treatment, indicating the great clinical potential for combined treatment with cabazitaxel and anti-androgens.
35.	Brill, Margreke JE, et al. (författare) Confirming model-predicted pharmacokinetic interactions between bedaquiline and lopinavir/ritonavir or nevirapine in patients with HIV and drug resistant tuberculosis 2017 Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 0924-8579 .- 1872-7913. ; 49, s. 212-217 Tidskriftsartikel (refereegranskat)abstract Bedaquiline and its metabolite M2 are metabolised by CYP3A4. The antiretrovirals ritonavir-boosted lopinavir (LPV/r) and nevirapine inhibit and induce CYP3A4, respectively. Here we aimed to quantify nevirapine and LPV/r drug–drug interaction effects on bedaquiline and M2 in patients co-infected with HIV and multidrug-resistant tuberculosis (MDR-TB) using population pharmacokinetic (PK) analysis and compare these with model-based predictions from single-dose studies in subjects without TB. An observational PK study was performed in three groups of MDR-TB patients during bedaquiline maintenance dosing: HIV-seronegative patients (n = 17); and HIV-infected patients using antiretroviral therapy including nevirapine (n = 17) or LPV/r (n = 14). Bedaquiline and M2 samples were collected over 48 h post-dose. A previously developed PK model of MDR-TB patients was used as prior information to inform parameter estimation using NONMEM. The model was able to describe bedaquiline and M2 concentrations well, with estimates close to their priors and earlier model-based interaction effects from single-dose studies. Nevirapine changed bedaquiline clearance to 82% (95% CI 67–99%) and M2 clearance to 119% (92–156%) of their original values, indicating no clinically significant interaction. LPV/r substantially reduced bedaquiline clearance to 25% (17–35%) and M2 clearance to 59% (44–69%) of original values. This work confirms earlier model-based predictions of nevirapine and LPV/r interaction effects on bedaquiline and M2 clearance from subjects without TB in single-dose studies, in MDR-TB/HIV co-infected patients studied here. To normalise bedaquiline exposure in patients with concomitant LPV/r therapy, an adjusted bedaquiline dosing regimen is proposed for further study.
36.	Carlsson, Elin, et al. (författare) In vitro and in vivo response to low-modulus PMMA-based bone cement 2015 Ingår i: BioMed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141. Tidskriftsartikel (refereegranskat)abstract The high stiffness of acrylic bone cements has been hypothesized to contribute to the increased number of fractures encountered after vertebroplasty, which has led to the development of low-modulus cements. However, there is no data available on the in vivo biocompatibility of any low-modulus cement. In this study, the in vitro cytotoxicity and in vivo biocompatibility of two types of low-modulus acrylic cements, one modified with castor oil and one with linoleic acid, were evaluated using human osteoblast-like cells and a rodent model, respectively. While the in vitro cytotoxicity appeared somewhat affected by the castor oil and linoleic acid additions, no difference could be found in the in vivo response to these cements in comparison to the base, commercially available cement, in terms of histology and flow cytometry analysis of the presence of immune cells. Furthermore, the in vivo radiopacity of the cements appeared unaltered. While these results are promising, the mechanical behavior of these cements in vivo remains to be investigated.
37.	Chorell, Elin, et al. (författare) Impact of probiotic feeding during weaning on the serum lipid profile and plasma metabolome in infants 2013 Ingår i: British Journal of Nutrition. - : Cambridge University Press. - 0007-1145 .- 1475-2662. ; 110:1, s. 116-126 Tidskriftsartikel (refereegranskat)abstract The gut microbiome interacts with the host in the metabolic response to diet, and early microbial aberrancies may be linked to the development of obesity and metabolic disorders later in life. Probiotics have been proposed to affect metabolic programming and blood lipid levels, although studies are lacking in infants. Here, we report on the lipid profile and global metabolic response following daily feeding of probiotics during weaning. A total of 179 healthy, term infants were randomised to daily intake of cereals with (n 89) or without (n 90) the addition of Lactobacillus paracasei ssp. paracasei F19 (LF19) 108 colony-forming units per serving from 4 to 13 months of age. Weight, length and skinfold thickness were monitored. Venous blood was drawn at 5·5 and 13 months of age for analysis of the serum lipid profile. In a subsample, randomly selected from each group, GC-time-of-flight/MS was used to metabolically characterise plasma samples from thirty-seven infants. A combination of multi- and univariate analysis was applied to reveal differences related to LF19 treatment based on 228 putative metabolites, of which ninety-nine were identified or classified. We observed no effects of probiotic feeding on anthropometrics or the serum lipid profile. However, we detected significantly lower levels of palmitoleic acid (16 : 1) (P < 0·05) and significantly higher levels of putrescine (P < 0·01) in LF19-treated infants. Palmitoleic acid is a major MUFA strongly linked to visceral obesity, while putrescine is a polyamine with importance for gut integrity. Whether the observed differences will have long-term health consequences are being followed.
38.	Chorell, Elin, 1981-, et al. (författare) The impact of feeding Lactobacillus F19 during weaning : a study of the plasma metabolome Annan publikation (övrigt vetenskapligt/konstnärligt)
39.	Crippa, Alessio, et al. (författare) The ProBio trial : molecular biomarkers for advancing personalized treatment decision in patients with metastatic castration-resistant prostate cancer 2020 Ingår i: Trials. - : BioMed Central. - 1745-6215. ; 21:1 Tidskriftsartikel (refereegranskat)abstract Background: Multiple therapies exist for patients with metastatic castration-resistant prostate cancer (mCRPC). However, their improvement on progression-free survival (PFS) remains modest, potentially explained by tumor molecular heterogeneity. Several prognostic molecular biomarkers have been identified for mCRPC that may have predictive potential to guide treatment selection and prolong PFS. We designed a platform trial to test this hypothesis.Methods: The Prostate-Biomarker (ProBio) study is a multi-center, outcome-adaptive, multi-arm, biomarker-driven platform trial for tailoring treatment decisions for men with mCRPC. Treatment decisions in the experimental arms are based on biomarker signatures defined as mutations in certain genes/pathways suggested in the scientific literature to be important for treatment response in mCRPC. The biomarker signatures are determined by targeted sequencing of circulating tumor and germline DNA using a panel specifically designed for mCRPC.Discussion: Patients are stratified based on the sequencing results and randomized to either current clinical practice (control), where the treating physician decides treatment, or to molecularly driven treatment selection based on the biomarker profile. Outcome-adaptive randomization is implemented to early identify promising treatments for a biomarker signature. Biomarker signature-treatment combinations graduate from the platform when they demonstrate 85% probability of improving PFS compared to the control arm. Graduated combinations are further evaluated in a seamless confirmatory trial with fixed randomization. The platform design allows for new drugs and biomarkers to be introduced in the study.Conclusions: The ProBio design allows promising treatment-biomarker combinations to quickly graduate from the platform and be confirmed for rapid implementation in clinical care.
40.	Denk, Thomas, 1971-, et al. (författare) Medborgarnas inställning till automatiserat beslutsfattande 2020 Ingår i: Digitala är vi allihopa?. - Göteborg : SOM-institutet, Göteborgs universitet. - 9789189673489 ; , s. 78-89 Bokkapitel (populärvet., debatt m.m.)abstract Alltfler myndigheter inför automatiserat beslutsfattande, vilket innebär att en dator fattar beslut istället för handläggare och utredare. Detta kapitel undersöker med- borgarnas inställning till att öka det automatiserade beslutsfattandet i myndigheter. Kapitlets analyser visar att en majoritet (64 procent) anser att det är ett mycket dåligt eller ganska dåligt förslag att datorer ska få ta över fler beslut i myndigheter. Analyserna indikerar också att inställningen har samband med socio-demografisk bakgrund, politiska förhållningssätt och framtidsoro för AI, automatisering och robotisering. Den negativa inställningen återfinns i samtliga grupper. Det är dessutom så att det snarare är graden av negativ inställning som varierar mellan grupper än inställningen som sådan. Med dessa resultat framträder en möjlig spänning mellan utvecklingen inom myndigheter och medborgarnas inställning till automatiserat beslutsfattande.
41.	Denk, Thomas, et al. (författare) Medborgarnas inställning till automatiserat beslutsfattande 2020 Ingår i: Digitala är vi allihopa?. - Göteborg : SOM-institutet, Göteborgs universitet. - 9789189673489 ; , s. 79-89 Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract Alltfler myndigheter inför automatiserat beslutsfattande, vilket innebär att en dator fattar beslut istället för handläggare och utredare. Detta kapitel undersöker medborgarnas inställning till att öka det automatiserade beslutsfattandet i myndigheter. Kapitlets analyser visar att en majoritet (64 procent) anser att det är ett mycket dåligt eller ganska dåligt förslag att datorer ska få ta över flera beslut i myndigheter. Analyserna indikerar också att inställningen har samband med socio-demografisk bakgrund, politiska förhållningssätt och framtidsoro för AI, automatisering och robotisering. Den negativa inställningen återfinns i samtliga grupper. Det är dessutom så att det snarare är graden av negativ inställning som varierar mellan grupper än inställningen som sådan. Med dessa resultat framträder en möjlig spänning mellan utvecklingen inom myndigheter och medborgarnas inställning till automatiserat beslutsfattande.
42.	Dwibedi, Chinmay Kumar, et al. (författare) Long-range dispersal moved Francisella tularensis into Western Europe from the East 2016 Ingår i: Microbial Genomics. - : Microbiology Society. - 2057-5858. ; 2:12 Tidskriftsartikel (refereegranskat)abstract For many infections transmitting to humans from reservoirs in nature, disease dispersal patterns over space and time are largely unknown. Here, a reversed genomics approach helped us understand disease dispersal and yielded insight into evolution and biological properties of Francisella tularensis, the bacterium causing tularemia. We whole-genome sequenced 67 strains and characterized by single-nucleotide polymorphism assays 138 strains, collected from individuals infected 1947-2012 across Western Europe. We used the data for phylogenetic, population genetic and geographical network analyses. All strains (n= 205) belonged to a monophyletic population of recent ancestry not found outside Western Europe. Most strains (n= 195) throughout the study area were assigned to a star-like phylogenetic pattern indicating that colonization of Western Europe occurred via clonal expansion. In the East of the study area, strains were more diverse, consistent with a founder population spreading from east to west. The relationship of genetic and geographic distance within the F. tularensis population was complex and indicated multiple long-distance dispersal events. Mutation rate estimates based on year of isolation indicated null rates; in outbreak hotspots only, there was a rate of 0.4 mutations/genome/year. Patterns of nucleotide substitution showed marked AT mutational bias suggestive of genetic drift. These results demonstrate that tularemia has moved from east to west in Europe and that F. tularensis has a biology characterized by long-range geographical dispersal events and mostly slow, but variable, replication rates. The results indicate that mutation-driven evolution, a resting survival phase, genetic drift and long-distance geographical dispersal events have interacted to generate genetic diversity within this species.
43.	Einarsdottir, Berglind Osk, 1979, et al. (författare) A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma 2018 Ingår i: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9:8 Tidskriftsartikel (refereegranskat)abstract Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine.
44.	Eneroth, Hanna, et al. (författare) Environmental impact of coffee, tea and cocoa – data collection for a consumer guide for plant-based foods 2022 Rapport (övrigt vetenskapligt/konstnärligt)abstract In 2020, WWF launched a consumer guide on plant-based products targeting Swedish consumers. The development of the guide is described in a journal paper (Karlsson Potter & Röös, 2021) and the environmental impact of different plant based foods was published in a report (Karlsson Potter, Lundmark, & Röös, 2020). This report was prepared for WWF Sweden to provide scientific background information for complementing the consumer guide with information on coffee, tea and cocoa. This report includes quantitative estimations for several environmental categories (climate, land use, biodiversity and water use) of coffee (per L), tea (per L) and cocoa powder (per kg), building on the previously established methodology for the consumer guide. In addition, scenarios of consumption of coffee, tea and cocoa drink with milk/plant-based drinks and waste at household level, are presented. Tea, coffee and cacao beans have a lot in common. They are tropical perennial crops traditionally grown in the shade among other species, i.e. in agroforestry systems. Today, the production in intensive monocultures has negative impact on biodiversity. Re-introducing agroforestry practices may be part of the solution to improve biodiversity in these landscapes. Climate change will likely, due to changes in temperature, extreme weather events and increases in pests and disease, alter the areas where these crops can be grown in the future. A relatively high ratio of the global land used for coffee, tea and cocoa is certified according to sustainability standards, compared to other crops. Although research on the implications of voluntary standards on different outcomes is inconclusive, the literature supports that certifications have a role in incentivizing more sustainable farming. Coffee, tea and cocoa all contain caffeine and have a high content of bioactive compounds such as antioxidants, and they have all been associated with positive health outcomes. While there is a strong coffee culture in Sweden and coffee contributes substantially to the environmental impact of our diet, tea is a less consumed beverage. Cocoa powder is consumed as a beverage, but substantial amounts of our cocoa consumption is in the form of chocolate. Roasted ground coffee on the Swedish market had a climate impact of 4.0 kg CO2e per kg powder, while the climate impact of instant coffee powder was 11.5 kg CO2e per kg. Per litre, including the energy use for making the coffee, the total climate impact was estimated to 0.25 kg CO2e per L brewed coffee and 0.16 kg CO2e per L for instant coffee. Less green coffee beans are needed to produce the same amount of ready to drink coffee from instant coffee than from brewed coffee. Tea had a climate impact of approximately 6.3 kg CO2 e per kg dry leaves corresponding to an impact of 0.064 CO2e per L ready to drink tea. In the assessment of climate impact per cup, tea had the lowest impact with 0.013 kg CO2e, followed by black instant coffee (0.024 kg CO2e), black coffee (0.038 kg CO2e), and cocoa drink made with milk (0.33 kg CO2e). The climate impact of 1kg cocoa powder on the Swedish market was estimated to 2.8 kg CO2e. Adding milk to coffee or tea increases the climate impact substantially. The literature describes a high proportion of the total climate impact of coffee from the consumer stage due to the electricity used by the coffee machine. However, with the Nordic low-carbon energy mix, the brewing and heating of water and milk contributes to only a minor part of the climate impact of coffee. As in previous research, coffee also had a higher land use, water use and biodiversity impact than tea per L beverage. Another factor of interest at the consumer stage is the waste of prepared coffee. Waste of prepared coffee contributes to climate impact through the additional production costs and electricity for preparation, even though the latter was small in our calculations. The waste of coffee and tea at Summary household level is extensive and measures to reduce the amount of wasted coffee and tea could reduce the environmental impact of Swedish hot drink consumption. For the final evaluation of coffee and tea for the consumer guide, the boundary for the fruit and vegetable group was used. The functional unit for coffee and tea was 1 L prepared beverage without any added milk or sweetener. In the guide, the final evaluation of conventionally grown coffee is that it is ‘yellow’ (‘Consume sometimes’), and for organic produce, ‘light green’ (‘Please consume). The evaluation of conventionally grown tea is that it is ‘light green’, and for organic produce, ‘dark green’ (‘Preferably consume this’). For cocoa, the functional unit is 1 kg of cocoa powder and the boundary was taken from the protein group. The final evaluation of conventionally grown cocoa is that it is ‘orange’ (‘Be careful’), and for organically produced cocoa, ‘light green’.
45.	Engqvist, Hanna, 1985, et al. (författare) Analysis of genetic abnormalities involved in the development of ovarian tumors 2016 Ingår i: 4th Swedish Cancer Research Meeting. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
46.	Engqvist, Hanna, 1985, et al. (författare) Transcriptomic and genomic profiling of early-stage ovarian carcinomas associated with histotype and overall survival 2018 Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:80, s. 35162-35180 Tidskriftsartikel (refereegranskat)
47.	Eriksson, Anna-Lena, 1971, et al. (författare) The COMT val158met polymorphism is associated with prevalent fractures in Swedish men. 2008 Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 42:1, s. 107-12 Tidskriftsartikel (refereegranskat)abstract INTRODUCTION: Sex steroids are important for growth and maintenance of the skeleton. Catechol-O-methyltransferase (COMT) is an estrogen degrading enzyme. The COMT val158met polymorphism results in a 60-75% difference in enzyme activity between the val (high activity=H) and met (low activity=L) variants. We have previously reported that this polymorphism is associated with bone mineral density (BMD) in young men. The aim of this study was to investigate associations between COMT val158met, BMD and fractures in elderly men. METHODS: Population-based study of Swedish men 75.4, SD 3.2, years of age. Fractures were reported using standardized questionnaires. Fracture and genotype data were available from 2,822 individuals. RESULTS: Total number of individuals with self-reported fracture was 989 (35.0%). Prevalence of >or=1 fracture was 37.2% in COMT(LL), 35.7% in COMT(HL) and 30.4% in COMT(HH) (p<0.05). Early fractures (50 years of age). The OR for fracture of the non-weight bearing skeleton in COMT(HH) compared with COMT(LL+HL) was 0.74 (95% CI 0.59-0.92). No associations between COMT val158met and BMD were found in this cohort of elderly men. CONCLUSIONS: The COMT val158met polymorphism is associated with life time fracture prevalence in elderly Swedish men. This association is mainly driven by early fractures (
48.	Eriksson, Elin, et al. (författare) Carbon footprint of cartons in Europe - Carbon Footprint methodology and biogenic carbon sequestration 2010 Rapport (övrigt vetenskapligt/konstnärligt)abstract A methodology for carbon sequestration in forests used for carton production has been developed and applied. The average Carbon Footprint of converted cartons sold in Europe has been calculated and summarised. A methodology for a EU27 scenario based assessment of end of life treatment has been developed and applied. The average Carbon Footprint represents the total Greenhouse Gas emissions from one average tonne of virgin based fibres and recycled fibres produced, converted and printed in Europe.
49.	Estrada, Karol, et al. (författare) Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. 2012 Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501 Tidskriftsartikel (refereegranskat)abstract Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
50.	Forsberg, Elin, et al. (författare) Treatment with Anti-HER2 Chimeric Antigen Receptor Tumor-Infiltrating Lymphocytes (CAR-TILs) Is Safe and Associated with Antitumor Efficacy in Mice and Companion Dogs 2023 Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 15:3 Tidskriftsartikel (refereegranskat)abstract Simple Summary CAR-T cells are immune cells equipped with a claw that enable them to bind cancer cells. Usually, CAR-T cells are made using immune cells from blood. Here, we tested the hypothesis that also immune cells that reside in the tumor, so called tumor-infiltrating lymphocytes, can also be modified to carry the claw. This may mean that these cells, called CAR-TILs, will be able to attack cancer cells in two ways, using the claw or binding using its normal protein on the cell surface, the so-called T cell receptor. We show that CAR-TILs can be generated, and that they can kill melanoma cells in cell culture and in mice. Finally, to prepare for clinical trials, we also assess if CAR-TILs can be safe in a human cancer patient-like model, a companion dog suffering from cancer. Our data suggest that CAR-TILs may be a way to treat patients with melanoma but human clinical trials are needed. Patients with metastatic melanoma have a historically poor prognosis, but recent advances in treatment options, including targeted therapy and immunotherapy, have drastically improved the outcomes for some of these patients. However, not all patients respond to available treatments, and around 50% of patients with metastatic cutaneous melanoma and almost all patients with metastases of uveal melanoma die of their disease. Thus, there is a need for novel treatment strategies for patients with melanoma that do not benefit from the available therapies. Chimeric antigen receptor-expressing T (CAR-T) cells are largely unexplored in melanoma. Traditionally, CAR-T cells have been produced by transducing blood-derived T cells with a virus expressing CAR. However, tumor-infiltrating lymphocytes (TILs) can also be engineered to express CAR, and such CAR-TILs could be dual-targeting. To this end, tumor samples and autologous TILs from metastasized human uveal and cutaneous melanoma were expanded in vitro and transduced with a lentiviral vector encoding an anti-HER2 CAR construct. When infused into patient-derived xenograft (PDX) mouse models carrying autologous tumors, CAR-TILs were able to eradicate melanoma, even in the absence of antigen presentation by HLA. To advance this concept to the clinic and assess its safety in an immune-competent and human-patient-like setting, we treated four companion dogs with autologous anti-HER2 CAR-TILs. We found that these cells were tolerable and showed signs of anti-tumor activity. Taken together, CAR-TIL therapy is a promising avenue for broadening the tumor-targeting capacity of TILs in patients with checkpoint immunotherapy-resistant melanoma.

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