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1.	Abolfathi, Bela, et al. (författare) The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment 2018 Ingår i: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2 Tidskriftsartikel (refereegranskat)abstract The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
2.	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.
3.	Ahlgren, Karin, et al. (författare) De stora restaureringarna : Från Uppsala domkyrka till Skokloster 2004 Rapport (populärvet., debatt m.m.)abstract De stora restaureringarna har varit årets tema. Genom att dokumentera och analysera teori och praktik i några av 1800- och 1900-talets största restaureringar - från genomgripande stilrestaureringar till ett mer återhållsamt och tekniskt skonsamt synsätt. Därmed får vi också ett bättre underlag även för dagens ställningstagande.Föremål för våra studier är Uppsala domkyrka, Gripsholms slott, Vreta klosterkyrka, Gustav 11I:s paviljong i Haga, Kungapalatset i Vadstena och Skoklosters slott. Vi hoppas att denna utställning skall bidra till en kritisk hållning och en ökad kunskap om restaureringskonsten, som kvalificerad yrkesuppgift, tidsspegel för historiesyn och som gestaltningsideal.
4.	Amiri Rigi, Sheida, et al. (författare) (Un)Weaving (Un)Sustainability 2021 Ingår i: Proceedings of the 9th Nordic Design Research Conference : Matters of Scale - Matters of Scale. - 1604-9705. ; :9, s. 160-169, s. 161-169 Konferensbidrag (refereegranskat)abstract The spatio-temporal scale of design for sustainability has come full circle. What started within a technology-oriented global outlook, later evolving into a people-oriented and local view on change, now urges for a holistic, broad extent and multilevel design for sustainability. This paper enquires into the theories of social change that govern different approaches within the field, and positions the adhesion of socio-technical system innovation and transition design to classical modern theory, against an emergent design paradigm anchored in practice theory. By drawing on the literature of the field and comparing various models, a conceptual framework is suggested where "practice" serves as an alternative scale. In broadening the scope of analysis in design, this frame of thought can solve the inherent incompatibility of geographical, jurisdictional and institutional hierarchies as vessels to conceptualize the complex and dynamic processes through which social change is (can be) brought about.
5.	Andersson, Kristina Stefanovic, et al. (författare) Vikten av mat i hemtjänsten 2008 Rapport (övrigt vetenskapligt/konstnärligt)abstract BACKGROUND: The importance of food and meals, including the problem with malnutrition, has been discussed by caregivers, the government, the home care recipients themselves as well as their next of kin. There is a need for improvement which demands changes. AIM: To investigate the knowledge and attitudes to food and nutrition, focussing on malnutrition among the personnel in the home care services and home help inspectors, before and after education. To investigate food and nutrition, including the attitude towards it, among elderly in ordinary housing with assisted meal service and/or meal distribution, before and after education among the personnel. *To test nutrition routines among elderly in ordinary housing with assisted meal service and/or meal distribution. MATERIAL AND METHODS: The project was performed in four home care service groups in Malmö. Fifty-nine persons of the personnel participated in education at four occasions for three hour each. Of these, 52 persons answered questions regarding diet and nutrition at the first measuring and 45 persons answered questions at the seconds measuring. Sixty-three elderly home care recipients were interviewed regarding food and nutrition, of these 48 were also interviewed at the end of the project. RESULTS: The questionnaire showed that the knowledge of food and nutrition among the personnel was satisfying already before the education started. However, the self-perceived knowledge regarding food and nutrition for sick elderly as well as the knowledge of assessing nutritional status, increased. The interviews with the elderly receiving home care showed that they most often were satisfied with food service and food provided by the home care services. Usually, the elderly reported to consume breakfast, dinner (at noon), and an evening meal along with snack meals once or twice a day. Ready made and home delivered warm meals were the recipients’ first option over meals prepared by the personnel in recipients home. Ready made and home delivered cold meals (to be heated later) were the least preferred meal. For the elderly that had help from the homecare services with the evening meal, this consisted frequently of a prepared sandwich to be stored in the fridge until consumption time. Almost all of the personnel and every third elderly believed that two cooked meals should be offered every day. The reported intake from the elderly showed that there was a risk for a deficient intake of energy and nutrients. Almost 30% of the caretakers were considered underweight. The majority of the personnel agreed totally or partly that assessment of the nutritional status should be performed at all elderly to receive home care. Such a nutritional assessment should be a base for the nutritional treatment. In the present project, the caretakers have, for example, been offered to join personnel and participate in shopping the food, to get assistance with preparation of snack meals and having meals together with others. CONCLUSIONS: The prerequisite to manage on your own and to have a meaningful life, are an adequate intake of energy and nutrients, among other factors. The meal can, and should take time. Food and nutrition should be prioritized to an even larger extent by decision makers in Malmö as in other municipalities. This enables personnel to create a joyful meal situation for the elderly and an optimal state of nutrition. It is important to change and extend the options to include an evening meal, the possibility to get assisted snack meals permitted by care managers, and to establish routines that are systematic and uniform regarding diet and nutrition. This project showed that the suggested changes are possible to implement. The changes are of great importance to all elderly receiving home care, and especially elderly suffering from underweight.
6.	Andersson, Marie, 1974-, et al. (författare) Correction : Maternal Transfer of the Cyanobacterial Neurotoxin β-N-Methylamino-L-Alanine (BMAA) via Milk to Suckling Offspring 2015 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:10 Tidskriftsartikel (refereegranskat)
7.	Andersson, Marie, et al. (författare) Maternal Transfer of the Cyanobacterial Neurotoxin beta-N-Methylamino-L-Alanine (BMAA) via Milk to Suckling Offspring 2013 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:10, s. e78133- Tidskriftsartikel (refereegranskat)abstract The cyanobacterial neurotoxin beta-N-methylamino-L-alanine (BMAA) has been implicated in the etiology of neurodegenerative disease and proposed to be biomagnified in terrestrial and aquatic food chains. We have previously shown that the neonatal period in rats, which in humans corresponds to the last trimester of pregnancy and the first few years of age, is a particularly sensitive period for exposure to BMAA. The present study aimed to examine the secretion of C-14-labeled L-and D-BMAA into milk in lactating mice and the subsequent transfer of BMAA into the developing brain. The results suggest that secretion into milk is an important elimination pathway of BMAA in lactating mothers and an efficient exposure route predominantly for L-BMAA but also for D-BMAA in suckling mice. Following secretion of [C-14] L-BMAA into milk, the levels of [C-14] L-BMAA in the brains of the suckling neonatal mice significantly exceeded the levels in the maternal brains. In vitro studies using the mouse mammary epithelial HC11 cell line confirmed a more efficient influx and efflux of L-BMAA than of D-BMAA in cells, suggesting enantiomer-selective transport. Competition experiments with other amino acids and a low sodium dependency of the influx suggests that the amino acid transporters LAT1 and LAT2 are involved in the transport of L-BMAA into milk. Given the persistent neurodevelopmental toxicity following injection of L-BMAA to neonatal rodent pups, the current results highlight the need to determine whether BMAA is enriched mother's and cow's milk.
8.	Annas, Anita, et al. (författare) Basal and induced EROD activity in the chorioallantoic membrane during chicken embryo development 1999 Ingår i: Environmental Toxicology and Pharmacology. - 1382-6689 .- 1872-7077. ; 8:1, s. 49-52 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract The chorioallantoic membrane (CAM) is a highly vascularized tissue that takes part in the respiratory exchange of gases through the eggshell. Although the CAM may be exposed to environmental contaminants, its response to pollutants has not been studied. We examined the cytochrome P4501A (CYP1A)-catalyzed deethylation of 7-ethoxyresorufin (EROD) in the CAM during chicken embryo development. EROD was constitutively present and was inducible by the aryl hydrocarbon (Ah) receptor agonist 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126). Our results suggest the CAM as a first line of defence of the avian embryo against toxic compounds, but also as a target for CYP1A-activated chemicals.
9.	Annas, Anita, et al. (författare) Induction of ethoxyresorufin O-deethylase (EROD) and endothelial activation of the heterocyclic amine Trp-P-1 in bird embryo hearts 1998 Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 72:7, s. 402-410 Tidskriftsartikel (refereegranskat)abstract The xenobiotic-metabolizing activity of avian heart was investigated in chicken and Eider duck embryos exposed to aryl hydrocarbon (Ah) receptor agonists in ovo. Both beta-naphthoflavone (BNF) and 3,3',4,4',5-pentachlorobiphenyl (PCB 126) induced 7-ethoxyresorufin O-deethylase (EROD) activities in chicken embryo hearts whereas Eider duck embryos only responded to BNF. The differential responses of chicken and Eider duck embryos were used to examine the involvement of Ah receptor-mediated enzyme induction in the activation of the environmental and food mutagen 3-amino- 1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1). As determined by light microscopic autoradiography, there was a highly selective binding of non-extractable 3H-Trp-P-1-derived radioactivity in endothelial cells of large vessels and capillaries in hearts of BNF- and PCB 126-treated chicken embryos. No binding occurred at these sites in vehicle-treated controls. There was also a strong endothelial binding of 3H-Trp-P-1 in hearts of BNF-treated Eider duck embryos whereas no binding occurred in hearts of PCB 126-treated Eider duck embryos. A positive correlation between induction of EROD activity and covalent binding of 3H-Trp-P-1 to protein in heart homogenates from BNF- and PCB 126-treated chicken and Eider duck embryos was also observed. The results suggest a cytochrome P450 1A (CYP1A)-mediated activation of Trp-P-1 in avian heart endothelial cells although involvement of other Ah receptor-regulated enzymes is also possible. We propose that heart endothelial cells may be targets for bioactivation and toxicity of environmental contaminants in birds exposed to Ah receptor agonists.
10.	Askling, J, et al. (författare) Haematopoietic malignancies in rheumatoid arthritis : lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists 2005 Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 64:10, s. 1414-1420 Tidskriftsartikel (refereegranskat)abstract BACKGROUND:Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, and maybe also of leukaemia and multiple myeloma. The effect of tumour necrosis factor (TNF) antagonists on lymphoma risk and characteristics is unclear.OBJECTIVE:To assess expected rates and relative risks of haematopoietic malignancies, especially those associated with TNF antagonists, in large population based cohorts of patients with RA.METHODS:A population based cohort study was performed of patients with RA (one prevalent cohort (n = 53,067), one incident cohort (n = 3703), and one TNF antagonist treated cohort 1999 through 2003 (n = 4160)), who were linked with the Swedish Cancer Register. Additionally, the lymphoma specimens for the 12 lymphomas occurring in patients with RA exposed to TNF antagonists in Sweden 1999 through 2004 were reviewed.RESULTS:Study of almost 500 observed haematopoietic malignancies showed that prevalent and incident patients with RA were at increased risk of lymphoma (SIR = 1.9 and 2.0, respectively) and leukaemia (SIR = 2.1 and 2.2, respectively) but not of myeloma. Patients with RA treated with TNF antagonists had a tripled lymphoma risk (SIR = 2.9) compared with the general population. After adjustment for sex, age, and disease duration, the lymphoma risk after exposure to TNF antagonists was no higher than in the other RA cohorts. Lymphomas associated with TNF antagonists had characteristics similar to those of other RA lymphomas.CONCLUSION:Overall, patients with RA are at equally increased risks for lymphomas and leukaemias. Patients with RA treated with TNF antagonists did not have higher lymphoma risks than other patients with RA. Prolonged observation is needed to determine the long term effects of TNF antagonists on lymphoma risk.
11.	Askling, Johan, et al. (författare) Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden 2005 Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 52:7, s. 1986-1992 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE:Because treatment with tumor necrosis factor (TNF) antagonists may increase the risk of tuberculosis (TB), and because knowledge of the risk of TB in rheumatoid arthritis (RA) not treated with biologics is scarce and of uncertain generalizability to low-risk populations, this study sought to determine the risk of TB among Swedish patients with RA.METHODS:Using data from Swedish nationwide and population-based registers and data from an ongoing monitoring program of TNF antagonists, the relative risks of TB in patients with RA (versus the general population) and of TB associated with TNF antagonists (versus RA patients not treated with biologics) were determined by comparing the incidence of hospitalization for TB in 3 RA cohorts and 2 general population cohorts from 1999 to 2001. We also reviewed the characteristics of all reported cases of TB in RA patients treated with TNF antagonists in Sweden and calculated the incidence of TB per type of TNF antagonist between 1999 and 2004.RESULTS:During 1999-2001, RA patients who were not treated with TNF antagonists were at increased risk of TB versus the general population (relative risk 2.0, 95% confidence interval [95% CI] 1.2-3.4). RA patients treated with TNF antagonists had a 4-fold increased risk of TB (relative risk 4.0, 95% CI 1.3-12) versus RA patients not treated with TNF antagonists. The reported TB cases during 1999-2004 in RA patients exposed to TNF antagonists (9 infliximab, 4 etanercept, 2 both) were predominantly pulmonary. TB occurred up to 3 years following the start of treatment.CONCLUSION:Irrespective of whether TNF antagonists are administered, Swedish patients with RA are at increased risk of TB. During 1999-2001, TNF antagonists were associated with an increased risk of TB, up to 4-fold in magnitude. This increased risk may persist over time during treatment and is related to both infliximab and etanercept.
12.	Askling, J, et al. (författare) Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists 2005 Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 64:10, s. 1421-1426 Tidskriftsartikel (refereegranskat)abstract BACKGROUND:Existing studies of solid cancers in rheumatoid arthritis (RA) reflect cancer morbidity up until the early 1990s in prevalent cohorts admitted to hospital during the 1980s.OBJECTIVE:To depict the cancer pattern of contemporary patients with RA, from updated risk data from prevalent and incident RA populations. To understand the risk of solid cancer after tumour necrosis factor (TNF) treatment by obtaining cancer data from cohorts treated in routine care rather than trials.METHODS:A population based study of three RA cohorts (one prevalent, admitted to hospital 1990-2003 (n = 53,067), one incident, diagnosed 1995-2003 (n = 3703), and one treated with TNF antagonists 1999-2003 (n = 4160)), which were linked with Swedish nationwide cancer and census registers and followed up for cancer occurrence through 2003.RESULTS:With 3379 observed cancers, the prevalent RA cohort was at marginally increased overall risk of solid cancer, with 20-50% increased risks for smoke related cancers and +70% increased risk for non-melanoma skin cancer, but decreased risk for breast (-20%) and colorectal cancer (-25%). With 138 cancers, the incident RA cohort displayed a similar cancer pattern apart from non-decreased risks for colorectal cancer. TNF antagonist treated patients displayed solid cancer (n = 67) risks largely similar to those of other patients with RA.CONCLUSION:The cancer pattern in patients treated with TNF antagonists mirrors those of other contemporary as well as historic RA cohorts. The consistent increase in smoking associated cancers in patients with RA emphasises the potential for smoking cessation as a cancer preventive measure in RA.
13.	Askling, Johan, et al. (författare) Time-dependent increase in risk of hospitalisation with infection among Swedish RA patients treated with TNF antagonists 2007 Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 66:10, s. 1339-1344 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES:The degree to which treatment with tumour necrosis factor (TNF) antagonists may be associated with increased risks for serious infections is unclear. An observational cohort study was performed using prospectively collected data from the Swedish Biologics Register (ARTIS) and other national Swedish registers.METHODS:First, in the ARTIS, all 4167 rheumatoid arthritis (RA) patients starting TNF antagonist treatment between 1999 and 2003 were identified. Secondly, in the Swedish Inpatient Register, all individuals hospitalised for any reason and who also carried a diagnosis of RA, between 1964 and 2003 (n = 44 946 of whom 2692 also occurred in ARTIS), were identified. Thirdly, in the Swedish Inpatient Register, all hospitalisations listing an infection between 1999 and 2003 were identified. By cross-referencing these three data sets, RRs for hospitalisation with infection associated with TNF antagonist treatment were calculated within the cohort of 44 946 RA patients, using Cox regression taking sex, age, geography, co-morbidity and use of inpatient care into account.RESULTS:Among the 4167 patients treated with TNF antagonists, 367 hospitalisations with infections occurred during 7776 person-years. Within the cohort of 44 496 RA patients, the RR for infection associated with TNF antagonists was 1.43 (95% CI 1.18 to 1.73) during the first year of treatment, 1.15 (95% CI 0.88 to 1.51) during the second year of treatment, and 0.82 (95% CI 0.62 to 1.08) for subjects remaining on their first TNF antagonist treatment after 2 years.CONCLUSION:Treatment with TNF antagonists may be associated with a small to moderate increase in risk of hospitalisation with infection, which disappears with increasing treatment duration.
14.	Bahrami, Fariba, et al. (författare) Persistent Olfactory Mucosal Metaplasia and Increased Olfactory Bulb Glial Fibrillary Acidic Protein Levels Following a Single Dose of Methylsulfonyl-dichlorobenzene in Mice: Comparison of the 2,5- and 2,6-Dichlorinated Isomers 2000 Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X .- 1096-0333. ; 162:1, s. 49-59 Tidskriftsartikel (refereegranskat)abstract Histopathology was used to characterize long-term toxic effects in the olfactory system following a single ip dose (4–65 mg/kg) of methylsulfonyl-2,6-dichlorobenzene, (2,6-(diCl-MeSO2-B)), in female NMRI mice. The effects of 2,6-(diCl-MeSO2-B) and its 2,5-chlorinated isomer, (2,5-(diCl-MeSO2-B)), on the levels of glial fibrillary acidic protein (GFAP; a biomarker for neurotoxicity) in different brain regions were examined by an enzyme-linked immunosorbent assay (ELISA). The histopathologic effects of 2,6-(diCl-MeSO2-B) were dose-, time-, and tissue-dependent. At the highest doses (16–65 mg/kg), the initial effect of 2,6-(diCl-MeSO2-B) was necrosis of the Bowman's glands, followed by a sequence of secondary events including degeneration of the olfactory neuroepithelium, repopulation of the basement membrane by a ciliated respiratorylike epithelium, fibrosis and ossification in the lamina propria, formation of bilateral polyps, angiogenesis, and disappearance of nerve bundles. Remodeling was most pronounced in the dorsal meatus of the olfactory mucosa and persisted for the duration of the experiment (46 weeks). A dose-dependent induction of GFAP in the olfactory bulb of mice treated with 2,6-(diCl-MeSO2-B) was observed at all doses examined (16–65 mg/kg). GFAP levels were highest 2 weeks after treatment (eightfold induction at 65 mg/kg) and then gradually decreased to normal within 26 weeks. The 2,5-substituted isomer (65 mg/kg) did not induce GFAP in the olfactory bulb and or toxicity in the olfactory mucosa. In conclusion, a single dose of 2,6-(diCl-MeSO2-B) results in persistent metaplasia and remodeling of the olfactory mucosa, and a long-lasting but transient induction of GFAP in the olfactory bulb. It is proposed that methylsulfonyl-2,6-dichlorobenzene may serve as an experimental tool with a unique ability to produce persistent primary and/or secondary lesions in the olfactory system of mice.
15.	Belfrage, Anna Karin, et al. (författare) Discovery of pyrazinone based compounds that potently inhibit the drug resistant enzyme variant R155K of the hepatitis C virus NS3 protease 2016 Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 24:12, s. 2603-2620 Tidskriftsartikel (refereegranskat)abstract Herein, we present the design and synthesis of 2(1H)-pyrazinone based HCV NS3 protease inhibitors with variations in the C-terminus. Biochemical evaluation was performed using genotype 1a, both the wildtype and the drug resistant enzyme variant, R155K. Surprisingly, compounds without an acidic sulfonamide retained good inhibition, challenging our previous molecular docking model. Moreover, selected compounds in this series showed nanomolar potency against R155K NS3 protease; which generally confer resistance to all HCV NS3 protease inhibitors approved or in clinical trials. These results further strengthen the potential of this novel substance class, being very different to the approved drugs and clinical candidates, in the development of inhibitors less sensitive to drug resistance.
16.	Belfrage, Anna Karin, 1977-, et al. (författare) Pan-NS3 protease inhibitors of hepatitis C virus based on an R3-elongated pyrazinone scaffold 2018 Ingår i: European Journal of Medicinal Chemistry. - : Elsevier. - 0223-5234 .- 1768-3254. ; 148, s. 453-464 Tidskriftsartikel (refereegranskat)abstract Herein, we present the design and synthesis of 2(1H)-pyrazinone based HCV NS3 protease inhibitors and show that elongated R-3 urea substituents were associated with increased inhibitory potencies over several NS3 protein variants. The inhibitors are believed to rely on beta-sheet mimicking hydrogen bonds which are similar over different genotypes and current drug resistant variants and correspond to the beta-sheet interactions of the natural peptide substrate. Inhibitor 36, for example, with a urea substituent including a cyclic imide showed balanced nanomolar inhibitory potencies against genotype la, both wild-type (K-i=30 nM) and R155K (K-i=2 nM), and genotype 3a (K-i=5 nM).
17.	Bergkvist, Viktor, et al. (författare) Location in Work Practices. The Social Shaping of a Personal Digital Assistant 2002 Konferensbidrag (refereegranskat)
18.	Binder, Thomas, et al. (författare) Democratic design experiments : between parliament and laboratory 2015 Ingår i: CoDesign - International Journal of CoCreation in Design and the Arts. - : Taylor & Francis. - 1571-0882 .- 1745-3755. ; 11:3-4, s. 152-165 Tidskriftsartikel (refereegranskat)abstract For more than four decades, participatory design has provided exemplars and concepts for understanding the democratic potential of design participation. Despite important impacts on design methodology, participatory design has, however, been stuck in a marginal position as it has wrestled with what has been performed and accomplished in participatory practices. In this article, we discuss how participatory design may be reinvigorated as a design research programme for democratic design experiments in the light of the decentring of human-centredness and the foregrounding of collaborative representational practices offered by the ANT tradition in the tension between a parliament of things and a laboratory of circulating references.
19.	Brandt, Eva, et al. (författare) Co-design Events : Driving Innovation by a series of events (Programmatic vision) 2010 Ingår i: Rehearsing the Future. - : The Danish Design School Press. - 8792016162 ; , s. 70-73 Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract One powerful co-design event is worth a thousand hours of individual work! Driving innovation as a series of co-design events helps mobilize and involve all stakeholders to explore present everyday practices and to sketch new possible futures. But what makes a co-design event powerful? And why are series of events better than a sequence of deliverables and milestones in keeping innovation on track?
20.	Brandt, Eva, et al. (författare) Design Lab : re-thinking what and how to design 2005 Ingår i: Design spaces. - Helsingfors : Edita Publishing Oy. ; , s. 34-43 Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract Over the last decades there has been a dramatic change in the design agenda within the field of IT design. With the increase of mobile and wireless devices and the massive expansion of Internet availability the classic object of design - is about to vanish. Even if we conceive the setting where information technology is used as a 'system', this system can hardly be seen as the outcome of a system design process. Arguably, IT design is today guided by new design agendas. Ubiquitous computing and from the user side information ecologies seem to be more appropriate labels for the emerging technology. The objects of design has correspondingly been changing from systems to devices, tools or information appliances. This radical opening of the question of what to design has led to an apparent confusion on how to design. Just as the field of information systems is about to mature with a broad and widely accepted repertoire of design approaches and methods, ranging from workflow analysis to user involvement, this battery of approaches is loosing ground in favor of more techno-centric explorations, such as Tangible Computing. In our view there seem to be a growing divide between mainly North American contributions to IT design emphasizing new information technology concepts such as ubiquitous computing, tangible interaction and augmented reality, and mainly European contributions emphasizing the role of particular information technology applications in the light of in-depth studies of the potential contexts of use.
21.	Brandt, Eva, et al. (författare) Design Lab : re-thinking what and how to design 2005 Ingår i: Design spaces. - Helsingfors : Edita Publishing Oy. ; , s. 34-43 Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract Over the last decades there has been a dramatic change in the design agenda within the field of IT design. With the increase of mobile and wireless devices and the massive expansion of Internet availability the classic object of design - is about to vanish. Even if we conceive the setting where information technology is used as a 'system', this system can hardly be seen as the outcome of a system design process. Arguably, IT design is today guided by new design agendas. Ubiquitous computing and from the user side information ecologies seem to be more appropriate labels for the emerging technology. The objects of design has correspondingly been changing from systems to devices, tools or information appliances. This radical opening of the question of what to design has led to an apparent confusion on how to design. Just as the field of information systems is about to mature with a broad and widely accepted repertoire of design approaches and methods, ranging from workflow analysis to user involvement, this battery of approaches is loosing ground in favor of more techno-centric explorations, such as Tangible Computing. In our view there seem to be a growing divide between mainly North American contributions to IT design emphasizing new information technology concepts such as ubiquitous computing, tangible interaction and augmented reality, and mainly European contributions emphasizing the role of particular information technology applications in the light of in-depth studies of the potential contexts of use.
22.	Brandt, Eva, et al. (författare) Formatting Design Dialogues - Games and Participation 2008 Ingår i: CoDesign - International Journal of CoCreation in Design and the Arts. - : Taylor & Francis. - 1571-0882 .- 1745-3755. ; 4:1, s. 51-64 Tidskriftsartikel (refereegranskat)abstract This article discusses design games as a particular genre for formatting design dialogues. In the first part of the article we review the participatory design literature for game-oriented framings of co-design. We look at what constitutes game and play, we discuss other authors’ use of games in collaborative settings and finally we examine the board game as a particularly interesting game format. In the second part of the article we present and discuss two board games: the User Game and the Landscape Game. We show how these games respond to particular challenges, and how they have interesting characteristics in being both ‘as-if’ worlds to explore and shared representations of what the players accomplish. In the last section of the article we discuss how new games may be designed and played and what makes a good design game.
23.	Brandt, Eva, et al. (författare) From a blank slate or a full table? : kicking off innovation by exploring the well-known 2010 Ingår i: Rehearsing the Future. - : The Danish Design School Press. - 8792016162 ; , s. 74-79 Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract Innovation never starts from a blank slate - rather many contributors bring previous experiences, current practices and personal interests to the table. By providing materials that support remembering, sharing and exploring these collaboratively in different ways, we can render them "strangely familiar" and thus fruitful for innovation processes.
24.	Brandt, Eva, et al. (författare) XLAB 2011 Bok (övrigt vetenskapligt/konstnärligt)abstract Research at design schools or research conducted by people with a professional training in design or architecture is not necessarily different from research of for example art history, media studies or anthropology. Nevertheless we see new research topics and new research methodologies emerge as designers begin to employ their professional gaze within the world of research. Research-through-design, practice-based research or design-led research are all among the new labels that characterize such research that strives to bring design competences into play in design research. This book comes out o the XLAB project - one attempt to get hold of what such design research may be and how it can contribute to the production of knowledge. The XLAB project sought to capture design research and particularly the design experiment not through a theoretical or methodological approach, but through a practical exploration of the practice of design researchers. This happened through a series of three one-day workshops with researchers and research students.
25.	Brinton, Louise A, et al. (författare) Anthropometric and Hormonal Risk Factors for Male Breast Cancer: Male Breast Cancer Pooling Project Results. 2014 Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 106:3, s. 465-465 Tidskriftsartikel (refereegranskat)abstract The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors.
26.	Brittebo, Eva, 1951-, et al. (författare) Bioactivation and effects of environmental pollutants in human and rodent blood vessel endothelial cells 2012 Ingår i: Organohalogen compound database (http://www.dioxin20xx.org/ohc_database_search.htm). Konferensbidrag (refereegranskat)abstract IntroductionRecent epidemiological studies reveal associations between exposure to environmental pollutants and cardiovascular disorders in humans. Elevated serum concentrations of polychlorinated biphenyls (PCBs) have for instance been associated with cardiovascular risk factors such as hypertension (1-3). Exposure to the carbonate plastic monomer bisphenol A (BPA) has been associated with an increased incidence of cardiovascular disease and atherogenic changes in the vascular wall (4-6). The contention that the human cardiovascular system is a sensitive target for toxic chemicals gain support from our earlier and recent experimental studies in rodents, birds and fish, as well as in cultured human primary endothelial cells. It is also compatible with earlier observations that certain polycyclic aromatic hydrocarbons (PAHs) are environmental carcinogens that may also contribute to atherosclerosis in mice and birds (7,8).In this presentation we will briefly discuss effects of Ah receptor (AhR) agonists (e.g. the coplanar PCB126 or BNF, ß-naphthoflavone) on the expression of cytochrome P450 (CYP)1 enzymes in various endothelia in rodents in vivo or ex vivo, as well as in cultured human umbilical vein endothelial cells (HUVEC). The CYP1-dependent bioactivation and irreversible binding of prototype polyaromatic hydrocarbons (PAH) and heterocyclic amines such as benzo(a)pyrene (BaP), 7,12-dimethyl- benz(a)anthracene (DMBA) and 3-amino-1,4-dimethyl-5H-pyrido- [4,3-b]indole (Trp-P1) in these endothelia will be reviewed. We will also report how PCB126 affects vasoactive factors in HUVEC, and how these effects are modulated by physiological 17ß-oestradiol concentrations. Some effects of PCB126, 1-nitropyrene (1-NP) and bisphenol A (BPA) on biomarkers for endothelial dysfunction, cell stress and DNA damage in HUVEC will finally be presented.Material and methodsHuman umbilical vein endothelial cells (HUVEC) were purchased from Science Cell Research laboratories, Carlsbad, CA. C57Bl mice and Wistar or Sprague Dawley rats were purchased from various suppliers. All animal experiments were approved by the Local Ethical Committee for Research on Animals in Uppsala and the studies followed the guidelines laid down by the Swedish and European Union legislation on animal experimentation. Rodents, tissue-slices and cultured cells were treated with model chemicals as previously described. Tape section and light microscopy autoradiographic imaging using 3H-labelled BaP, DMBA and Trp-P-1 and immunohistochemistry was performed as previously described (9-19). Precision-cut tissue slices for in vitro autoradiography were prepared as described in (14) and the slices were incubated with various 3H-labelled chemicals. HUVEC were exposed to various compounds and the detection of biomarkers of endothelial dysfunction, DNA damage were performed as described (20-22). Finally, female Fischer rats were exposed to BPA (0.025, 0.25 and 2.5 mg/l) and fructose (50 g/l) in the drinking water from 5 to 15 weeks of age to mimic human exposure (unpublished data).Results and discussionCo-localization of CYP1A1 expression and BaP, DMBA and Trp-P-1 adduct formation in endothelial linings As demonstrated by immunohistochemistry, a high CYP1A immunoreactivity occurred in capillaries of the heart, skeletal muscle, uterus and in blood-brain interfaces such as the leptomeninges and plexus choroideus, whereas no expression was observed for instance in cerebral capillary endothelial cells of mice treated with AhR agonists (9-11). No, or very low constitutive immunoreactivities were observed in these endothelia in vehicle-treated animals. No basal or induced CYP1B1 expression was observed in endothelial cells, while a weak CYP1B1 immunostaining was detected in the muscle layer of small arteries. It should be noted that in subcellular preparations of whole organs, e.g. heart and brain, the CYP1A1 in endothelial cells is diluted due to cells that do not express high levels of CYP1A1, for examples myocytes or neurons, in excess. A cell-specific metabolism in endothelial cells may therefore remain undetected due to the presence of metabolically inactive cells. In order to detect minor sites of bioactivation such as endothelial linings we employed light microscopic autoradiographic imaging to examine the bioactivation and subsequent irreversible binding of the radiolabelled prototype toxicants in tissues of animals pretreated with AhR-agonists. As determined by light microscopic autoradiography of AhR-agonist-treated mice exposed to 3H-labelled BaP, DMBA or Trp-P-1 and birds exposed to 3H-Trp-P-1 a significant accumulation of non-extractable radioactivity occurred in endothelial linings (9-18). The bound radioactivity occurred in the nuclei and the perinuclear cytoplasm, suggesting that the autoradiograms depict both DNA- and protein-bound adducts. Since the binding sites of 3H-labelled BaP, DMBA or Trp-P-1 corresponded with the sites of CYP1A1 induction, we concluded that rodents express a constitutively low but highly inducible and functional CYP1A1 in endothelial cells. The binding of reactive metabolites in endothelial cells exceeded the binding in all other cell types in AhR-agonist treated mice and was abolished by pretreatment with the CYP1A1 inhibitor ellipticine, supporting a CYP1A1-catalysed metabolic activation in situ to a reactive species (9, 10,12). These findings imply that there is a preferential CYP1A1-catalysed formation of reactive metabolites from all three carcinogens in endothelial cells expressing high CYP1A1 levels. Interestingly, however, carcinogenesis in endothelial cells is a relative rare finding, suggesting that degenerative lesions and cell death may be more prevalent responses to metabolism-activated carcinogens/mutagens in these cells. Experiments with 3H-DMBA and 3H-Trp-P-1 in HUVEC confirmed that AhR-agonists induced an increased bioactivation, suggesting that also human endothelial cells should be targets for toxicity of reactive intermediates formed from CYP1A1- activated carcinogens/mutagens (17-18). This conclusion is supported by immunohistochemical studies on the heavily vascularized human endometrium demonstrating an expression of CYP1A1 and CYP1B1 protein in and around human endometrial blood vessels, although a large interindividualvariation was observed (19). None of the endometrial biopsy samples displayed vascular expression of CYP2A6, CYP2B6, CYP2C8/2C9/2C19, CYP2D6, or CYP3A4/5 protein.Effects of PCB 126, 1-NP, and BPA on biomarkers of endothelial dysfunction and cell stress in endothelial cells In vitro studies demonstrated that PCB126 increased the levels of vasoconstriction factors and decreased the levels of vasodilating factors in cultured HUVEC in a fashion that is characteristic for endothelial dysfunction related to human hypertension. The study showed that the co-planar PCB126 induced expression of the endothelium-derived vasoconstriction factor COX-2 and stimulated formation of the vasoconstrictor prostaglandin PGF2 via the AhR in HUVEC (20). COX-2 is known to play a role in hypertension by catalysing the formation of vasoconstriction prostaglandins and by stimulating reactive oxygen species (ROS) production. Further studies demonstrated that PCB126 increased the production of the vasoconstriction prostaglandin PGF2 and ROS in HUVEC. The relationship between increased ROS production and human hypertension is well established, ROS promotes vasoconstriction by stimulating the production of vasoconstriction prostaglandins and by reducing bioavailability of the vasorelaxing factor NO. Indeed, exposure to PCB126 slightly reduced the production of NO in HUVEC. Furthermore, the PCB126-induced mRNA expressions of CYP1A1, CYP1B1 and COX-2 in HUVEC were enhanced in the presence of physiological levels of 17- estradiol. This suggests that increased levels of oestrogen stimulate AhR-dependent transcription of genes previously associated with endothelial dysfunction and hypertension.In another study we have examined the effects of a nitrated PAH, 1-nitropyrene, that is abundant in diesel exhausts (21). The results revealed that 1-NP induced DNA damage, increased levels of ROS and increased protein expression of the endoplasmic reticulum stress chaperone GRP78 in cultured HUVEC. Induction of CYP1A1 by PCB126 as well as inhibition of nitroreductive metabolism by dicoumarol attenuated the induction of DNA damage, intracellular ROS levels and GRP78 expression. This suggests that the effects of 1-NP on HUVEC were mediated by metabolites mainly formed at nitroreduction and not by CYP1-dependent bioactivation to reactive intermediates.Recent in vitro studies demonstrated that bisphenol A increased the mRNA expression of genes that regulate vasoconstriction and angiogenesis in HUVEC (eNOS, VEGF, VEGFR2, connexin 43 and ACE1) and in human cardiomyocytes (eNOS and ACE1) (22). The results also showed that BPA increased the expression of P-eNOS(ser1177) and the production of NO in HUVEC. NO is the main effector molecule in angiogenesis downstream of VEGF. Based on the findings that BPA increase the expression of proangiogenic factors we investigated whether BPA could stimulate in vitro angiogenesis in HUVEC using the endothelial tube formation assay. The results demonstrated that BPA increased HUVEC tube formation suggesting that BPA can act directly on the endothelium and stimulate angiogenesis. Long-term exposure in rats revealed that environmentally relevant levels of BPA, increased the cardiac mRNA expression of genes that regulate vasoconstriction and angiogenesis. Ten weeks exposure of rats from preadolescence to adulthood to BPA in the drinking water increased theexpression of eNOS, VEGF, VEGFR2 and ACE1 in the heart. Taken together, the genes that were upregulated in rat cardiac tissues in vivo were also upregulated in human endothelial cells and cardiomyocytes in vitro. The heart is a heavily vascularized t
27.	Cook, Michael B, et al. (författare) Tobacco and Alcohol in Relation to Male Breast Cancer: An Analysis of the Male Breast Cancer Pooling Project Consortium. 2015 Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 24:3, s. 520-531 Tidskriftsartikel (refereegranskat)abstract Background: The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined. Methods: The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case-control and 10 cohort studies. Individual participant data were harmonized and pooled. Unconditional logistic regression was used to estimate study design-specific (case-control/cohort) odds ratios (OR) and 95% confidence intervals (CI), which were then combined using fixed effects meta-analysis. Results: Cigarette smoking status, smoking pack-years, duration, intensity, and age at initiation were not associated with male breast cancer risk. Relations with cigar and pipe smoking, tobacco chewing, and snuff use were also null. Recent alcohol consumption and average grams of alcohol consumed per day were also not associated with risk; only one sub-analysis of very high recent alcohol consumption (>60 grams/day) was tentatively associated with male breast cancer (ORunexposed referent=1.29, 95%CI:0.97-1.71; OR>0-<7 g/day referent=1.36, 95%CI:1.04-1.77). Specific alcoholic beverage types were not associated with male breast cancer. Relations were not altered when stratified by age or body mass index. Conclusions: In this analysis of the Male Breast Cancer Pooling Project we found little evidence that tobacco and alcohol exposures were associated with risk of male breast cancer. Impact: Tobacco and alcohol do not appear to be carcinogenic for male breast cancer. Future studies should aim to assess these exposures in relation to subtypes of male breast cancer.
28.	Debette, Stéphanie, et al. (författare) Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection 2015 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47, s. 78-83 Tidskriftsartikel (refereegranskat)abstract Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year)1. Minor cervical traumas, infection, migraine and hypertension are putative risk factors1–3, and inverse associations with obesity and hypercholesterolemia are described3,4. No confirmed genetic susceptibility factors have been identified using candidate gene approaches5. We performed genome-wide association studies (GWAS) in 1 1,393 CeAD cases and 1 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69–0.82; P = 4.46 × 1 10−10), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 1 × 1 10−3; combined P = 1 1.00 × 1 10−1111). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction6–9. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.
29.	Edelbring, Samuel, PhD, Docent, 1969-, et al. (författare) Interprofessionell simulering är engagerande och relevant [Interprofessional simulation: an engaging and relevant technique for teamwork practice] 2019 Ingår i: Läkartidningen. - Stockholm, Sweden : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 116 Tidskriftsartikel (refereegranskat)abstract Stakeholders in healthcare and education find interprofessional teamwork to be crucial for todays complex healthcare. Consequently, the students need to prepare for future collaboration with other professions. Interprofessional simulation (IPS) is a technique in which several professions can engage together in clinical scenarios. Using a survey we studied the perceived relevance of two IPS settings in which last-year medical and nursing students participated in acute care scenarios. The findings showed that students perceive IPS as being highly relevant and that students from the other profession contributed to their learning. IPS holds promise as a pedagogical tool towards future interprofessional competence. However, pedagogical improvements can be made, and the professional perspectives can be better balanced. Furthermore, in order to equip students with broader interprofessional competence, scenarios should include several professions and a variety of clinical contexts.
30.	Edelbring, Samuel, PhD, Docent, 1969-, et al. (författare) Interprofessionell simulering är engagerande och relevant: Utbildningsstrategi som tränar samverkan över yrkesgränser, visar enkätstudie [Interprofessional simulation: an engaging and relevant technique for teamwork practice] 2019 Ingår i: Läkartidningen. - Stockholm : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 116 Tidskriftsartikel (refereegranskat)abstract Studenter behöver träna på teamarbete och utveckla interprofessionell kompetens för att rustas för framtidens hälso- och sjukvård.Utbildning för interprofessionell samverkan kan ske genom simulering där läkar- och sjuksköterskestudenter möts och agerar tillsammans i patientscenarier. Interprofessionell simulering upplevdes som relevant och engagerande av studenter på två lärosäten. Studenter från den andra professionen bidrog till lärandet. Det finns dock utrymme att ytterligare förbättra det pedagogiska genomförandet, och professionsperspektiven kan balanseras bättre.
31.	Eriksen, Mette Agger, et al. (författare) Taking Design Games Seriously : Re-connecting Situated Power Relations of People and Materials 2014 Ingår i: PDC '14 Proceedings of the 13th Participatory Design Conference: Research Papers;i. - New York, New York, USA : ACM Digital Library. ; , s. 101-110 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Using design games at Participatory Design (PD) events is well acknowledged as a fruitful way of staging participation. As PD researchers, we have many such experiences, and we have argued that design games connect participants and promote equalizing power relations. However, in this paper, we will (self) critically re-connect and reflect on how people (humans) and materials (non-humans) continually participate and intertwine in various power relations in design game situations. The analysis is of detailed situated actions with one of our recent games, UrbanTransition. Core concepts mainly from Bruno Latour’s work on Actor-Network-Theory are applied. The aim is to take design games seriously by e.g. exploring how assemblages of humans and non-humans are intertwined in tacitly-but-tactically staging participa- tion, and opening up for or hindering negotiations and decision-making, thus starting to relate research on various PD techniques and power issues more directly.
32.	Eriksen, Mette Agger, et al. (författare) Workshop : an experiment of reflection on design game qualities and controversies 2013 Ingår i: Nordes 2013. - : The Royal Danish Academy of Fine Arts, Schools of Architecture, Design and Conservation. ; , s. 466-468 Konferensbidrag (refereegranskat)abstract How do various design games format and stage different collaborative inquiry, learning and reflection? At this hands-on workshop, we will collaboratively explore, relate and meta-reflect upon how different design (and learning) games can form part of experimental, co-design (research) processes and practice. Some shared playing of mainly analogue games brought by the workshop organizers and participants will provide the basis for engaging in a game-inspired experiment of collaboratively relating and reflecting upon qualities and controversies of different design games. This reflection experiment will be shaped around predefined and emerging topics.
33.	Fortner, Renée T., et al. (författare) Ovarian cancer risk factors by tumor aggressiveness : An analysis from the Ovarian Cancer Cohort Consortium 2019 Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 145:1, s. 58-69 Tidskriftsartikel (refereegranskat)abstract Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.
34.	Franzén, Anna, et al. (författare) Isomer-specific Bioactivation and Toxicity of Dichlorophenyl Methylsulphone in Rat Olfactory Mucosa 2003 Ingår i: Toxicologic pathology (Print). - : SAGE Publications. - 0192-6233 .- 1533-1601. ; 31:4, s. 364-372 Tidskriftsartikel (refereegranskat)abstract This study aimed to explain the isomer- and site-specific toxic effects of dichlorophenyl methylsulphone in the olfactory mucosa of rats. A single ip dose of the 2,6-chlorinated isomer (16 or 65 mg/kg) induced necrosis preferentially in the Bowman's glands and neuroepithelium in the dorsomedial part of the olfactory region. Only minor damage occurred at this site in rats dosed with the 2,5-chlorinated isomer (65 mg/kg). A strong concentration- and time-dependent covalent binding of the C-14-labeled 2,6-isomer to rat olfactory microsomes was demonstrated. In contrast, no significant covalent binding of the C-14-labeled 2,5-isomer was observed. The cytochrome P450 (CYP) inhibitors metyrapone, tranylcypromine and acetonitrile inhibited covalent binding of the 2,6-isomer to olfactory microsomes. Glutathione (GSH) appeared to play a protective role as a scavenger of a reactive intermediate whereas methyl-GSH did not alter covalent binding to olfactory microsomes. As determined by microautoradiography, binding of the 2,6-chlorinated isomer in the olfactory mucosa was confined to the Bowman's glands. Both isomers showed a low binding to liver microsomes and caused no liver injury. We suggest that a CYP2A-catalyzed activation of the 2,6-chlorinated dichlorophenyl methylsulphone to a reactive intermediate and adduct formation in the Bowman's glands will initiate a site-specific toxicity of this isomer in the olfactory mucosa.
35.	Franzén, Anna, 1974- (författare) Tissue-Selective Activation and Toxicity of Substituted Dichlorobenzenes : Studies on the Mechanism of Cell Death in the Olfactory Mucosa 2005 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The nasal passages are constantly exposed to both air- and bloodborne foreign compounds. In particular, the olfactory mucosa is demonstrated to be susceptible to a variety of drugs and chemicals. In this thesis, mechanisms involved in tissue-selective toxicity in the olfactory mucosa of rodents have been investigated using the olfactory toxicant 2,6-dichlorophenyl methylsulphone (2,6-diClPh-MeSO2) as a model compound. Comparative studies were performed with the non-toxic 2,5-dichlorophenyl methylsulphone (2,5-diClPh-MeSO2) and the reasons for the strikingly different toxicity were investigated. A strong bioactivation and protein adduction of 2,6-diClPh-MeSO2 in olfactory microsomes and S9-fractions of rodents was demonstrated. In contrast, no significant metabolic activation of 2,5-diClPh-MeSO2 was observed and the bioactivation in the liver for both chlorinated isomers was negligible. In vitro studies with recombinant yeast cell microsomes expressing mouse cytochrome P450 2A5 (CYP2A5) demonstrated a metabolic activation of 2,6-diClPh-MeSO2. The 2,6-diClPh-MeSO2-induced lesions and CYP2A5 expression preferentially occurred in Bowman’s glands and sustentacular cells of the olfactory mucosa. A significant depletion of glutathione (GSH) in the olfactory mucosa was demonstrated in vivo, while no changes were observed in the liver. There was a rapid induction of the endoplasmic reticulum (ER)-specific chaperone Grp78, activation of the ER-specific caspase-12 and the downstream caspase-3 in the Bowman’s glands. Electron microscopy revealed swelling of ER and mitochondria and a lost integrity of the Bowman’s glands. Based on these results, the proposed mechanism for 2,6-diClPh-MeSO2-induced toxicity in the olfactory mucosa is bioactivation by CYP2A5 into a reactive intermediate causing protein adduction and GSH-depletion. This is initiating a sequence of downstream events of ER-stress, changes in ion homeostasis, ultrastructural organelle disruption and apoptotic signalling. In spite of the initial apoptotic signals, the terminal phase of apoptosis seemed to be blocked and necrotic features occurred. The predominant expression of CYP2A5 in the olfactory mucosa is proposed to play a key role for the tissue- and cell-specific toxicity induced by 2,6-diClPh-MeSO2.
36.	Glimelius, Bengt, et al. (författare) The Swedish Council on Technology Assessment in Health Care (SBU) systematic overview of chemotherapy effects in some major tumour types - summary and conclusions. 2001 Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 40, s. 135-154 Tidskriftsartikel (refereegranskat)
37.	Granberg, Lizette, et al. (författare) CYP1A1 and CYP1B1 in blood-brain interfaces : CYP1A1-dependent bioactivation of 7,12-dimethylbenz(a)anthracene in endothelial cells. 2003 Ingår i: Drug Metabolism And Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0090-9556 .- 1521-009X. ; 31:3, s. 259-265 Tidskriftsartikel (refereegranskat)abstract Immunohistochemistry and autoradiography were used to identify sites of the cytochrome P450 enzymes (P450) 1A1 and 1B1 expression and activation of 7,12-dimethylbenz(a)anthracene (DMBA), in the brain of rodents pretreated with the aryl hydrocarbon receptor (AhR) agonists beta-naphthoflavone (BNF), 3,3',4,4',5-pentachlorobiphenyl or vehicle. Immunohistochemistry revealed that CYP1A1 was preferentially induced in endothelial cells (EC) in the choroid plexus, in veins in the leptomeninges, and in cerebral veins of AhR agonist-pretreated mice. No induction occurred in cerebral capillary EC. In vehicle-treated mice no localization of CYP1A1 in EC was observed. CYP1B1 was expressed in smooth muscle cells of arteries in the leptomeninges, in cerebral arteries/arterioles and to a low extent in ependymal cells of AhR agonist- and vehicle-treated mice. No CYP1B1 was detected in capillary loops of the choroid plexus or in cerebral capillaries. Following administration of [(3)H]DMBA to BNF-pretreated mice, a marked irreversible binding in EC of the choroid plexus and of veins in the leptomeninges was observed but not in cerebral capillaries. In vehicle-treated mice, there was no [(3)H]DMBA-binding at these sites. Furthermore, a high level of irreversibly bound [(3)H]DMBA occurred in EC at these sites in precision-cut mouse/rat brain slices and in excised blood-brain interfaces incubated with [(3)H]DMBA. Since [(3)H]DMBA binding sites corresponded with the sites of CYP1A1 induction, we conclude that rodents express a constitutively low but highly inducible and functional CYP1A1 in EC of some of the blood-brain interfaces. The role of CYP1A1/1B1 and environmental pollutants in the etiology of cerebrovascular disease needs further consideration.
38.	Granberg, Lizette, et al. (författare) CYP1A1 and CYP1B1 in blood-brain interfaces: CYP1A1-dependent bioactivation of 7,12 dimethylbenz(a)anthracene (DMBA) in endothelial cells 2003 Ingår i: Drug Met. Disp.. ; 31, s. 259- Tidskriftsartikel (refereegranskat)
39.	Harrie, Lars, et al. (författare) Some strategic national initiatives for the Swedish education in the geodata field 2014 Ingår i: Proceedings of the AGILE'2014 International Conference on Geographic Information Science. - : AGILE Digital Editions. - 9789081696043 Konferensbidrag (refereegranskat)abstract This paper describes national cooperation in Sweden launched by its universities and authorities, aimed at improving geodata education. These initiatives have been focused upon providing common access to geodata, the production of teaching materials in Swedish and organizing annual meetings for teachers. We argue that this type of cooperation is vital to providing high quality education for a poorly recognized subject in a country with a relatively small population.
40.	Heath, Alicia K., et al. (författare) Diet-wide association study of 92 foods and nutrients and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study 2022 Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 151:11, s. 1935-1946 Tidskriftsartikel (refereegranskat)abstract It is unclear whether diet, and in particular certain foods or nutrients, are associated with lung cancer risk. We assessed associations of 92 dietary factors with lung cancer risk in 327 790 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) per SD higher intake/day of each food/nutrient. Correction for multiple comparisons was performed using the false discovery rate and identified associations were evaluated in the Netherlands Cohort Study (NLCS). In EPIC, 2420 incident lung cancer cases were identified during a median of 15 years of follow-up. Higher intakes of fibre (HR per 1 SD higher intake/day = 0.91, 95% CI 0.87-0.96), fruit (HR = 0.91, 95% CI 0.86-0.96) and vitamin C (HR = 0.91, 95% CI 0.86-0.96) were associated with a lower risk of lung cancer, whereas offal (HR = 1.08, 95% CI 1.03-1.14), retinol (HR = 1.06, 95% CI 1.03-1.10) and beer/cider (HR = 1.04, 95% CI 1.02-1.07) intakes were positively associated with lung cancer risk. Associations did not differ by sex and there was less evidence for associations among never smokers. None of the six associations with overall lung cancer risk identified in EPIC were replicated in the NLCS (2861 cases), however in analyses of histological subtypes, inverse associations of fruit and vitamin C with squamous cell carcinoma were replicated in the NLCS. Overall, there is little evidence that intakes of specific foods and nutrients play a major role in primary lung cancer risk, but fruit and vitamin C intakes seem to be inversely associated with squamous cell lung cancer.
41.	Hudson, Lawrence N, et al. (författare) The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project 2017 Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188 Tidskriftsartikel (refereegranskat)abstract The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
42.	Jezberova, Jitka, et al. (författare) Ubiquity of Polynucleobacter necessarius ssp asymbioticus in lentic freshwater habitats of a heterogenous 2000 km2 area 2010 Ingår i: Environmental Microbiology. - : Wiley. - 1462-2912 .- 1462-2920. ; 12:3, s. 658-669 Tidskriftsartikel (refereegranskat)abstract We present a survey on the distribution and habitat range of Polynucleobacter necessarius ssp. asymbioticus (PnecC), a numerically and functionally important taxon in the plankton of freshwater systems. We systematically sampled stagnant freshwater habitats in a heterogeneous 2000 km2 area, together with ecologically different habitats outside this area. In total, 137 lakes, ponds and puddles were investigated, which represent an enormous diversity of habitats differing, e.g. in depth (< 10 cm - 171 m) and pH (3.9-8.5). PnecC bacteria were detected by cultivation-independent methods in all investigated habitats, and their presence was confirmed by cultivation of strains from selected habitats representing the whole studied ecological range. The determined relative abundance of the subspecies ranged from values close to the detection limit of FISH (0.2%) to 67% (average 14.5%), and the highest observed absolute abundance was 5.3 x 106 cells ml-1. Statistical analyses revealed that the abundance of PnecC bacteria was partially controlled by factors linked to concentrations of humic substances, which support the hypothesis that these bacteria utilize photodegradation products of humic substances. Based on the revealed statistical relationships, an average relative abundance of this subspecies of 20% in global freshwater habitats was extrapolated. Our study provides important implications for the current debate on ubiquity and biogeography in microorganisms.
43.	Johansson, Martin, 1976-, et al. (författare) Partner engaged design : new challanges for workplace design 2002 Ingår i: Proceedings of PDC2002. Konferensbidrag (refereegranskat)abstract The spatial organization of the workplace affects the work going on there. The technology used, changes the work practice. This paper describes a design process where different aspects of workplace design for project-based office work have been combined into one multi-stakeholder project, integrating the spatial aspects, the furniture, the information technology, and the IT-services that are connected to work. To have several different partners with different interests and competencies collaborating in a future oriented design process puts certain demands on the setup of the process and the tools being used. Taking a starting point in existing work practice, we have driven this project with techniques most often used for user-involvement. Scenario building played a crucial role in tying the process together. The concrete result is a completed concept proposal for an actual “office of the future” layout, which integrates advanced information technology and service solutions. The case shows that it is possible to reach innovative consensus-anchored results with the described design method.
44.	Jones, Benedict C, et al. (författare) To which world regions does the valence-dominance model of social perception apply? 2021 Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169 Tidskriftsartikel (refereegranskat)abstract Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
45.	Light, Ann, et al. (författare) Writing participatory design 2016 Ingår i: PDC '16: Proceedings of the 14th Participatory Design Conference: Short Papers, Interactive Exhibitions, Workshops - Volume 2. - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450341363 ; , s. 119-120 Konferensbidrag (refereegranskat)abstract This workshop asks participatory designers and researchers to consider how they write about their work and what role there is for novel approaches to expression, forms drawn from other disciplines, and open and playful texts. As we bring social science and humanities sensibilities to bear on designing with others; as we conduct experiments in infrastructuring and sociotechnical assemblages; as we ask what participation means in different contexts and types of futuring, can we find voice to match our innovations? How do reflexivity, positionality, autobiography and auto-ethnography fit into our reflections on designing? How far are we making our practice even as we write? Is the page a contemplative or collaborative space? Does the tyranny of the conference paper overwrite everything? Join us for this day of reading, writing and discussion about how we tell the stories that matter most to us.
46.	Lim, Nancy Joy, 1980-, et al. (författare) A cartographic framework for visualising flood uncertainties 2018 Annan publikation (övrigt vetenskapligt/konstnärligt)
47.	Lim, Nancy Joy, 1980- (författare) Modelling, mapping and visualisation of flood inundation uncertainties 2018 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Flood maps showing extents of predicted flooding for a given extreme event have wide usage in all types of spatial planning tasks, as well as serving as information material for the public. However, the production processes that these maps undergo (including the different data, methods, models and decisions from the persons generating them), which include both Geographic Information Systems (GIS) and hydraulic modelling, affect the map’s content, and will be reflected in the final map. A crisp flood boundary, which is a common way of representing the boundary in flood maps, may therefore not be the best representation to be used. They provide a false implication that these maps are correct and that the flood extents are absolute, despite the effects of the entire modelling in the prediction output. Hence, this research attempts to determine how flood prediction outputs can be affected by uncertainties in the modelling process. In addition, it tries to evaluate how users understand, utilise and perceive flood uncertainty information. Three main methods were employed in the entire research: uncertainty modelling and analyses; map and geovisualisation development; and user assessment. The studies in this work showed that flood extents produced were influenced by the Digital Elevation Model (DEM) resolution and the Manning’s used. This effect was further increased by the topographic characteristic of the floodplain. However, the performance measure used, which quantify how well a model produces result in relation to a reference floor boundary, had also biases in quantifying outputs. Determining the optimal model output, therefore, depended on outcomes of the goodness-of-fit measures used. In this research, several ways were suggested on how uncertainties can be visualised based on the data derived from the uncertainty assessment and by characterising the uncertainty information. These can be through: dual-ended maps; flood probability maps; sequential maps either highlighting the degrees of certainty (certainty map) or degrees of uncertainty (uncertainty map) in the data; binary maps; overlain flood boundaries from different calibration results; and performance bars. Different mapping techniques and visual variables were used for their representation. These mapping techniques employed, as well as the design of graphical representation, helped facilitate understanding the information by the users, especially when tested during the evaluations. Note though that there were visualisations, which the user found easier to comprehend depending on the task given. Each of these visualisations had also its advantages and disadvantages in communicating flood uncertainty information, as shown in the assessments conducted. Another important aspect that came out in the study was how the users’ background influence decision-making when using these maps. Users’ willingness to take risks depended not only on the map, but their perceptions on the risk itself. However, overall, users found the uncertainty maps to be useful to be incorporated in planning tasks.
48.	Lindström, Veronica, 1978- (författare) Adrenocorticolysis Induced by 3-MeSO2-DDE : Mechanisms of Action, Kinetics and Species Differences 2007 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The DDT metabolite 3-methylsulphonyl-DDE (3-MeSO2-DDE) induces cell death specifically in the adrenal cortex of mice after a cytochrome P45011B1 (CYP11B1)-catalysed bioactivation. This substance is not only an environmental pollutant, but also a suggested lead compound for an improved chemotherapy of adrenocortical carcinoma (ACC). The aim of the thesis was to further investigate this compound in terms of kinetics, cell death mechanisms and species differences. The pharmacokinetics of 3-MeSO2-DDE and the current drug for ACC, o,p’-DDD, was studied during 6 months following a single dose in minipigs. The elimination was slower for 3-MeSO2-DDE than for o,p’-DDD, indicated by a lower clearance and longer t½ in plasma and subcutaneous fat. Both substances remained in fat tissue during the whole study period. Unlike o,p’-DDD, 3-MeSO2-DDE was retained also in liver. The adequacy of the murine adrenocortical cell line Y-1 was evaluated for studies of adrenotoxic compounds. The Y-1 cells proved to be an appropriate test system for future mechanism studies, since CYP-catalysed irreversible binding, inhibited corticosterone production induced by 3-MeSO2-DDE and o,p’-DDD were successfully demonstrated. Cell death of 3-MeSO2-DDE in the mouse adrenal cortex was implied to be necrotic. Early apoptotic signalling (i.e. up-regulation of caspase-9) was observed, although it seemed to be interrupted by ATP-depletion and anti-apoptotic actions by heat shock protein 70, resulting in lack of activation of caspase-3. Using cultured adrenal tissue slices, two not previously studied species were examined ex vivo regarding adrenal binding of 3-MeSO2-[14C]DDE. Binding was found in the hamster adrenal cortex and in assumed cortical cells in the medulla, while the guinea pig adrenal was devoid of binding. This emphasises the species specificity in bioactivation of 3-MeSO2-DDE. The thesis forms a basis for further investigations in the human adrenocortical cell line H295R and provides new knowledge of importance for toxicological risk assessment of 3-MeSO2-DDE.
49.	Merritt, Melissa A., et al. (författare) Nutrient-wide association study of 57 foods/nutrients and epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study 2016 Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 103:1, s. 161-167 Tidskriftsartikel (refereegranskat)abstract Background: Studies of the role of dietary factors in epithelial ovarian cancer (EOC) development have been limited, and no specific dietary factors have been consistently associated with EOC risk.Objective: We used a nutrient-wide association study approach to systematically test the association between dietary factors and invasive EOC risk while accounting for multiple hypothesis testing by using the false discovery rate and evaluated the findings in an independent cohort.Design: We assessed dietary intake amounts of 28 foods/food groups and 29 nutrients estimated by using dietary questionnaires in the EPIC (European Prospective Investigation into Cancer and Nutrition) study (n = 1095 cases). We selected 4 foods/nutrients that were statistically significantly associated with EOC risk when comparing the extreme quartiles of intake in the EPIC study (false discovery rate = 0.43) and evaluated these factors in the NLCS (Netherlands Cohort Study; n = 383 cases). Cox regression models were used to estimate HRs and 95% CIs.Results: None of the 4 dietary factors that were associated with EOC risk in the EPIC study (cholesterol, polyunsaturated and saturated fat, and bananas) were statistically significantly associated with EOC risk in the NLCS; however, in meta-analysis of the EPIC study and the NLCS, we observed a higher risk of EOC with a high than with a low intake of saturated fat (quartile 4 compared with quartile 1; overall HR: 1.21; 95% CI: 1.04, 1.41).Conclusion: In the meta-analysis of both studies, there was a higher risk of EOC with a high than with a low intake of saturated fat.
50.	Messeter, Jörn, 1963-, et al. (författare) Contextualizing mobile IT 2004 Ingår i: Proceedings of Designing Interactive Systems 2004. - : ACM Press. Konferensbidrag (refereegranskat)

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