| 1. |
- Lindahl, Lise M., et al.
(författare)
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STAT5 induces miR-21 expression in cutaneous T cell lymphoma
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:29, s. 45730-45744
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Tidskriftsartikel (refereegranskat)abstract
- In cutaneous T cell lymphomas (CTCL), miR-21 is aberrantly expressed in skin and peripheral blood and displays anti-apoptotic properties in malignant T cells. It is, however, unclear exactly which cells express miR-21 and what mechanisms regulate miR-21. Here, we demonstrate miR-21 expression in situ in both malignant and reactive lymphocytes as well as stromal cells. qRT-PCR analysis of 47 patients with mycosis fungoides (MF) and Sezary Syndrome (SS) confirmed an increased miR- 21 expression that correlated with progressive disease. In cultured malignant T cells miR-21 expression was inhibited by Tofacitinib (CP-690550), a clinical-grade JAK3 inhibitor. Chromatin immunoprecipitation (ChIP) analysis showed direct binding of STAT5 to the miR-21 promoter. Cytokine starvation ex vivo triggered a decrease in miR-21 expression, whereas IL-2 induced an increased miR-21 expression in primary SS T cells and cultured cytokine-dependent SS cells (SeAx). siRNA-mediated depletion of STAT5 inhibited constitutive- and IL-2- induced miR-21 expression in cytokine- independent and dependent T cell lines, respectively. IL-15 and IL-2 were more potent than IL-21 in inducing miR-21 expression in the cytokine-dependent T cells. In conclusion, we provide first evidence that miR-21 is expressed in situ in CTCL skin lesions, induced by IL-2 and IL-15 cytokines, and is regulated by STAT5 in malignant T cells. Thus, our data provide novel evidence for a pathological role of IL-2Rg cytokines in promoting expression of the oncogenic miR-21 in CTCL.
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| 2. |
- Abrahamsson, Marcus, et al.
(författare)
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Analytical Input to Emergency Preparedness at the Municipal Level – a Case Study
- 2007
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Ingår i: Proceedings of Disaster Recovery and Relief: Current & Future Approaches (TIEMS 2007).
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Konferensbidrag (refereegranskat)abstract
- In this paper an approach for employing risk and vulnerability analyses as the basis for emergency preparedness planning is discussed and exemplified using a case study. The study consisted of three connected parts: a broad scope hazard identification and analysis, an assessment of potential assistance needs should any of the hazards materialise and finally a mapping of actors and dependencies. The case study was conducted as a series of workshops, involving key actors from the studied municipality. Some thirty hazard scenarios, originating from five different categories; accidents, epidemics, infrastructure/utilities breakdown/interruption, criminal activity and socially induced scenarios were identified, described and initially evaluated in terms of possible consequences over a range of predefined attributes. In the next step, an analysis of potential assistance needs that may evolve during the identified scenarios was undertaken. Furthermore, an effort was made to identify municipal actors of central importance in the management of potential emergency scenarios, their respective tasks, resources and dependence on service from various technical infrastructures, other actors etc. Examples from the resulting overview of potential emergency scenarios, generated assistance needs and emergency management actors, tasks, resources and dependencies are presented and discussed, alongside with some implications for societal preparedness activities.
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| 3. |
- Bech-Hanssen, Odd, 1956, et al.
(författare)
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Grading right ventricular dysfunction in left ventricular disease using echocardiography: a proof of concept using a novel multiparameter strategy.
- 2021
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Ingår i: ESC heart failure. - : Wiley. - 2055-5822. ; 8:4, s. 3223-3236
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Tidskriftsartikel (refereegranskat)abstract
- Grading right ventricular dysfunction (RVD) in patients with left ventricular (LV) disease has earned little attention. In the present study, we established an echocardiographic RVD score and investigated how increments of the score correspond to RVD at right heart catheterization.We included 95 patients with LV disease consecutively referred for heart transplant or heart failure work-up with catheterization and echocardiography within 48h. The RVD score (5 points) included well-known characteristics of the development from compensated to decompensated right ventricular (RV) function: pulmonary hypertension, reduced RV strain, RV area dilatation, moderate/severe tricuspid regurgitation, and increased right atrial pressure (RAP) by echocardiography. Comparing three groups with increments of RVD score [1 (mild), 2-3 (moderate), and 4-5 (severe)] showed more advanced RVD with increasing RV end-diastolic pressure (P<0.001) and signs of uncoupling to load (reduced ratio between RV and pulmonary artery elastance, P<0.001) and more spherical RV shape (RV area/length, P<0.001). Receiver operating characteristic curve analysis for detection of severe RV (RAP≥10mmHg) showed for the RVD score an area under the curve of 0.88 compared with 0.69, 0.68, and 0.64 for RV strain, tricuspid annular plane systolic excursion, and fractional area change, respectively. A patient with RVD score≥4 had a 6.7-fold increase in likelihood of severe RVD, and no patient with RVD score≤1 had severe RVD.In this proof of concept study, a novel RVD score outperformed the widely used longitudinal parameters regarding grading of RVD severity, with a potential role for refined diagnosis, follow-up, and prognosis assessment in heart failure patients.
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| 4. |
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| 5. |
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| 6. |
- Blumel, Edda, et al.
(författare)
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Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma
- 2019
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Ingår i: Oncoimmunology. - : Taylor & Francis. - 2162-4011 .- 2162-402X. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus is implicated in disease progression in cutaneous T-cell lymphoma (CTCL). Here, we demonstrate that malignant T cell lines derived from CTCL patients as well as primary malignant CD4+ T cells from Sézary syndrome patients are considerably more resistant to alpha-toxin-induced cell death than their non-malignant counterparts. Thus, in a subset of Sézary syndrome patients the ratio between malignant and non-malignant CD4+ T cells increases significantly following exposure to alpha-toxin. Whereas toxin-induced cell death is ADAM10 dependent in healthy CD4+ T cells, resistance to alpha-toxin in malignant T cells involves both downregulation of ADAM10 as well as other resistance mechanisms. In conclusion, we provide first evidence that Staphylococcus aureus derived alpha-toxin can tilt the balance between malignant and non-malignant CD4+ T cells in CTCL patients. Consequently, alpha-toxin may promote disease progression through positive selection of malignant CD4+ T cells, identifying alpha-toxin as a putative drug target in CTCL.
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| 7. |
- Buus, Terkild Brink, et al.
(författare)
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Single-cell heterogeneity in Sézary syndrome
- 2018
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 2:16, s. 2115-2126
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Tidskriftsartikel (refereegranskat)abstract
- Sezary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) with a median life expectancy of less than 4 years. Although initial treatment responses are often good, the vast majority of patients with SS fail to respond to ongoing therapy. We hypothesize that malignant T cells are highly heterogeneous and harbor subpopulations of SS cells that are both sensitive and resistant to treatment. Here, we investigate the presence of single-cell heterogeneity and resistance to histone deacetylase inhibitors (HDACi) within primary malignant T cells from patients with SS. Using single-cell RNA sequencing and flow cytometry, we find that malignant T cells from all investigated patients with SS display a high degree of single-cell heterogeneity at both the mRNA and protein levels. We show that this heterogeneity divides the malignant cells into distinct subpopulations that can be isolated by their expression of different surface antigens. Finally, we show that treatment with HDACi (suberanilohydroxamic acid and romidepsin) selectively eliminates some subpopulations while leaving other subpopulations largely unaffected. In conclusion, we show that patients with SS display a high degree of single-cell heterogeneity within the malignant T-cell population, and that distinct subpopulations of malignant T cells carry HDACi resistance. Our data point to the importance of understanding the heterogeneous nature of malignant SS cells in each individual patient to design combinational and new therapies to counter drug resistance and treatment failure.
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| 8. |
- Fredholm, Angelica, et al.
(författare)
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The practice of thresholds : Autonomy in clinical education explored through variation theory and the threshold concepts framework
- 2020
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Ingår i: Teaching in Higher Education. - : Taylor & Francis. - 1356-2517 .- 1470-1294. ; 25:3, s. 305-320
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Tidskriftsartikel (refereegranskat)abstract
- This paper demonstrates a practical dimension to the discussion about threshold concepts. Threshold concepts have thus far mostly been acknowledged to elucidate learning processes mainly connected to theoretical concepts. By exploring situations that prompted experiences of autonomy and authenticity in clinical learning, findings showed how a practical experience could have the same power to transform thinking and identity as theoretical thresholds and serve as a trigger for transformational learning, therefore making the discussion about ‘practical thresholds' or thresholds in practice possible. The present study explores situations that prompted autonomy and authenticity, and offers context for and substance to these situations by adopting variation theory and the threshold concept framework. In order to learn more about situations that prompt experiences of autonomy and authenticity, and create prerequisites for such experiences, this paper examines how students discern and interpret these situations by analysing them through variation theory and the threshold concept framework.
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| 9. |
- Fredholm, Hanna, et al.
(författare)
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Breast cancer in young women : poor survival despite intensive treatment
- 2009
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Ingår i: PLoS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:11, s. e7695-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Breast cancer is uncommon in young women and correlates with a less favourable prognosis; still it is the most frequent cancer in women under 40, accounting for 30-40% of all incident female cancer. The aim of this study was to study prognosis in young women, quantifying how much stage at diagnosis and management on the one hand, and tumour biology on the other; each contribute to the worse prognosis seen in this age group. METHODOLOGY/PRINCIPAL FINDINGS: In a registry based cohort of women aged 20-69 (n = 22 017) with a primary diagnosis of invasive breast cancer (1992-2005), women aged 20-34 (n = 471), 35-39 (n = 858) and 40-49 (n = 4789) were compared with women aged 50-69 years (n = 15 899). The cumulative 5-year relative survival ratio and the relative excess mortality (RER) were calculated. The cumulative 5-year relative survival ratio was lowest in women aged 20-34. The RER was 2.84 for women aged 20-34 and decreased with increasing age (RER 1.76 and 1.17 for women aged 35-39 and 40-49, respectively). The excess risk was, however, present only in disease stages I and II. For women aged 20-34 with stage I disease RER was 4.63, and 6.70 in the subgroup with tumour size 1-10 mm. The absolute difference in stage I between the youngest and the reference groups amounted to nearly 8%, with a 90% 5-year survival in women aged 20-34. In stages IIa and IIb, the relative excess risk was not as dramatic, but the absolute differences approached 15%. The youngest women with small tumours generally received more aggressive treatment than women in older age groups. CONCLUSIONS: After correction for stage, tumour characteristics and treatment, age remained an independent risk factor for breast cancer death in women <35 years of age. The excess risk for young women was only seen in early stages of disease and was most pronounced in women with small tumours. Young women affected by breast cancer have a high risk of dying compared to their middle-aged counterparts even if diagnosed early and receiving an intense treatment.
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| 10. |
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| 11. |
- Fredholm, Hanna, et al.
(författare)
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Breast cancer in young women and prognosis : How important are proliferation markers?
- 2017
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 84, s. 278-289
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Tidskriftsartikel (refereegranskat)abstract
- Aim:Compared to middle-aged women, young women with breast cancer have a higher risk of systemic disease. We studied expression of proliferation markers in relation to age and subtype and their association with long-term prognosis.Methods:Distant disease-free survival (DDFS) was studied in 504 women aged <40 years and 383 women aged >= 40 years from a population-based cohort. Information on patient characteristics, treatment and follow-up was collected from medical records. Tissue microarrays were produced for analysis of oestrogen receptor, progesterone receptor (PR), Her2, Ki-67 and cyclins.Results: Young women with luminal tumours had significantly higher expression of Ki-67 and cyclins. Proliferation markers were prognostic only within this subtype. Ki-67 was a prognostic indicator only in young women with luminal PR+ tumours. The optimal cut-off for Ki-67 varied by age. High expression of cyclin E1 conferred a better DDFS in women aged <40 years with luminal PR- tumours (hazard ratio [HR] 0.47 [0.24-0.92]). Age < 40 years was an independent risk factor of DDFS exclusively in women with luminal B PR+ tumours (HR 2.35 [1.22-4.50]). Young women with luminal B PR- tumours expressing low cyclin E1 had a six-fold risk of distant disease compared with luminal A ( HR 6.21 [2.17-17.6]).Conclusions:The higher expression of proliferation markers in young women does not have a strong impact on prognosis. Ki-67 is only prognostic in the subgroup of young women with luminal PR tumours. The only cyclin adding prognostic value beyond subtype is cyclin E1. Age is an independent prognostic factor only in women with luminal B PR+ tumours.
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| 12. |
- Fredholm, Hanna, et al.
(författare)
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Long-term outcome in young women with breast cancer : a population-based study
- 2016
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 160:1, s. 131-143
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Tidskriftsartikel (refereegranskat)abstract
- Whether young age at diagnosis of breast cancer is an independent risk factor for death remains controversial, and the question whether young age should be considered in treatment decisions is still to be answered. From a population-based cohort of 22,017 women with breast cancer, all women < 35 years (n = 471) were compared to a random sample of 700 women aged 35-69 years from the same cohort. Information on patient and tumor characteristics, treatment, and follow-up was collected from the medical records. Tissue microarrays were produced for analysis of classical biomarkers. Breast cancer-specific survival (BCSS), distant disease-free survival (DDFS), and locoregional recurrence-free survival (LRFS) by age were compared using women 50-69 years as reference. At 10 years follow-up, women < 35 years and 35-39 years had a worse BCSS [age < 35 years 69 % (HR 2.75, 95 % CI 1.93-3.94), age 35-39 years 76 % (HR 2.33, 95 % CI 1.54-3.52), age 40-49 years 84 % (HR 1.53, 95 % CI 0.97-2.39), and age 50-69 years 89 % (reference)]. The worse BCSS was statistically significant in stages I-IIa and Luminal B tumors. At multivariate analysis age < 35 years and 35-39 years confined a risk in LRFS (HR 2.13, 95 % CI 1.21-3.76 and HR 1.97, 95 % CI 1.06-3.68) but not in DDFS and BCSS. In the subgroup of women < 40 years with luminal tumors stage I-IIa, low age remained an independent risk factor also in DDFS (HR 1.87, 95 % CI 1.03-3.44). Young women have a high risk of systemic disease even when diagnosed in an early stage. The excess risk of relapse is most pronounced in Luminal B tumors, where low age is an independent prognostic factor of DDFS and LRFS.
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| 13. |
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| 14. |
- Fredholm, Kent, 1977-
(författare)
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Eleverna, datorn och språket : Studier av skoldatoriseringens effekter på elevers attityder, skrivstrategier och textproduktion i spanskundervisningen på gymnasiet
- 2015
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Kent Fredholm (2015). Eleverna, datorn och språket: Studier av skoldatoriseringens effekter på elevers attityder, skrivstrategier och textproduktion i spanskundervisningen på gymnasiet. (The Pupils, the Computer and the Language: Studies of the Effects of School Computerisation on Pupils’ Attitudes. Writing Strategies and Written Text Production in Upper Secondary School Spanish Classes.) Stockholm University, Studies in Language Education 12. ISBN 978-91-7649-090-7. Written in Swedish, English and Spanish with abstracts in the three languages and a summary in English.The present work is based upon three studies performed between 2012 and 2014 at the Swedish upper secondary school with pupils studying Spanish as a foreign language. The first study investigates through lesson diaries and an online survey the pupils’ attitudes towards and perceptions of computer use in language learning at large, and specifically of online grammar exercises as compared to paper-based exercises. The participating pupils showed mixed attitudes towards using online exercises for grammar practice, with high demands on websites’ design and user friendliness, as well as for the correctness and reliability of automated corrections. A majority preferred mixed teaching methods (including computer use, teacher-led explanations and the use of paper- and pen-based exercises, especially translation tasks). The major advantage of using computers was considered to be for essay writing and information search.The second study investigates how a group of pupils use online resources when writing essays in Spanish, focussing on their extensive use of online translation services such as Google translate. The writing strategies of these pupils with free access to the Internet are compared to the strategies of another group working without Internet access.The third study examines effects of the use of online translation on the language in the pupils’ essays. The texts written with online translation are compared to texts written without Internet access, but with access to printed dictionaries. Few statistically significant differences can be seen between the two groups. These concern grammatical and lexical complexity and accuracy. The most clear differences regard spelling and article/noun/adjective congruence (with higher degrees of accuracy among the users of online translation), and syntax (with fewer errors in the group writing without online translation). The grammatical complexity was also somewhat higher in the online translation group. As for fluency (text length) and complexity, differences can be correlated to the pupils’ proficiency in Spanish, whereas no such correlation can be seen regarding accuracy.
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| 15. |
- Fredholm, Lars
(författare)
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Emergency Management as Co-ordinated Cognitive Modelling on Different Time-scales
- 1999
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report is a result of the work in projects for The Swedish Rescue Services Agency and for The National Board of Civil Emergency Preparedness. The problem is defined as difficulties in establishing rapid and effective management in major fire-fighting and rescue operations. The analyses result in a view that emergency management can be seen as cognitive modelling. The management work of major operations consists of cognitive modelling on different time scales and co-ordinating such models. The work in one time scale is co-ordinated by cognitive modelling in a higher time scale. The aim of emergency management is to achieve control. A basic condition for effective management is that cognitive modelling functions in the work of each engaged time scale. A hypothesis is formulated based on bad experiences to establish anticipation, total and long-term management: When there are difficulties in establishing rapid and effective management one main reason is that when there on one time scale is a need for co-ordination using mental models in a higher time scale, the cognitive modelling on this higher time scale is delayed in relation to the need on the shorter time scale. Further research in order to study this hypothesis is discussed.
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| 16. |
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| 17. |
- Fredholm, Simon, et al.
(författare)
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SATB1 in Malignant T Cells
- 2018
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Ingår i: Journal of Investigative Dermatology. - : Elsevier. - 0022-202X .- 1523-1747. ; 138:8, s. 1805-1815
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Tidskriftsartikel (refereegranskat)abstract
- Deficient expression of SATB1 hampers thymocyte development and results in inept T-cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides, the most frequent variant of cutaneous T-cell lymphoma. Here, we report on a disease stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. STAT5 inhibited SATB1 expression through induction of microRNA-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32), whereas increased SATB1 expression had the opposite effect, indicating that the microRNA-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5 and its upstream activator JAK3 triggered increased SATB1 expression and a concomitant suppression of IL-5 and IL-9 expression in malignant T cells. In conclusion, we provide a mechanistic link between the proto-oncogenic JAK3/STAT5/microRNA-155 pathway, SATB1, and cytokines linked to CTCL severity and progression, indicating that SATB1 dysregulation is involved in cutaneous T-cell lymphoma pathogenesis.
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| 18. |
- Gustavsson, Eva, 1970, et al.
(författare)
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Min plats i biosfären
- 2019
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- “Min plats i biosfären” är en skrift som presenterar forskningsresultat om vilken roll kulturmiljön och de kulturella ekosystemtjänsterna kulturarv och platsidentitet har för människors välbefinnande och för hållbar landskapsförvaltning inom Biosfärområde Vänerskärgården med Kinnekulle. Resultaten i skriften baseras på forskningsprojektet “Kulturmiljö och kulturarv som en del av hållbar landskapsförvaltning” och har genomförts av forskare vid Göteborgs universitet och Högskolan i Gävle.
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| 19. |
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| 20. |
- Uhr, Christian, et al.
(författare)
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Analysing Emergency Response Systems
- 2008
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Ingår i: Journal of Contingencies and Crisis Management. - : Wiley. - 1468-5973 .- 0966-0879. ; 16:2, s. 80-90
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Tidskriftsartikel (refereegranskat)abstract
- We suggest a method that can be used for analysing an emergency response system. Both the literature and empirical findings indicate that response operations sometimes diverge from existing plans when adapting to an event and its consequences. The method, which aims at achieving a better understanding of emergency response management, adopts a systems perspective using various relationships that exist or develop between personnel belonging to those organizations that are part of the emergency response operation. Results of a study of such an emergency response system are presented and discussed in order to demonstrate how the method can be employed.
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| 21. |
- Uhr, Christian, et al.
(författare)
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Att åstadkomma inriktning och samordning - 7 analyser utifrån hanteringen av skogsbranden i Västmanland 2014
- 2015
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Bok (populärvet., debatt m.m.)abstract
- I antologin får du ta del av sju olika analyser av det utmanande arbetet med att åstadkomma inriktning och samordning av samhällets resurser i samband med skogsbranden. Publikationen är ett utvecklingsbidrag och är tänkt att ge vägledning till förbättrad förmåga att hantera framtidens samhällsstörningar. Bakom texterna står sju olika författare som utgått från ambitionen att publicera ett transparant resonemang där slutsatserna är välgrundade och tillämpliga, såväl ur ett praktiskt som ur ett teoretiskt perspektiv. Arbetet utgår från vetenskaplig metodik och grundas bland annat i ett stort antal intervjuer. Flera av författarna var dessutom närvarande under den akuta hanteringen och kunde på detta sätt samla in värdefull data. Målgruppen för materialet är alla de som på olika sätt är intresserade av utvecklingsfrågor inom området ledning och samverkan.
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