| 1. |
- Andersson, Lenastina, et al.
(författare)
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Mälsåker Revisited: Museum och Iscensättning. : Kungl Konsthögskolan. Restaureringskonst 2015-2016
- 2016
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Rapport (populärvet., debatt m.m.)abstract
- Rapporten redovisar arbeten från kursen Restaureringskonst på Konsthögskolan som under läsåret 2015-2016 har arbetat med tema Museum och Iscensättning. Hur kulturmiljöer påverkas när de blir museum, hur man restaurerar för museum, hur man bevarar och utvecklar en plats för kunskapsutbyte, bildning och upplevelser. Mälsåkers slott, utanför Mariefred, förvaltat av Statens Fastighetsverk, var studieobjekt för 20 studenter, (yrkesverksamma arkitekter, antikvarier, ingenjörer, konservatorer m fl) där utbildningens olika studiemoment som uppmätning, inventering, dokumentation har tillämpats. Fältarbetet har följts av studier i historik, kulturhistorisk värdering och analyser som gett visioner och gestaltningsförslag på ny verksamhet i slottet. Rapporten presenterar förslagen, med text, skisser, foton och ritningar. Fyra olika typer av museum med varierande grad av åtgärder, förändringar och utveckling av slottet. Restaureringsexperiment redovisas utifrån traditionella och digitala dokumentationsmetoder. Dessutom finns arbeten om barockens ljus, bladguld, brandskydd, pod-radio, kraftstation, engelska parken, dekorationsmålade tak, Gustavianum, Julius Kronbergs ateljé och barockträdgård m m. Förslagen visar att det är möjligt att transformera Mälsåkers barockslott till ett museum av idag med bibehållen historik och synliga tidslager.
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| 2. |
- Anthon, Carl Thomas, et al.
(författare)
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Platelet transfusions in adult ICU patients with thrombocytopenia : A sub-study of the PLOT-ICU inception cohort study
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Platelet transfusions are frequently used in the intensive care unit (ICU), but current practices including used product types, volumes, doses and effects are unknown.STUDY DESIGN AND METHODS: Sub-study of the inception cohort study 'Thrombocytopenia and Platelet Transfusions in the ICU (PLOT-ICU)', including acutely admitted, adult ICU patients with thrombocytopenia (platelet count <150 × 10 9/L). The primary outcome was the number of patients receiving platelet transfusion in ICU by product type. Secondary outcomes included platelet transfusion details, platelet increments, bleeding, other transfusions and mortality. RESULTS: Amongst 504 patients with thrombocytopenia from 43 hospitals in 10 countries in Europe and the United States, 20.8% received 565 platelet transfusions; 61.0% received pooled products, 21.9% received apheresis products and 17.1% received both with a median of 2 (interquartile range 1-4) days from admission to first transfusion. The median volume per transfusion was 253 mL (180-308 mL) and pooled products accounted for 59.1% of transfusions, however, this varied across countries. Most centres (73.8%) used fixed dosing (medians ranging from 2.0 to 3.5 × 10 11 platelets/transfusion) whilst some (mainly in France) used weight-based dosing (ranging from 0.5 to 0.7 × 10 11 platelets per 10 kg body weight). The median platelet count increment for a single prophylactic platelet transfusion was 2 (-1 to 8) × 10 9/L. Outcomes of patients with thrombocytopenia who did and did not receive platelet transfusions varied. CONCLUSIONS: Among acutely admitted, adult ICU patients with thrombocytopenia, 20.8% received platelet transfusions in ICU of whom most received pooled products, but considerable variation was observed in product type, volumes and doses across countries. Prophylactic platelet transfusions were associated with limited increases in platelet counts.
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| 3. |
- Anthon, Carl Thomas, et al.
(författare)
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Thrombocytopenia and platelet transfusions in ICU patients : an international inception cohort study (PLOT-ICU)
- 2023
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Ingår i: Intensive Care Medicine. - 0342-4642. ; 49:11, s. 1327-1338
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Thrombocytopenia (platelet count < 150 × 10 9/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. METHODS: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses.RESULTS: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42).CONCLUSION: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.
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| 4. |
- Dahl, Christina, et al.
(författare)
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Mutual Exclusivity Analysis of Genetic and Epigenetic Drivers in Melanoma Identifies a Link Between p14(ARF) and RAR beta Signaling
- 2013
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Ingår i: Molecular Cancer Research. - 1557-3125. ; 11:10, s. 1166-1178
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Tidskriftsartikel (refereegranskat)abstract
- Melanoma genomes contain thousands of alterations including: mutations, copy number alterations, structural aberrations, and methylation changes. The bulk of this variation is stochastic and functionally neutral, with only a small minority representing "drivers" that contribute to the genesis and maintenance of tumors. Drivers are often directly or inversely correlated across tumors, reflecting the molecular and regulatory signaling pathways in which they operate. Here, a profile of genetic and epigenetic drivers in 110 human melanoma cell lines was generated and searched for non-random distribution patterns. Statistically significant mutual exclusivity was revealed among components of each of the p16(INK4A)-CDK4-RB, RAS-RAF-MEK-ERK and PI3K-AKT signaling pathways. In addition, an inverse correlation was observed between promoter hypermethylation of retinoic acid receptor beta (RARB) and CDKN2A alterations affecting p14(ARF) (P < 0.0001), suggesting a functional link between RAR beta signaling and the melanoma-suppressive activities of p14(ARF). Mechanistically, all-trans retinoic acid (ATRA) treatment increased the expression of p14(ARF) in primary human melanocytes and the steady-state levels of p14(ARF) in these cells were shown to be regulated via RAR beta. Furthermore, the ability of ATRA to induce senescence is reduced in p14(ARF)-depleted melanocytes, and we provide proof-of-concept that ATRA can induce irreversible growth arrest in melanoma cells with an intact RARb-p14(ARF) signaling axis, independent of p16(INK4A) and p53 status. Implications: These data highlight the power of mutual exclusivity analysis of cancer drivers to unravel molecular pathways and establish a previously unrecognized cross-talk between RAR beta and p14(ARF) with potential implications for melanoma treatment.
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| 5. |
- Espenes, J., et al.
(författare)
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Regression-based normative data for the Rey Auditory Verbal Learning Test in Norwegian and Swedish adults aged 49-79 and comparison with published norms
- 2023
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Ingår i: Clinical Neuropsychologist. - : Informa UK Limited. - 1385-4046 .- 1744-4144. ; 37:6, s. 1276-1301
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The Rey Auditory Verbal Learning Test (RAVLT) is a widely used measure of episodic verbal memory. To our knowledge, culturally adapted and demographically adjusted norms for the RAVLT are currently not available for Norwegian and Swedish adults, and imported North American norms are often used. We here develop regression-based norms for Norwegian and Swedish adults and compare our norms to North American norms in an independent sample of cognitively healthy adults. Method: Participants were 244 healthy adults from Norway and Sweden between the aged 49 and 79 years, with between 6 and 24 years of education. Using a multiple multivariate regression-based norming procedure, we estimated effects of age, sex, and years of education on basic and derived RAVLT test scores. The newly developed norms were assessed in an independent comparison group of cognitively healthy adults (n = 145) and compared to recently published North American regression-based norms. Results: Lower age, female sex and more years of education predicted higher performance on the RAVLT. The new norms adequately adjusted for age, education, and sex in the independent comparison group. The American norms corrected for demographics on all RAVLT trials except trials 4, 7, list B, and trials 1-5 total. Test-retest (M = 2.55 years) reliability varied from poor to good. Conclusion: We propose regression-based norms for the RAVLT adjusting for pertinent demographics. The norms may be used for assessment of Norwegian and Swedish adults between the aged of 49 and 79 years, with between 6 and 24 years of education.
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| 6. |
- Gustafsson, Åsa, et al.
(författare)
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Genetic variation influences immune responses in sensitive rats following exposure to TiO2 nanoparticles
- 2014
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Ingår i: Toxicology. - : Elsevier. - 0300-483X .- 1879-3185. ; 326, s. 74-85
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This study examines the immunological responses in rats following inhalation to titanium dioxide nanoparticles (TiO2 NPs), in naïve rats and in rats with induced allergic airway disease. The responses of two different inbred rat strains were compared: the Dark Aguoti (DA), susceptible to chronic inflammatory disorders, and the Brown Norwegian (BN), susceptible to atopic allergic inflammation. Naïve rats were exposed to an aerosol of TiO2 NPs once daily for 10 days. Another subset of rats was sensitized to the allergen ovalbumin (OVA) in order to induce airway inflammation. These sensitized rats were exposed to TiO2 NPs before and during the allergen challenge. Naïve rats exposed to TiO2 NPs developed an increase of neutrophils and lymphocytes in both rat strains. Airway hyperreactivity and production of inflammatory mediators typical of a T helper 1 type immune response were significantly increased, only in DA rats. Sensitization of the rats induced a prominent OVA-specific-IgE and IgG response in the BN rat while DA rats only showed an increased IgG response. Sensitized rats of both strains developed airway eosinophilia following allergen challenge, which declined upon exposure to TiO2 NPs. The level of neutrophils and lymphocytes increased upon exposure to TiO2 NPs in the airways of DA rats but remained unchanged in the airways of BN rats. In conclusion, the responses to TiO2 NPs were strain-dependent, indicating that genetics play a role in both immune and airway reactivity. DA rats were found to be higher responder compared to BN rats, both when it comes to responses in naïve and sensitized rats. The impact of genetically determined factors influencing the inflammatory reactions pinpoints the complexity of assessing health risks associated with nanoparticle exposures.
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| 7. |
- Gustafsson, Åsa, 1975-
(författare)
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Nanomaterials : respiratory and immunological effects following inhalation of engineered nanoparticles
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Nanotechnology is an important and promising field that can lead to improved environment and human health and contribute to a better social and economic development. Materials in nanoscale have unique physiochemical properties which allow for completely new technical applications. Enlarged surface area and properties due to quantum physics are among the properties that distinguish the nanoscale. Nano safety has evolved as a discipline to evaluate the adverse health effects from engineered nanomaterials (ENMs). The prevalence of allergic diseases is increasing in the society. An additional issue is the influence of inherited factors on the health responses to ENMs. The aim of this thesis was to investigate the respiratory, inflammatory, and immunological effects following inhalation of ENMs; both sensitive and genetically susceptible individuals were used. Sensitive individuals refer to individuals with pre-existing respiratory diseases, such as allergic asthma, and genetically susceptible individuals refer to individuals prone to autoimmune and allergic diseases. Methods In vivo models of mice and rats were used. In study I the inflammatory and immune responses following exposure to titanium dioxide nanoparticles (TiO2 NPs) were investigated. The effect of when the TiO2 NP exposure occurs during the development of allergic airway inflammation was investigated in study II, with regards to respiratory, inflammatory, and immune responses. In study III, the influence of the genetics on the respiratory, inflammatory, and immune responses, following TiO2 NP exposure to naïve and sensitive rats was evaluated. In study IV, the inflammatory and immune responses of naïve mice and mice with an allergic airway inflammation were studied in lung fluid and lymph nodes draining the airways following inhalation to hematite NPs (α-Fe2O2).Results Exposure to TiO2 NPs induced a long-lasting lymphocytic response in the airways, indicating a persistent immune stimulation. The dose and timing of TiO2 NP exposure affected the airway response in mice with allergic airway disease. When the mice were exposed to particles and an allergen during the same period, a decline in general health was observed. By comparing different inbred rat strains it was demonstrated that genetically determined factors influence the immune and respiratory responses to TiO2 NP exposure in both naïve and sensitive individuals. Exposure to hematite NPs resulted in different cellular responses: naïve mice had increased numbers of cells while mice with allergic airway inflammation had decreased cell numbers in BALF. Analogous cell responses were also observed in the lung draining lymph nodes.Conclusion Altogether, this thesis emphasises the complexity of assessing health risks associated with nanoparticle exposure and the importance of including sensitive populations when evaluating adverse health effects of ENMs.
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| 8. |
- Gustafsson, Åsa, et al.
(författare)
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Strain differences influence timing and magnitude of both acute and late inflammatory reactions after intratracheal instillation of an alkylating agent in rats
- 2014
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Ingår i: Journal of Applied Toxicology. - : John Wiley & Sons. - 0260-437X .- 1099-1263. ; 34:3, s. 272-280
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Tidskriftsartikel (refereegranskat)abstract
- The acute pulmonary responses after exposure to sulfur and nitrogen mustards are well documented whereas the late pulmonary effects are not. With a novel focus on the immune system this paper investigate whether late phase pulmonary effects developed in rats exposed to the nitrogen mustard melphalan are linked to the acute responses and whether the reactions are genetically regulated. The DA rat strain was used to establish a lung exposure model. Five other inbred rat strains (PVG, PVG.1AV1, LEW, WF and F344) were compared within the model at selected time points. All rat strains displayed a biphasic pattern of leukocyte infiltration in the lungs, dominated by neutrophils 2days after exposure and a second peak dominated by macrophages 29days after exposure. The number of macrophages was higher in the DA rat compared with the other strains. The infiltration of lymphocytes in the lungs varied in both time of appearance and magnitude between strains. The quantity of collagen deposition in the lungs varied between strains at day 90; LEW and WF displayed high collagen content which coincided with an increased level of cytotoxic T cells. LEW further displayed an increased number of T helper cells and natural killer (NK) T cells in the lungs. The results in this study suggest there is a link between the development of lung fibrosis and high cytotoxic cell responses and that there is a genetic influence, as there are variations in acute and late adverse reactions between rat strains in both timing and magnitude.Copyright (c) 2013 John Wiley & Sons, Ltd.
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| 9. |
- Larsson, E, et al.
(författare)
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Corticosteroid treatment of experimental arthritis retards cartilage destruction as determined by histology and serum COMP
- 2004
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1460-2172 .- 1462-0324. ; 43:4, s. 428-434
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To examine if changes in serum cartilage oligomeric matrix protein (COMP) correlate with the development of cartilage damage, as measured by histological grading, in corticosteroid-treated animals with collagen-induced arthritis (CIA). Methods. DA rats with established CIA were treated with corticosteroids (betamethasone, 0.1 mg/kg body weight) or placebo (saline) intraperitoneally once daily after reaching an arthritis score exceeding 1. The treatment continued throughout the study. Arthritis progression was monitored by clinical scoring of paws, serial measurements of serum COMP and fibrinogen, and histological grading of paws. Results. Corticosteroid treatment reduced clinical signs of arthritis compared with placebo (arthritis score reduced, P < 0.01 at day 25). Corticosteroid treatment also reduced fibrinogen levels compared with placebo (P < 0.01). The morphological changes in the joint were less severe in the corticosteroid-treated animals (median cartilage score 4 in the placebo group, 0 in the corticosteroid-treated group; P < 0.01). The levels of COMP remained unchanged during treatment in the corticosteroid-treated arthritic animals, whereas an increase in levels of COMP was observed in rats treated with placebo (P < 0.01). There was a correlation between serum COMP and the extent of cartilage destruction at day 25 after immunization (r=0.77, P < 0.001). Conclusions. Corticosteroids given therapeutically to arthritic rats diminish joint destruction histologically, and stable serum COMP levels reflect this effect.
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| 10. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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