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Sökning: WFRF:(Gustafsson Rolf)

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1.
  • Gustafsson, Margareta, 1952-, et al. (författare)
  • Identifying clinically relevant groups of hip fracture patients at risk of adverse outcomes by using classification tree analysis
  • 2012
  • Ingår i: International Journal of Orthopaedic and Trauma Nursing. - London, United Kingdom : Elsevier. - 1878-1241 .- 1878-1292. ; 17:1, s. 38-47
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To identify groups of hip fracture patients at risk of adverse utcome by investigating interactions between previously reported risk factors.Methods: A consecutive sample of 338 hip fracture patients was included at admission to the orthopaedic department and followed up 4 months later. Outcomes measured were mortality, failure to regain pre-injury mobility and failure to return home. Data were collected about previously reported risk factors for adverse outcomes in those respects.Results: The highest risk of death occured in males living in institutions for the elderly before the fracture (48%). Lowest risk of death had patients admitted from their own home, without malignancy and below 80 years of age (1%). The overall risk of failure to regain pre-injury mobility at the 4 month follow up was 30%. In patients walking independently before the fracture and age above 85 years, the risk increased to 88%. In patients walking with devices before the fracture, the risk of being confined to bed or wheelchair increased from 10% to 20% if the patient was confused. Confusion also increased the risk of relocation from their own home to an institution for the elderly from 19% to 53%.Conclusion: The results of the study can help nurses in making realistic discharge plans based on risk analyses, employing more than just age as risk factor. Using this information nurses can meet the patient’s individual needs in an improved way.
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2.
  • Holmqvist, Rolf, 1948-, et al. (författare)
  • Patients' relationship episodes and therapists' feelings
  • 2002
  • Ingår i: Psychology and Psychotherapy. - : Wiley. - 1476-0835 .- 2044-8341. ; 75:4, s. 393-409
  • Tidskriftsartikel (refereegranskat)abstract
    • The idea that psychotherapists' feelings may reflect some aspect of the content in the patients' material has long been clinically accepted but on the whole poorly systematically studied. The aim of this study was to analyse associations between relationship episodes told by patients at evaluation interviews, and therapists' subsequent feelings towards the patients. In total, 28 psychotherapies with nine psychotherapists were studied. Before therapy started, the clients were interviewed separately by the eventual therapist and a second interviewer and six relationship episodes were written down by the interviewers. During the therapy, the therapists reported their feelings on a 'feeling checklist' after each therapy session. In a first analysis, the relationship episodes were categorized according to the CCRT system. The results indicated only scattered associations between CCRT categories and therapist feelings. The results were, however, difficult to interpret as it was found that the therapists' feeling patterns were quite homogenous for each therapist. Considering this, qualitative analyses were made of six therapies carried out by two therapists. These analyses revealed different but theoretically plausible patterns between the feelings attributed to the persons in the patients' relationship episodes and the therapists' subsequent feelings towards the patients. The results were interpreted as a confirmation of the purported relations between patient relationship episodes and therapist feelings, but also as pointing to the need to develop the understanding of these patterns. It seems particularly important to emphasize the importance of the therapist's own habitual feeling patterns when the impact of the patient's internalized relationship patterns on countertransference reactions is evaluated.
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3.
  • Aftab, Obaid, 1984-, et al. (författare)
  • Detection of cell aggregation and altered cell viability by automated label-free video microscopy : A promising alternative to endpoint viability assays in high throughput screening
  • 2015
  • Ingår i: Journal of Biomolecular Screening. - : Elsevier BV. - 1087-0571 .- 1552-454X. ; 20:3, s. 372-381
  • Tidskriftsartikel (refereegranskat)abstract
    • Automated phase-contrast video microscopy now makes it feasible to monitor a high-throughput (HT) screening experiment in a 384-well microtiter plate format by collecting one time-lapse video per well. Being a very cost-effective and label-free monitoring method, its potential as an alternative to cell viability assays was evaluated. Three simple morphology feature extraction and comparison algorithms were developed and implemented for analysis of differentially time-evolving morphologies (DTEMs) monitored in phase-contrast microscopy videos. The most promising layout, pixel histogram hierarchy comparison (PHHC), was able to detect several compounds that did not induce any significant change in cell viability, but made the cell population appear as spheroidal cell aggregates. According to recent reports, all these compounds seem to be involved in inhibition of platelet-derived growth factor receptor (PDGFR) signaling. Thus, automated quantification of DTEM (AQDTEM) holds strong promise as an alternative or complement to viability assays in HT in vitro screening of chemical compounds.
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4.
  • Aftab, Obaid, 1984-, et al. (författare)
  • Label-free detection and dynamic monitoring of drug-induced intracellular vesicle formation enabled using a 2-dimensional matched filter
  • 2014
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8627 .- 1554-8635. ; 10:1, s. 57-69
  • Tidskriftsartikel (refereegranskat)abstract
    • Analysis of vesicle formation and degradation is a central issue in autophagy research and microscopy imaging is revolutionizing the study of such dynamic events inside living cells. A limiting factor is the need for labeling techniques that are labor intensive, expensive, and not always completely reliable. To enable label-free analyses we introduced a generic computational algorithm, the label-free vesicle detector (LFVD), which relies on a matched filter designed to identify circular vesicles within cells using only phase-contrast microscopy images. First, the usefulness of the LFVD is illustrated by presenting successful detections of autophagy modulating drugs found by analyzing the human colorectal carcinoma cell line HCT116 exposed to each substance among 1266 pharmacologically active compounds. Some top hits were characterized with respect to their activity as autophagy modulators using independent in vitro labeling of acidic organelles, detection of LC3-II protein, and analysis of the autophagic flux. Selected detection results for 2 additional cell lines (DLD1 and RKO) demonstrate the generality of the method. In a second experiment, label-free monitoring of dose-dependent vesicle formation kinetics is demonstrated by recorded detection of vesicles over time at different drug concentrations. In conclusion, label-free detection and dynamic monitoring of vesicle formation during autophagy is enabled using the LFVD approach introduced.
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5.
  • Aftab, Obaid, 1984-, et al. (författare)
  • Label free high throughput screening for apoptosis inducing chemicals using time-lapse microscopy signal processing
  • 2014
  • Ingår i: Apoptosis (London). - : Springer Science and Business Media LLC. - 1360-8185 .- 1573-675X. ; 19:9, s. 1411-1418
  • Tidskriftsartikel (refereegranskat)abstract
    • Label free time-lapse microscopy has opened a new avenue to the study of time evolving events in living cells. When combined with automated image analysis it provides a powerful tool that enables automated large-scale spatiotemporal quantification at the cell population level. Very few attempts, however, have been reported regarding the design of image analysis algorithms dedicated to the detection of apoptotic cells in such time-lapse microscopy images. In particular, none of the reported attempts is based on sufficiently fast signal processing algorithms to enable large-scale detection of apoptosis within hours/days without access to high-end computers. Here we show that it is indeed possible to successfully detect chemically induced apoptosis by applying a two-dimensional linear matched filter tailored to the detection of objects with the typical features of an apoptotic cell in phase-contrast images. First a set of recorded computational detections of apoptosis was validated by comparison with apoptosis specific caspase activity readouts obtained via a fluorescence based assay. Then a large screen encompassing 2,866 drug like compounds was performed using the human colorectal carcinoma cell line HCT116. In addition to many well known inducers (positive controls) the screening resulted in the detection of two compounds here reported for the first time to induce apoptosis.
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6.
  • Aftab, Obaid, 1984-, et al. (författare)
  • Label free quantification of time evolving morphologies using time-lapse video microscopy enables identity control of cell lines and discovery of chemically induced differential activity in iso-genic cell line pairs
  • 2015
  • Ingår i: Chemometrics and Intelligent Laboratory Systems. - 0169-7439 .- 1873-3239. ; 141, s. 24-32
  • Tidskriftsartikel (refereegranskat)abstract
    • Label free time-lapse video microscopy based monitoring of time evolving cell population morphology has potential to offer a simple and cost effective method for identity control of cell lines. Such morphology monitoring also has potential to offer discovery of chemically induced differential changes between pairs of cell lines of interest, for example where one in a pair of cell lines is normal/sensitive and the other malignant/resistant. A new simple algorithm, pixel histogram hierarchy comparison (PHHC), for comparison of time evolving morphologies (TEM) in phase contrast time-lapse microscopy movies was applied to a set of 10 different cell lines and three different iso-genic colon cancer cell line pairs, each pair being genetically identical except for a single mutation. PHHC quantifies differences in morphology by comparing pixel histogram intensities at six different resolutions. Unsupervised clustering and machine learning based classification methods were found to accurately identify cell lines, including their respective iso-genic variants, through time-evolving morphology. Using this experimental setting, drugs with differential activity in iso-genic cell line pairs were likewise identified. Thus, this is a cost effective and expedient alternative to conventional molecular profiling techniques and might be useful as part of the quality control in research incorporating cell line models, e.g. in any cell/tumor biology or toxicology project involving drug/agent differential activity in pairs of cell line models.
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7.
  • Al-Otaibi, M, et al. (författare)
  • Subgingival plaque microbiota in Saudi Arabians after use of miswak chewing stick and toothbrush
  • 2004
  • Ingår i: Journal of Clinical Periodontology. - 0303-6979 .- 1600-051X. ; 31:12, s. 1048-53
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The chewing stick, the miswak, is used in many developing countries as the traditional means for oral hygiene. It is prepared from the roots, twigs and stem of Salvadora persica or other alternative local plants. OBJECTIVES: To compare the effects of the chewing stick miswak (from S. persica) and toothbrush on subgingival plaque microflora among Saudi Arabian individuals. Further, to investigate whether components extracted from S. persica may interfere with the subgingival plaque micro-organisms. MATERIAL AND METHODS: Fifteen healthy Saudi Arabian male volunteers aged 21-36 years were included in a single-blind, randomized cross-over study. The participants were taught how to use each device properly. Plaque sampling for DNA test was performed at the baseline, 1 week after professional tooth cleaning, and after 3 weeks of either miswak or toothbrush use. Identification and quantification of microbial species were performed by the checkerboard method, using whole genomic, digoxigenin-labelled DNA probes. Inhibition zones around miswak were examined on agar plates with Actinobacillus actinomycetemcomitans and the leukotoxicity of this bacterium was analyzed in a bioassay with macrophages+/-extracts of miswak. RESULTS: Miswak and toothbrushing had a similar influence on the levels of the subgingival microbiota. However, A. actinomycetemcomitans was significantly more reduced by miswak (p<0.05) than by toothbrushing. These results were supported by our in vitro results which, indicated that extracts from S. persica might interfere with the growth and leukotoxicity of A. actinomycetemcomitans. CONCLUSIONS: In contrast to toothbrush use, miswak use significantly reduced the amount of A. actinomycetemcomitans in the subgingival plaque.
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9.
  • Andersson, Claes R., et al. (författare)
  • In vitro drug sensitivity-gene expression correlations involve a tissue of origin dependency
  • 2007
  • Ingår i: Journal of chemical information and modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 47:1, s. 239-248
  • Tidskriftsartikel (refereegranskat)abstract
    • A major concern of chemogenomics is to associate drug activity with biological variables. Several reports have clustered cell line drug activity profiles as well as drug activity-gene expression correlation profiles and noted that the resulting groupings differ but still reflect mechanism of action. The present paper shows that these discrepancies can be viewed as a weighting of drug-drug distances, the weights depending on which cell lines the two drugs differ in.
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10.
  • Asayama, Shinichiro, et al. (författare)
  • Three institutional pathways to envision the future of the IPCC
  • 2023
  • Ingår i: Nature Climate Change. - : Nature Portfolio. - 1758-678X .- 1758-6798. ; 13:9, s. 877-880
  • Tidskriftsartikel (refereegranskat)abstract
    • The IPCC has been successful at building its scientific authority, but it will require institutional reform for staying relevant to new and changing political contexts. Exploring a range of alternative future pathways for the IPCC can help guide crucial decisions about redefining its purpose.
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11.
  • Back, Malin, et al. (författare)
  • Reduction in depressive symptoms predicts improvement in eating disorder symptoms in interpersonal psychotherapy : results from a naturalistic study
  • 2020
  • Ingår i: Journal of Eating Disorders. - : BioMed Central. - 2050-2974. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Interpersonal psychotherapy (IPT) can be effective for both Bulimia Nervosa (BN) and co-occurring depression. While changes in symptoms of Eating disorder (ED) and depression have been found to correlate, it is unclear how they interact during treatment and in which order the symptoms decrease.Methods: Thirty-one patients with BN and depressive symptoms received IPT using the manual IPT-BNm in a naturalistic design. The outcome was measured with the Eating Disorder Examination Questionnaire (EDE-Q) and the Montgomery Åsberg Depression Rating Scale (MADRS-S). Symptom improvement at each session was measured with Repeated Evaluation of Eating Disorder Symptoms (REDS) and the Patient Health Questionnaire-9 (PHQ-9).Results: Significant improvements with large effect sizes were found on both ED symptoms and depression. The rates of change were linear for both BN and depression. A strong correlation between reduction of depressive symptoms and ED symptoms was found. Depressive symptom reduction at one session predicted improvement of ED symptoms at the next session.Conclusions: IPT-BNm had an effect on both BN and co-occurring depressive symptoms. The analyses indicated that reduction in depressive symptoms preceded reduction in bulimic symptoms.
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14.
  • Björn, Niclas, 1990-, et al. (författare)
  • Whole-genome sequencing and gene network modules predict gemcitabine/carboplatin-induced myelosuppression in non-small cell lung cancer patients
  • 2020
  • Ingår i: npj Systems Biology and Applications. - : Nature Publishing Group. - 2056-7189. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Gemcitabine/carboplatin chemotherapy commonly induces myelosuppression, including neutropenia, leukopenia, and thrombocytopenia. Predicting patients at risk of these adverse drug reactions (ADRs) and adjusting treatments accordingly is a long-term goal of personalized medicine. This study used whole-genome sequencing (WGS) of blood samples from 96 gemcitabine/carboplatin-treated non-small cell lung cancer (NSCLC) patients and gene network modules for predicting myelosuppression. Association of genetic variants in PLINK found 4594, 5019, and 5066 autosomal SNVs/INDELs with p ≤ 1 × 10−3 for neutropenia, leukopenia, and thrombocytopenia, respectively. Based on the SNVs/INDELs we identified the toxicity module, consisting of 215 unique overlapping genes inferred from MCODE-generated gene network modules of 350, 345, and 313 genes, respectively. These module genes showed enrichment for differentially expressed genes in rat bone marrow, human bone marrow, and human cell lines exposed to carboplatin and gemcitabine (p < 0.05). Then using 80% of the patients as training data, random LASSO reduced the number of SNVs/INDELs in the toxicity module into a feasible prediction model consisting of 62 SNVs/INDELs that accurately predict both the training and the test (remaining 20%) data with high (CTCAE 3–4) and low (CTCAE 0–1) maximal myelosuppressive toxicity completely, with the receiver-operating characteristic (ROC) area under the curve (AUC) of 100%. The present study shows how WGS, gene network modules, and random LASSO can be used to develop a feasible and tested model for predicting myelosuppressive toxicity. Although the proposed model predicts myelosuppression in this study, further evaluation in other studies is required to determine its reproducibility, usability, and clinical effect.
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15.
  • Blömeke, Sigrid, et al. (författare)
  • Conceptual and Methodological Accomplishments of ILSAs, Remaining Criticism and Limitations
  • 2022
  • Ingår i: International Handbook of Comparative Large-Scale Studies in Education: Perspectives, Methods and Findings. - Cham, Switzerland : Springer. - 2197-1951 .- 2197-196X. - 9783030881771 ; , s. 603-655
  • Bokkapitel (refereegranskat)abstract
    • This chapter summarizes conceptual, methodological, and empirical accomplishments and limitations of international large-scale assessments (ILSAs) in education taking into account, among others, the lessons learned from the previous chapters of this handbook. Our intention is to provide a balanced view: On the one hand, we highlight how ILSAs over decades have provided unique contributions to educational research, while on the other hand, we identify limitations of ILSAs and why they may even be harmful to education in some cases.
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16.
  • Boman, Mats, et al. (författare)
  • Corrosion of copper in water free from molecular oxygen
  • 2014
  • Ingår i: Corrosion Engineering, Science and Technology. - 1478-422X .- 1743-2782. ; 49:6, s. 431-434
  • Tidskriftsartikel (refereegranskat)abstract
    • The possibility of copper reacting with O-2-free water has been investigated by analysis of primary corrosion products, as well as by monitoring gas pressure change by time, in long term experiments for up to 6 months in a glove box environment. We establish hydrogen production, but being of the same magnitude irrespective whether copper is present or not. Although low, the hydrogen production rate is considerably larger than what would directly correspond to the amount of analysed copper oxidation products. Our analyses encompass the changes to the surface cleaned copper (99.9999%), the water phase and the Duran glass in contact with the water (ppt quality). We have used very sensitive methods (XPS, AES, ICP-MS, XRF) while keeping contamination risks to a minimum. We conclude that the oxidation rate of copper is very low, yielding only parts of a monolayer of Cu2O after 6 months of exposure at 50 degrees C together with an accompanying very low concentration of copper species (4-5 mu g L-1) in the water phase.
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17.
  • Boström, Magnus, 1972-, et al. (författare)
  • Conditions for Transformative Learning for Sustainable Development : A Theoretical Review and Approach
  • 2018
  • Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 10:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Continued unsustainability and surpassed planetary boundaries require not only scientific and technological advances, but deep and enduring social and cultural changes. The purpose of this article is to contribute a theoretical approach to understand conditions and constraints for societal change towards sustainable development. In order to break with unsustainable norms, habits, practices, and structures, there is a need for learning for transformation, not only adaption. Based on a critical literature review within the field of learning for sustainable development, our approach is a development of the concept of transformative learning, by integrating three additional dimensions—Institutional Structures, Social Practices, and Conflict Perspectives. This approach acknowledges conflicts on macro, meso, and micro levels, as well as structural and cultural constraints. It contends that transformative learning is processual, interactional, long-term, and cumbersome. It takes place within existing institutions and social practices, while also transcending them. The article adopts an interdisciplinary social science perspective that acknowledges the importance of transformative learning in order for communities, organizations, and individuals to be able to deal with global sustainability problems, acknowledging the societal and personal conflicts involved in such transformation.
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18.
  • Boström, Rolf, et al. (författare)
  • Radio and Plasma Wave Observations at Saturn from the Cassini approach and first orbit
  • 2005
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 307, s. 1255-1259
  • Tidskriftsartikel (refereegranskat)abstract
    • We report data from the Cassini radio and plasma wave instrument during the approach and first orbit at Saturn. During the approach, radio emissions from Saturn showed that the radio rotation period is now 10 hours 45 minutes 45 ± 36 seconds, about 6 minutes longer than measured by Voyager in 1980 to 1981. In addition, many intense impulsive radio signals were detected from Saturn lightning during the approach and first orbit. Some of these have been linked to storm systems observed by the Cassini imaging instrument. Within the magnetosphere, whistler-mode auroral hiss emissions were observed near the rings, suggesting that a strong electrodynamic interaction is occurring in or near the rings.
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19.
  • Bäck, Malin, et al. (författare)
  • Interpersonal psychotherapy for eating disorders with co-morbid depression : A pilot study
  • 2017
  • Ingår i: European Journal of Psychotherapy. - : Routledge. - 1364-2537 .- 1469-5901. ; 19:4, s. 378-395
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Patients with eating disorders (ED) often suffer from co-morbid depression, which may complicate the ED treatment. Previous studies have found that ED interventions seem to have limited capacity to reduce depressive symptoms. Several studies of interpersonal psychotherapy (IPT), have found that when patients have been treated for depression, co-morbid symptoms have diminished. As depression and EDs are commonly co-occurring conditions, this pilot study aimed to examine the effect of an IPT treatment for these conditions, with the focus on the depressive symptoms.Method: In this multi-centre study, 16 patients with EDs and co-occurring major depression received 16 weeks of depression-focused IPT.Results: Significant improvements with substantial effect sizes were found for both depression (d = 1.48) and ED (d =.93). Symptom reduction in the two syndromes were strongly correlated (r = .625, p = .004). Patients with a restrictive ED did not improve on either depression or ED symptoms.Conclusion: These findings point to the usefulness of IPT for concurrent depression and ED with a bingeing/purging symptomatology. Working with negative affect and problem-solving related to current interpersonal problems may alleviate general psychological distress among these patients.
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22.
  • Carlson, Rolf, et al. (författare)
  • Modelling hesitation for synthesis of spontaneous speech
  • 2006
  • Ingår i: Proceedings of Speech Prosody 2006. - Dresden. ; , s. 69-72
  • Konferensbidrag (refereegranskat)abstract
    • The current work deals with the modelling of one type of disfluency, hesitations. A perceptual experiment using speech synthesis was designed to evaluate two duration features found to be correlates to hesitation, pause duration and final lengthening. A variation of F0 slope before the hesitation wasalso included. The most important finding is that it is the totalduration increase that is the valid cue rather than the contribution by either factor. In addition, our findings lead us to assume an interaction with syntax. The absence of strong effects of the induced F0 variation was unexpected and we consider several possible explanations for this result.
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  • Educational Policy Evaluation through International Comparative Assessments
  • 2014
  • Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
    • One of the most salient findings from the field of education is that there are huge national differences in student achievement as shown in international comparative studies like PISA and TIMSS. The shockingly large gap between the highest performing countries (mostly in East Asia) and many European countries corresponds to a difference in attainment of two years of schooling. Although this finding has been replicated in several studies, the reasons for and consequences of such differences are currently not well understood.
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26.
  • Edvardsson, Karin, et al. (författare)
  • Dust suppressants efficiency study : in situ measurements of dust generation on gravel roads
  • 2012
  • Ingår i: The international journal of pavement engineering. - : Informa UK Limited. - 1029-8436 .- 1477-268X. ; 13:1, s. 11-31
  • Tidskriftsartikel (refereegranskat)abstract
    • Dust suppressants were applied on fifteen 1 km long test sections at four sites in Sweden during three summer seasons with the objective to compare their relative efficiency and determine minimum application rates in Nordic climate. Dust generation from the test sections was measured both visually and by PM10 measurements. All products except lignosulphonate, sugar and bitumen emulsion showed acceptable efficiency. Chloride solutions were the most efficient. Results indicate the possibility to reduce application rates of chlorides by applying them as solutions instead of solids. The minimum application rate for a chloride solution was estimated at 0.8m(3)/km, which is equivalent to a rate reduction of 50% by weight compared with traditionally applied rates of solid chloride. The results are expected to reduce life cycle costs for gravel roads and contribute to environmental gains by reducing the release of dust into the atmosphere and chemicals into the environment.
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27.
  • Ek, Arne, 1950- (författare)
  • Att konstruera en uppslutning kring den enda vägen : Om folkrörelsers modernisering i skuggan av det östeuropeiska systemskiftet
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis is about some Swedish organizations that are connected to the labour movement and their actions to cope with the new hegemony around market liberalism. After the fall of the Soviet Union in the early 90-ties, the liberal order, meaning market economy and democracy reduced to the election of elites, has become totally domineering both in the western and in the former communist world. Even left wing oriented organizations have adopted their operations and activities accordingly, especially in their internal governing structure. The organizations that I have studied, mainly the Swedish Tenants organization at its local level of Stockholm, developed during the 70-ties and the 80-ties a participatorier member structure. The “Swedish model” of consensus/corporative decision-making and agreement, used by them on the national level for decades, was during that period introduced also on local and regional levels. In the 90-ties these organizations, according to earlier studies, have instead adapted a more costumer-oriented and elite-democratic way of operating and governing. These later changes could be seen as contradicting both the development of the 80-ties and the basic values of those organizations. My questions are therefore how these changes became possible and my aim is to study how the active members have contributed to this development. Using a constructionist theoretical perspective and discourse analysis, I am showing how this potential conflict between a participatory and an elite-democratic model can be reconciled by a discursive construction. The active members have in fact been able see these changes just as a modernization of their organization. From their point-of-view their organization still works in a participatory democratic way. My analysis shows how this ambiguousness and potential paradox became possible thru internal discourses and under influence from the liberal hegemony.
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29.
  • Eriksson, Anna, 1977-, et al. (författare)
  • Towards repositioning of quinacrine for treatment of acute myeloid leukemia - Promising synergies and in vivo effects.
  • 2017
  • Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 63, s. 41-46
  • Tidskriftsartikel (refereegranskat)abstract
    • We previously reported that the anti-malarial drug quinacrine has potential to be repositioned for treatment of acute myeloid leukemia (AML). As a next step towards clinical use, we assessed the efficacy of quinacrine in an AML-PS mouse model and investigated possible synergistic effects when combining quinacrine with nine other antileukemic compounds in two AML cell lines. Furthermore, we explored the in vivo activity of quinacrine in combination with the widely used AML agent cytarabine. The in vivo use of quinacrine (100mg/kg three times per week for two consecutive weeks) significantly suppressed circulating blast cells at days 30/31 and increased the median survival time (MST). The in vitro drug combination analysis yielded promising synergistic interactions when combining quinacrine with cytarabine, azacitidine and geldanamycin. Finally, combining quinacrine with cytarabine in vivo showed a significant decrease in circulating leukemic blast cells and increased MST compared to the effect of either drug used alone, thus supporting the findings from the in vitro combination experiments. Taken together, the repositioning potential of quinacrine for treatment of AML is reinforced by demonstrating significant in vivo activity and promising synergies when quinacrine is combined with different agents, including cytarabine, the hypomethylating agent azacitidine and HSP-90 inhibitor geldanamycin.
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31.
  • Fischer, Walter, et al. (författare)
  • Human alpha-lactalbumin made lethal to tumor cells (HAMLET) kills human glioblastoma cells in brain xenografts by an apoptosis-like mechanism and prolongs survival.
  • 2004
  • Ingår i: Cancer Research. - 1538-7445. ; 64:6, s. 2105-2112
  • Tidskriftsartikel (refereegranskat)abstract
    • Malignant brain tumors present a major therapeutic challenge because no selective or efficient treatment is available. Here, we demonstrate that intratumoral administration of human α-lactalbumin made lethal to tumor cells (HAMLET) prolongs survival in a human glioblastoma (GBM) xenograft model, by selective induction of tumor cell apoptosis. HAMLET is a protein-lipid complex that is formed from α-lactalbumin when the protein changes its tertiary conformation and binds oleic acid as a cofactor. HAMLET induces apoptosis in a wide range of tumor cells in vitro, but the therapeutic effect in vivo has not been examined. In this study, invasively growing human GBM tumors were established in nude rats (Han:rnu/rnu Rowett, n = 20) by transplantation of human GBM biopsy spheroids. After 7 days, HAMLET was administered by intracerebral convection-enhanced delivery for 24 h into the tumor area; and α-lactalbumin, the native, folded variant of the same protein, was used as a control. HAMLET reduced the intracranial tumor volume and delayed the onset of pressure symptoms in the tumor-bearing rats. After 8 weeks, all α-lactalbumin-treated rats had developed pressure symptoms, but the HAMLET-treated rats remained asymptomatic. Magnetic resonance imaging scans revealed large differences in tumor volume (456 versus 63 mm3). HAMLET caused apoptosis in vivo in the tumor but not in adjacent intact brain tissue or in nontransformed human astrocytes, and no toxic side effects were observed. The results identify HAMLET as a new candidate in cancer therapy and suggest that HAMLET should be additionally explored as a novel approach to controlling GBM progression.
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  • Friman, Tomas, et al. (författare)
  • Increased Fibrosis and Interstitial Fluid Pressure in Two Different Types of Syngeneic Murine Carcinoma Grown in Integrin β3-Subunit Deficient Mice
  • 2012
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:3, s. e34082-
  • Tidskriftsartikel (refereegranskat)abstract
    • Stroma properties affect carcinoma physiology and direct malignant cell development. Here we present data showing that alpha(V)beta(3) expressed by stromal cells is involved in the control of interstitial fluid pressure (IFP), extracellular volume (ECV) and collagen scaffold architecture in experimental murine carcinoma. IFP was elevated and ECV lowered in syngeneic CT26 colon and LM3 mammary carcinomas grown in integrin beta(3)-deficient compared to wild-type BALB/ c mice. Integrin beta(3)-deficiency had no effect on carcinoma growth rate or on vascular morphology and function. Analyses by electron microscopy of carcinomas from integrin beta(3)-deficient mice revealed a coarser and denser collagen network compared to carcinomas in wild-type littermates. Collagen fibers were built from heterogeneous and thicker collagen fibrils in carcinomas from integrin beta(3)-deficient mice. The fibrotic extracellular matrix (ECM) did not correlate with increased macrophage infiltration in integrin beta(3)-deficient mice bearing CT26 tumors, indicating that the fibrotic phenotype was not mediated by increased inflammation. In conclusion, we report that integrin beta(3)-deficiency in tumor stroma led to an elevated IFP and lowered ECV that correlated with a more fibrotic ECM, underlining the role of the collagen network for carcinoma physiology.
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34.
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35.
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36.
  • Frost, Britt-Marie, et al. (författare)
  • Increased in vitro cellular drug resistance is related to poor outcome in high-risk childhood acute lymphoblastic leukaemia
  • 2003
  • Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 122, s. 376-
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary. We determined the in vitro cellular drug resistance in 370 children with newly diagnosed acute lymphoblastic leukaemia (ALL). The resistance to each of 10 drugs was measured by the fluorometric microculture cytotoxicity assay (FMCA) and was related to clinical outcome. The median follow-up time was 41 months. Risk-group stratified analyses indicated that in vitro resistance to dexamethasone, doxorubicin and amsacrine were each significantly related to the probability of disease-free survival. In the high-risk (HR) group, increased in vitro resistance to dexamethasone (P = 0·014), etoposide (P = 0·025) and doxorubicin (P = 0·05) was associated with a worse clinical outcome. Combining the results for these drugs provided a drug resistance score with an independent prognostic significance superior to that of any other factor studied, with a relative risk of relapse in the most resistant group 9·8 times that in the most sensitive group (P = 0·007). The results in the intermediate-risk (IR) and standard-risk (SR) groups were less clear cut. In conclusion, our data indicate that in vitro testing of cellular drug resistance can be used to predict the clinical outcome in HR ALL, while the final evaluation of the results in IR and SR patients must await longer follow-up.
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37.
  •  
38.
  • Frost, Britt-Marie, et al. (författare)
  • Translocation t(12;21) is related to in vitro cellular drug sensitivity to doxorubicin and etoposide in childhood acute lymphoblastic leukemia
  • 2004
  • Ingår i: Blood. - Washington : American society of hematology. - 0006-4971 .- 1528-0020. ; 104:8, s. 2452-2457
  • Tidskriftsartikel (refereegranskat)abstract
    • The t(12;21) (p13;q22) translocation resulting in ETV6/RUNX1 (previously named TEL/AML1) gene fusion is present in about 25% of children with precursor B-lineage acute lymphoblastic leukemia (B-ALL). We successfully tested 275 precursor BALL samples from children aged 1 to 17 years to determine the relation between t(12;21) and in vitro cellular drug resistance, measured by the fluorometric microculture cytotoxicity assay (FMCA). Samples from 83 patients (30%) were positive for t(12;21). The ETV6/RUNX1(+) samples were significantly more sensitive than ETV6/RUNX1(-) samples to doxorubicin, etoposide, amsacrine, and dexamethasone, whereas the opposite was true for cytarabine. After matching for unevenly distributed patient characteristics, that is, excluding patients with high hyperdiploidy (> 51 chromosomes), t(g;22), t(1;19), or 11q23 rearrangement, the ETV6/RUNX1(+) samples remained significantly more sensitive to doxorubicin (P = .001) and etoposide (P = .001). For the other drugs tested (amsacrine, cytarabine, dexamethasone, prednisolone, vincristine, 6-thioguanine, and 4-hydroper-oxy-cyclophosphamide), no significant difference in cellular drug sensitivity was found. In conclusion, we found that the presence of the t(12;21) translocation in childhood precursor B-ALL is associated with a high tumor cell sensitivity to doxorubicin and etoposide. High throughput techniques should now be used to elucidate the cellular mechanisms by which ETV6/RUNX1 gene fusion is linked to increased sensitivity to these drugs.
  •  
39.
  • Fryknäs, Mårten, et al. (författare)
  • Phenotype-based screening of mechanistically annotated compounds in combination with gene expression and pathway analysis identifies candidate drug targets in a human squamous carcinoma cell model
  • 2006
  • Ingår i: Journal of Biomolecular Screening. - : Elsevier BV. - 1087-0571 .- 1552-454X. ; 11:5, s. 457-468
  • Tidskriftsartikel (refereegranskat)abstract
    • The squamous cell carcinoma HeLa cell line and an epithelial cell line hTERT-RPE with a nonmalignant phenotype were interrogated for HeLa cell selectivity in response to 1267 annotated compounds representing 56 pharmacological classes. Selective cytotoxic activity was observed for 14 of these compounds dominated by cyclic adenosine monophosphate (cAMP) selective phosphodiesterase (PDE) inhibitors, which tended to span a representation of the chemical descriptor space of the library. The PDE inhibitors induced delayed cell death with features compatible with classical apoptosis. The PDE inhibitors were largely inactive when tested against a cell line panel consisting of hematological and nonsquamous epithelial phenotypes. In a genome-wide DNA microarray analysis, PDE3A and PDE2A were found to be significantly increased in HeLa cells compared to the other cell lines. The pathway analysis software PathwayAssist was subsequently used to extract a list of proteins and small molecules retrieved from Medline abstracts associated with the hit compounds. The resulting list consisted of major parts of the cAMP-protein kinase A pathway linking to ERK, P38, and AKT. This molecular network may provide a basis for further exploitation of novel candidate targets for the treatment of squamous cell carcinoma.
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40.
  • Fryknäs, Mårten, et al. (författare)
  • Screening for phenotype selective activity in multidrug resistant cells identifies a novel tubulin active agent insensitive to common forms of cancer drug resistance
  • 2013
  • Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 13, s. 374-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Drug resistance is a common cause of treatment failure in cancer patients and encompasses a multitude of different mechanisms. The aim of the present study was to identify drugs effective on multidrug resistant cells. Methods: The RPMI 8226 myeloma cell line and its multidrug resistant subline 8226/Dox40 was screened for cytotoxicity in response to 3,000 chemically diverse compounds using a fluorometric cytotoxicity assay (FMCA). Follow-up profiling was subsequently performed using various cellular and biochemical assays. Results: One compound, designated VLX40, demonstrated a higher activity against 8226/Dox40 cells compared to its parental counterpart. VLX40 induced delayed cell death with apoptotic features. Mechanistic exploration was performed using gene expression analysis of drug exposed tumor cells to generate a drug-specific signature. Strong connections to tubulin inhibitors and microtubule cytoskeleton were retrieved. The mechanistic hypothesis of VLX40 acting as a tubulin inhibitor was confirmed by direct measurements of interaction with tubulin polymerization using a biochemical assay and supported by demonstration of G2/M cell cycle arrest. When tested against a broad panel of primary cultures of patient tumor cells (PCPTC) representing different forms of leukemia and solid tumors, VLX40 displayed high activity against both myeloid and lymphoid leukemias in contrast to the reference compound vincristine to which myeloid blast cells are often insensitive. Significant in vivo activity was confirmed in myeloid U-937 cells implanted subcutaneously in mice using the hollow fiber model. Conclusions: The results indicate that VLX40 may be a useful prototype for development of novel tubulin active agents that are insensitive to common mechanisms of cancer drug resistance.
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41.
  • Fryknäs, Mårten, et al. (författare)
  • STAT1 signaling is associated with acquired crossresistance to doxorubicin and radiation in myeloma cell lines
  • 2007
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 120:1, s. 189-195
  • Tidskriftsartikel (refereegranskat)abstract
    • The myeloma cell line RPMI 8226/S and its doxorubicin resistant subline 8226/Dox40 were used as models to explore the potential importance of the STAT1 signaling pathway in drug and radiation resistance. The 40-fold doxorubicin resistant subline 8226/Dox40 was found to be crossresistant to single doses of 4 and 8 Gy of radiation. A genome-wide mRNA expression study comparing the 8226/Dox40 cell line to its parental line was performed to identify the underlying molecular mechanisms. Seventeen of the top 50 overexpressed genes have previously been implicated in the STAT1 signaling pathway. STAT1 was over expressed both at the mRNA and protein level. Moreover, analyses of nuclear extracts showed higher abundance of phosphorylated STAT1 (Tyr 701) in the resistant subline. Preexposure of the crossresistant cells to the STAT1 inhibiting drug fludarabine reduced expression of overexpressed genes and enhanced the effects of both doxorubicin and radiation. These results show that resistance to doxorubicin and radiation is associated with increased STAT1 signaling and can be modulated by fludarabine. The data support further development of therapies combining fludarabine and radiation.
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42.
  •  
43.
  • Gustafsson, A., et al. (författare)
  • Carbohydrate-dependent inhibition of Helicobacter pylori colonization using porcine milk
  • 2006
  • Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 16:1, s. 1-10
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast milk has a well-known anti-microbial effect, which is in part due to the many different carbohydrate structures expressed. This renders it a position as a potential therapeutic for treatment of infection by different pathogens, thus avoiding the drawbacks of many antibiotics. In a previous study, we showed that pigs express the Helicobacter pylori receptors, sialyl Lewis x (Le x) and Le b, on various milk proteins. Here, we investigate the pig breed- and individual-specific expression of these epitopes, as well as the inhibitory capacity of porcine milk on H. pylori binding and colonization. Milk proteins from three different pig breeds were analysed by western blotting using antibodies with known carbohydrate specificity. An adhesion assay was used to investigate the capacity of pig milk to inhibit H. pylori binding to neoglycoproteins carrying Le b and sialyl-di-Le x. alpha1,3/4-fucosyltransferase transgenic FVB/N mice, known to express Le b and sialyl Le x in their gastric epithelium, were colonized by H. pylori and were subsequently treated with Le b- and sialyl Le x-expressing or nonexpressing porcine milk, or water (control) only. The degree of H. pylori colonization in the different treatment groups was quantified. The expression of the Le b and sialyl Le x carbohydrate epitopes on pig milk proteins was breed- and individual specific and correlated to the ability of porcine milk to inhibit H. pylori adhesion in vitro and H. pylori colonization in vivo. Milk from certain pig breeds may have a therapeutic and/or prophylactic effect on H. pylori infection.
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44.
  • Gustafsson, Anders, et al. (författare)
  • Handbok Fuktsäkra utfackningsväggar med hög prefabriceringsgrad enligt den "holländska metoden"
  • 2010
  • Rapport (refereegranskat)abstract
    • The aim of this work was to present a solution of design, manufacture and assemble prefabricated infill walls with good quality. The rapport is based on information from Holland. The aim is that designers, manufacturers and contractors and others must have a working basis for how to build and design infill walls with high prefabrication grade in a efficient and quality controlled process. The report also deals with aspects of the wall function and practical observations that are important to consider.
  •  
45.
  • Gustafsson, Bengt, et al. (författare)
  • Astronomi och rymdvetenskap
  • 2001
  • Ingår i: Vetenskapens framsteg.
  • Bokkapitel (populärvet., debatt m.m.)
  •  
46.
  •  
47.
  • Gustafsson, Gunnar, et al. (författare)
  • The acute response of plasma brain-derived neurotrophic factor as a result of exercise in major depressive disorder.
  • 2009
  • Ingår i: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0165-1781. ; 169:3, s. 244-248
  • Tidskriftsartikel (refereegranskat)abstract
    • Brain-derived neurotrophic factor (BDNF) and other neurotrophins are believed to play an important role in affective disorders. In this study we investigated plasma-BDNF response during an incremental exercise test in 18 patients suffering from moderate major depressive disorder (MDD) and 18 controls. The patients were not treated with antidepressants or neuroleptics. Possible associations between plasma plasma-BDNF levels, dexamethasone suppression test cortisol levels and Montgomery-Asberg Depression Rating Scale (MADRS) scores were also tested. No difference in basal BDNF levels between patients and controls was found. BDNF increased significantly during exercise in both male and female patients as well as in male controls, with no significant differences between the groups. BDNF levels declined after exercise, but after 60 min of rest BDNF levels showed tendencies to increase again in male patients. No correlation between BDNF and cortisol or MADRS scores was found. We conclude that unmedicated patients with moderate depression and normal activity of the hypothalamic-pituitary-adrenal axis do not have a disturbed peripheral BDNF release during exercise. The BDNF increase 60 min after interruption of exercise in male patients might indicate up-regulated BDNF synthesis, but this needs to be further investigated in future studies.
  •  
48.
  • Gustafsson, Jan-Eric, 1949, et al. (författare)
  • Inspections of Swedish schools: A critical reflection on intended effects, causal mechanisms and methods.
  • 2014
  • Ingår i: Education Inquiry. - 2000-4508. ; 5:4, s. 461-479
  • Tidskriftsartikel (refereegranskat)abstract
    • The article outlines a programme theory for the Swedish school inspection. The theory has a format of ‘if . . . then . . . because’, whereby the last term states one or more generative mechanisms behind the reactions to inspection, and the former terms imply what the inspectorate does and which reactions it receives. The assumptions of the theory are tested regarding their precision of definition, consistency and empirical status. No research has as yet confirmed a general positive effect of the Swedish inspection on learning and school development. Programme theory, however, suggests that such effects are mostly context-dependent, and thus will vary between schools and school authorities. A complicating feature of the present inspection is its objectivist ethos, which is at odds with the Swedish tradition of a transactional ethos in inspections.
  •  
49.
  • Gustafsson, John-Eric, et al. (författare)
  • Intet är främmande för en fornvårdare­­
  • 1986
  • Ingår i: Kulturminnesvård. - Stockholm : Riksantikvarieämbetet. - 0346-9077. ; :3-4, s. 35-39
  • Tidskriftsartikel (populärvet., debatt m.m.)
  •  
50.
  • Gustafsson, Jenny, et al. (författare)
  • Var är vi hemma? : Bostadens och det offentliga livets förändrade betydelse
  • 2007
  • Ingår i: I&M. Invandrare & minoriteter. - 1404-6857. ; 34:4-5, s. 15-18
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Människor är både olika och söker umgänge på olika sätt. Skillnader i kultur och behov kräver variation i stadsplaneringen och olika stadsformer. Detta för att främja det spontana, offentliga liv, som behövs för att motverka xenofobin.
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