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2.
  • Ahmad, Amais, et al. (författare)
  • IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 4 : Prediction accuracy and software comparisons with improved data and modelling strategies
  • 2020
  • Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 156, s. 50-63
  • Tidskriftsartikel (refereegranskat)abstract
    • Oral drug absorption is a complex process depending on many factors, including the physicochemical properties of the drug, formulation characteristics and their interplay with gastrointestinal physiology and biology. Physiological-based pharmacokinetic (PBPK) models integrate all available information on gastro-intestinal system with drug and formulation data to predict oral drug absorption. The latter together with in vitro-in vivo extrapolation and other preclinical data on drug disposition can be used to predict plasma concentration-time profiles in silico. Despite recent successes of PBPK in many areas of drug development, an improvement in their utility for evaluating oral absorption is much needed. Current status of predictive performance, within the confinement of commonly available in vitro data on drugs and formulations alongside systems information, were tested using 3 PBPK software packages (GI-Sim (ver.4.1), Simcyp® Simulator (ver.15.0.86.0), and GastroPlusTM (ver.9.0.00xx)). This was part of the Innovative Medicines Initiative (IMI) Oral Biopharmaceutics Tools (OrBiTo) project.Fifty eight active pharmaceutical ingredients (APIs) were qualified from the OrBiTo database to be part of the investigation based on a priori set criteria on availability of minimum necessary information to allow modelling exercise. The set entailed over 200 human clinical studies with over 700 study arms. These were simulated using input parameters which had been harmonised by a panel of experts across different software packages prior to conduct of any simulation. Overall prediction performance and software packages comparison were evaluated based on performance indicators (Fold error (FE), Average fold error (AFE) and absolute average fold error (AAFE)) of pharmacokinetic (PK) parameters.On average, PK parameters (Area Under the Concentration-time curve (AUC0-tlast), Maximal concentration (Cmax), half-life (t1/2)) were predicted with AFE values between 1.11 and 1.97. Variability in FEs of these PK parameters was relatively high with AAFE values ranging from 2.08 to 2.74. Around half of the simulations were within the 2-fold error for AUC0-tlast and around 90% of the simulations were within 10-fold error for AUC0-tlast. Oral bioavailability (Foral) predictions, which were limited to 19 APIs having intravenous (i.v.) human data, showed AFE and AAFE of values 1.37 and 1.75 respectively. Across different APIs, AFE of AUC0-tlast predictions were between 0.22 and 22.76 with 70% of the APIs showing an AFE > 1. When compared across different formulations and routes of administration, AUC0-tlast for oral controlled release and i.v. administration were better predicted than that for oral immediate release formulations. Average predictive performance did not clearly differ between software packages but some APIs showed a high level of variability in predictive performance across different software packages. This variability could be related to several factors such as compound specific properties, the quality and availability of information, and errors in scaling from in vitro and preclinical in vivo data to human in vivo behaviour which will be explored further. Results were compared with previous similar exercise when the input data selection was carried by the modeller rather than a panel of experts on each in vitro test. Overall, average predictive performance was increased as reflected in smaller AAFE value of 2.8 as compared to AAFE value of 3.8 in case of previous exercise.
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  • Blomstrand, Johanna, et al. (författare)
  • Pain, hand function, activity performance and apprehensiveness, in patients with surgically treated distal radius fractures
  • 2023
  • Ingår i: Journal of Plastic Surgery and Hand Surgery. - : Medical Journals Sweden AB. - 2000-656X .- 2000-6764. ; 57:1-6, s. 247-252
  • Tidskriftsartikel (refereegranskat)abstract
    • Distal radius fracture (DRF) is a common injury, affecting both function and activity performance. Postoperative rehabilitation is an essential part of the treatment of a surgically treated DRF. The study aims were to assess pain, hand function, activity performance and apprehensiveness and their association, during the first three months after a surgically treated DRF. Eighty-eight patients with a DRF were assessed for pain, hand function, activity performance and apprehensiveness three days and two, six and 12 weeks after surgery. The results indicated that pain, range of motion (ROM), grip strength, apprehensiveness, and activity performance (PRWE) improved significantly between follow-ups (p < .001-.01). Apprehensiveness correlated moderately with activity performance on all visits (0.40-0.47, p < .01), which implies a correlation between the variables, but the regression model showed that the differences in the PRWE at twelve weeks cannot be explained by the differences in apprehensiveness or range of motion at cast removal. At 12 weeks, the study participants had regained almost 70% of their grip strength and 74-96% of the ROM of the uninjured hand. The study shows that, during the study period, the participants improved in both pain, hand function and activity performance, and indicates that a simple question on apprehensiveness in terms of using the injured hand in daily life could be an important factor in distal radius fracture rehabilitation.
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  • Carlsson, Lena M S, 1957, et al. (författare)
  • Long-term incidence of serious fall-related injuries after bariatric surgery in Swedish obese subjects.
  • 2019
  • Ingår i: International journal of obesity (2005). - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 43:4, s. 933-937
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity increases risk of falling, but the effect of bariatric surgery on fall-related injuries is unknown. The aim of this study was therefore to study the association between bariatric surgery and long-term incidence of fall-related injuries in the prospective, controlled Swedish Obese Subjects study. At inclusion, body mass index was≥34kg/m2 in men and ≥38kg/m2 in women. The surgery per-protocol group (n=2007) underwent gastric bypass (n=266), banding (n=376), or vertical banded gastroplasty (n=1365), and controls (n=2040) received usual care. At the time of analysis (31 December 2013), median follow-up was 19 years (maximal 26 years). Fall-related injuries requiring hospital treatment were captured using data from the Swedish National Patient Register. During follow-up, there were 617 first-time fall-related injuries in the surgery group and 513 in the control group (adjusted hazard ratio 1.21, 95% CI, 1.07-1.36; P=0.002). The incidence differed between treatment groups (P<0.001, log-rank test) and was higher after gastric bypass than after usual care, banding and vertical banded gastroplasty (adjusted hazard ratio 0.50-0.52, P<0.001 for all three comparisons). In conclusion, gastric bypass surgery was associated with increased risk of serious fall-related injury requiring hospital treatment.
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  • Darwich, Adam S., et al. (författare)
  • IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 3 : Identifying gaps in system parameters by analysing In Silico performance across different compound classes
  • 2017
  • Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 96, s. 626-642
  • Tidskriftsartikel (refereegranskat)abstract
    • Three Physiologically Based Pharmacokinetic software packages (GI-Sim, Simcyp (R) Simulator, and GastroPlus (TM)) were evaluated as part of the Innovative Medicine Initiative Oral Biopharmaceutics Tools project (OrBiTo) during a blinded "bottom-up" anticipation of human pharmacokinetics. After data analysis of the predicted vs. measured pharmacokinetics parameters, it was found that oral bioavailability (F-oral) was underpredicted for compounds with low permeability, suggesting improper estimates of intestinal surface area, colonic absorption and/or lack of intestinal transporter information. Foralwas also underpredicted for acidic compounds, suggesting overestimation of impact of ionisation on permeation, lack of information on intestinal transporters, or underestimation of solubilisation of weak acids due to less than optimal intestinal model pH settings or underestimation of bile micelle contribution. F-oral was overpredicted for weak bases, suggesting inadequate models for precipitation or lack of in vitro precipitation information to build informed models. Relative bioavailability was underpredicted for both high logP compounds as well as poorly water-soluble compounds, suggesting inadequate models for solubility/dissolution, underperforming bile enhancement models and/or lack of biorelevant solubility measurements. These results indicate areas for improvement in model software, modelling approaches, and generation of applicable input data. However, caution is required when interpreting the impact of drug-specific properties in this exercise, as the availability of input parameters was heterogeneous and highly variable, and the modellers generally used the data "as is" in this blinded bottom-up prediction approach.
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  • Destouni, Georgia, et al. (författare)
  • Hydro-Biogeochemical and Environmental-Management Functions of Wetland Networks in Landscapes
  • 2012
  • Ingår i: 9th INTECOL International Wetlands Conference, Wetlands in a Complex World. ; , s. 915-
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • A main application goal of ecohydrological science is to amplify opportunities of achieving water quality improvements, biodiversity enhancements and sustainable development, by improved understanding and use of ecosystem properties as a management tool. This paper draws on and synthesizes main result implications for the function and possible enhanced use of wetland networks in the landscape as such a tool, from a series of hydro-biogeochemical and environmental economics studies of nutrient/pollutant loading and abatement in different Swedish hydrological catchments. Results show large potential of wetland networks to reduce the cost of abating nutrient and metal loads within and from hydrological catchments, and emphasize some main research questions for further investigations of actual possibilities to realize this potential. The questions regard in particular the ability of wetland networks to extend the travel times and reduce the uncertainty of hydrological nutrient/pollutant transport through catchments.The paper further presents and discusses some main joint conclusions of the participants in a recently held International Workshop on Ecohydrology and Integrated Water Resource Management (1) at the Navarino Environmental Observatory in Messinia, Greece (2), regarding essential goals for collaborative international efforts in wetland network research. The goals include to investigate on different spatiotemporal scales and in different world regions: a) the dynamics of natural and managed wetland networks across a gradient of different climate, human disturbance, energy and organization conditions; b) the reciprocal interactions between wetland networks and associated hydrological catchments; c) how climate change and different human activities in the wetland network catchments influence these interactions (in b) and generally the ecohydrology of individual wetlands and the whole wetland networks; and d) the ecosystem services provided by networks of wetlands.
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  • Hellsmark, Hans, 1974, et al. (författare)
  • Teknologiska innovationssystem inom energiområdet: En praktisk vägledning till identifiering av systemsvagheter som motiverar särskilda politiska åtaganden
  • 2014
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Syftet med denna rapport är att illustrera hur ett praktiskt inriktat ramverk, tekno- logiska innovationssystem (TIS), kan användas av analytiker och beslutsfattare vid departement och myndigheter för att analysera strategiskt viktiga teknikområden ?????????????????????????????????????????????????????????????????????????????I rapporten analyseras fem TIS centrerade kring havsbaserad vindkraft, marin energi, ????????????????????????????????????????????????????????????????????????????????????? systemsvagheter som bromsar områdets vidare utveckling, vilka som kan åtgärdas av systemets aktörer och vilka som motiverar särskilda politiska åtaganden. Rapporten utgör därmed ett underlag för att formulera åtgärder för att åstadkomma ökad innova- tion, teknikspridning och industrialisering inom ovan nämnda teknikområden.Studien har även möjliggjort en jämförande analys av likheter och skillnader ???????????????????????????????????????????????????????????????????????????????? ?????????????????????????????????????????????????????????????????????????????????????? mellan områdena – de är starka respektive svaga av olika orsaker. Detta visar att ???????????????????????????????????????????????????????????????????????Samtidigt har områdena gemensamma drag. Systemets aktörer, där även politiska ???????????????????????????????????????????????????????????????????????????????????? ?????????????????????????????????????????????????????????????????????????????- skapsnätverk. Men de har varit sämre på att skapa tidiga nischmarknader som ger utrymme för fortsatt lärande och kostnadsreduktion. Sådana nischer kan ibland skapas av marknadens aktörer, men ofta krävs politiska styrmedel. De behövs för att investeringar i kunskapsutveckling ska kunna nyttiggöras och för att en bred industriell utveckling inom nya områden skall göras möjlig i Sverige.Vidare presenteras lärdomar kring vad en aktiv teknikpolitik innebär. Två huvud- ??????????????????????????????????????????????????????????????????????????????- hällsbygget och därför bör vara ett politikområde bland många samt att den skarpa ??????????????????????????????????????????????????????????????????????????????- ?????????????????????????????????????????????????????????????????????????????????? ?????????????????????????????????????????????????????????????????????????????????? olika faser av innovationssystemets utveckling.För att lyckas med en aktiv teknikpolitik behövs en hög grad av koordinering ??????????????????????????????????????????????????????????????????????? teknikområden så att ”rätt” typ av åtgärder kan sättas in vid ”rätt” tidpunkt av ”rätt” aktör. TIS-ramverket lyfts här fram som en metod för att skapa ett sådant underlag. Slutligen presenteras en metod för projektbedömningar som syftar till att stötta handläggare i utvärderingar av projekt inom nya teknikområden.Rapporten i sin helhet riktar sig särskilt till beslutsfattare och handläggare vid myndigheter, departement och politiker, men även andra organisationer och indi- vider med intresse av att högt ställda klimatmål ska kunna nås samtidigt som en positiv näringslivsutveckling möjliggörs.
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  • Hellsten, Sofie, et al. (författare)
  • Effekter av stormen Gudrun på kväveutlakning från skogsmark
  • 2014
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • I denna rapport utvärderas effekter av stormen Gudrun på 35 ytor inom Krondroppsnätet, framförallt med avseende på kväveutlakningen från skogsmark efter en storm. Resultaten visade på ett tydligt samband mellan stormskadornas omfattning och nitrathalterna i markvattnet, med högre nitrathalter i de ytor som skadades mest. Effekten varierade dock inom samma skadeklass, vilket beror på andra faktorer som till exempel markvegetationen, kvävenedfallet, markvattnets surhetsgrad och beståndets ålder. Uppskalning av resultatet visade att den totala kvävebruttobelastningen till Östersjön och Västerhavet från skogsmark kan öka med ca 8 % till följd av en storm av Gudruns storlek.
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  • Hellsten, Sofie, et al. (författare)
  • Increased concentrations of nitrate in forest soil water after windthrow in southern Sweden
  • 2015
  • Ingår i: Forest Ecology and Management. - : Elsevier BV. - 1872-7042 .- 0378-1127. ; 356, s. 234-242
  • Tidskriftsartikel (refereegranskat)abstract
    • In January 2005, south-west Sweden was hit by a severe storm that caused large damage to the forests through massive windthrow. The aim of this study was to assess the effect of this windthrow on nitrate concentrations in the soil water below the root zone on 33 forest monitoring plots within the Swedish Throughfall Monitoring Network (SWETHRO). These sites were damaged to different extents by the storm. The analysis showed increased levels of nitrate concentrations in the soil water as a consequence of storm damaged forest. The present study concerned forest ecosystems with relatively low levels of nitrogen deposition, as compared with forests analysed in previous studies. The maximum soil water nitrate concentrations occurred 1-4 years after the storm. After 5-6 years, the concentrations were back at the same levels as before the storm event. It was not possible to demonstrate a significant correlation between increased nitrate concentrations in the soil water after the storm and the level of nitrogen deposition at the site. The potential impact on ground- and surface waters due to elevated nitrate concentrations in soil water after storm events is discussed. (C) 2015 Elsevier B.V. All rights reserved.
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14.
  • Karlsson, Johanna, et al. (författare)
  • Att lyfta språket och ämneskunskaperna med hjälp av stöttning (ämnesspecifik text: hem- och konsumentkunskap)
  • 2018
  • Annan publikation (populärvet., debatt m.m.)abstract
    • För att kunna nå målen i ämnet hem- och konsumentkunskap krävs det att eleverna kan klara av uppgifter med hög kognitiv svårighetsgrad. För läraren är stöttning, både i planerad och i tillfällig form, ett viktigt verktyg för att hjälpa eleverna att nå målen. Denna stöttning kan finnas i form av exempelvis rikliga tillfällen till interaktion, tydlig information kring arbetsmoment, samarbete över ämnesgränserna och med studiehandledare samt skolord och ämnesspecifika ord och begrepp som introduceras i rätt sammanhang.
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  • Karlsson, Johanna, et al. (författare)
  • Läsförståelse i alla ämnen (ämnesspecifik text: hem- och konsumentkunskap)
  • 2018
  • Annan publikation (populärvet., debatt m.m.)abstract
    • Att läsa och följa recept är en vanligt förekommande aktivitet inom ämnet hem- och konsumentkunskap. Denna texttyp ställer höga krav på läsfärdigheten hos elever och innebär en extra utmaning för nyanlända elever. Exempel på stöttning som kan ge nyanlända elever möjlighet till parallell språk- och kunskapsutveckling är att arbeta med aktiviteter före, under och efter läsning, att låta eleverna ta hjälp av sitt starkaste språk och att ha ett löpande ämnesöverskridande samarbete
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  • Margolskee, Alison, et al. (författare)
  • IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 2 : An introduction to the simulation exercise and overview of results
  • 2017
  • Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 96, s. 610-625
  • Tidskriftsartikel (refereegranskat)abstract
    • Orally administered drugs are subject to a number of barriers impacting bioavailability (F-oral), causing challenges during drug and formulation development. Physiologically-based pharmacokinetic (PBPK) modelling can help during drug and formulation development by providing quantitative predictions through a systems approach. The performance of three available PBPK software packages (GI-Sim, Simcyp (R), and GastroPlus (TM)) were evaluated by comparing simulated and observed pharmacokinetic (PK) parameters. Since the availability of input parameters was heterogeneous and highly variable, caution is required when interpreting the results of this exercise. Additionally, this prospective simulation exercise may not be representative of prospective modelling in industry, as API information was limited to sparse details. 43 active pharmaceutical ingredients (APIs) from the OrBiTo database were selected for the exercise. Over 4000 simulation output files were generated, representing over 2550 study arm-institution-software combinations and approximately 600 human clinical study arms simulated with overlap. 84% of the simulated study arms represented administration of immediate release formulations, 11% prolonged or delayed release, and 5% intravenous (i.v.). Higher percentages of i.v. predicted area under the curve (AUC) were within two-fold of observed (52.9%) compared to per oral (p.o.) (37.2%), however, F-oral and relative AUC (F-rel) between p.o. formulations and solutions were generally well predicted (64.7% and 75.0%). Predictive performance declined progressing from i.v. to solution and immediate release tablet, indicating the compounding error with each layer of complexity. Overall performance was comparable to previous large-scale evaluations. A general overprediction of AUC was observed with average fold error (AFE) of 1.56 over all simulations. AFE ranged from 0.0361 to 64.0 across the 43 APIs, with 25 showing overpredictions. Discrepancies between software packages were observed for a few APIs, the largest being 606, 171, and 81.7-fold differences in AFE between SimCYP and GI-Sim, however average performance was relatively consistent across the three software platforms.
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  • Mattsson, Johanna Sofia Margareta, 1985-, et al. (författare)
  • Inconsistent results in the analysis of ALK rearrangements in non-small cell lung cancer
  • 2016
  • Ingår i: BMC Cancer. - London, United Kingdom : Springer Science and Business Media LLC. - 1471-2407. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Identification of targetable EML4-ALK fusion proteins has revolutionized the treatment of a minor subgroup of non-small cell lung cancer (NSCLC) patients. Although fluorescence in situ hybridization (FISH) is regarded as the gold standard for detection of ALK rearrangements, ALK immunohistochemistry (IHC) is often used as screening tool in clinical practice. In order to unbiasedly analyze the diagnostic impact of such a screening strategy, we compared ALK IHC with ALK FISH in three large representative Swedish NSCLC cohorts incorporating clinical parameters and gene expression data.Methods: ALK rearrangements were detected using FISH on tissue microarrays (TMAs), including tissue from 851 NSCLC patients. In parallel, ALK protein expression was detected using IHC, applying the antibody clone D5F3 with two different protocols (the FDA approved Ventana CDx assay and our in house Dako IHC protocol). Gene expression microarray data (Affymetrix) was available for 194 patients.Results: ALK rearrangements were detected in 1.7% in the complete cohort and 2.0% in the non-squamous cell carcinoma subgroup. ALK protein expression was observed in 1.9% and 1.5% when applying the Ventana assay or the in house Dako protocol, respectively. The specificity and accuracy of IHC was high (>99%), while the sensitivity was between 69% (Ventana) and 62% (in house Dako protocol). Furthermore, only 67% of the ALK IHC positive cases were positive in both IHC assays. Gene expression analysis revealed that 6/194 (3%) tumors showed high ALK gene expression (≥6AU) and of them only three were positive by either FISH or IHC.Conclusion: The overall frequency of ALK rearrangements based on FISH was lower than previously reported. The sensitivity of both IHC assays was low, and the concordance between the FISH and the IHC assays poor, questioning current strategies to screen with IHC prior to FISH or completely replace FISH by IHC.
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  • Mattsson, Johanna Sofia Margareta, 1985-, et al. (författare)
  • Prognostic impact of COX-2 in non-small cell lung cancer : a comprehensive compartment-specific evaluation of tumor and stromal cell expression
  • 2015
  • Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 356:2, s. 837-845
  • Tidskriftsartikel (refereegranskat)abstract
    • Cyclooxygenase-2 (COX-2) is an enzyme that has been extensively investigated as a prognostic marker in cancer. In non-small cell lung cancer (NSCLC) previous results regarding the prognostic impact of COX-2 expression are inconsistent. Therefore we evaluated the association between transcript levels and overall survival in nine publicly available gene expression data sets (total n = 1337) and determined in situ compartment-specific tumor and stromal cell protein expression in two independent cohorts (n = 616). Gene expression did not show any correlation with clinical parameters or with overall survival. Protein expression in tumor and stromal cells did not correlate with any clinical parameter or with overall survival in one of the analyzed cohorts, while a significant association of high stromal expression with longer survival was observed in both univariate and multivariate analysis in the other cohort. Stromal expression of COX-2 has not been separately evaluated in NSCLC previously and may be a subject of further investigation, whereas the presented findings from this comprehensive compartment specific evaluation clearly reject the hypothesis of COX-2 tumor cell expression having a prognostic value in NSCLC. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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  • Nordén, J., et al. (författare)
  • Nutrition impact symptoms and body composition in patients with COPD
  • 2015
  • Ingår i: European Journal of Clinical Nutrition. - : Nature Publishing Group. - 0954-3007 .- 1476-5640. ; 69:2, s. 256-261
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Objectives:Anorexia or lack of appetite is common in chronic obstructive pulmonary disease (COPD) and may be caused or augmented by several symptoms affecting appetite and eating. We aimed to investigate and quantify the extent of nutrition impact symptoms (NIS) in patients with COPD and to explore relationships between NIS and fat-free mass depletion.Subjects/Methods:The results in this cross-sectional study are based on 169 COPD patients (62% female subjects). Body composition was assessed using bioelectrical impedance spectroscopy and the patients reported NIS by two newly developed questionnaires: the Eating Symptoms Questionnaire (ESQ) and the Disease-Related Appetite Questionnaire (DRAQ).Results:Symptoms with the highest prevalence were dry mouth (71%), stomach ache (39%), pain or aches affecting appetite (36%) and constipation (35%). Problems with diarrhoea and feeling affected by smells were more severe among women compared with men (P<0.05). Thirty-six percent of the patients were depleted (fat-free mass index (FFMI) <15 kg/m(2) for women and FFMI<16 kg/m(2) for men). Depleted patients had more NIS (P<0.05) and also rated appetite and taste of food as worse compared with non-depleted patients (P<0.05).Conclusions:NIS are common in patients with COPD, and depleted patients have more severe symptoms. To investigate how these symptoms are best prevented and/or managed and whether NIS prevention/treatment can affect development of malnutrition in patients with COPD is a challenge for the future.
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  • Steinz, Maarten M, et al. (författare)
  • Oxidative hotspots on actin promote skeletal muscle weakness in rheumatoid arthritis
  • 2019
  • Ingår i: JCI Insight. - : American Society for Clinical Investigation (ASCI). - 2379-3708 .- 2324-7703 .- 2325-4556. ; 4:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Skeletal muscle weakness in patients suffering from rheumatoid arthritis (RA) adds to their impaired working abilities and reduced quality of life. However, little molecular insight is available on muscle weakness associated with RA. Oxidative stress has been implicated in the disease pathogenesis of RA. Here, we show that oxidative posttranslational modifications of the contractile machinery targeted to actin result in impaired actin polymerization and reduced force production. Using mass spectrometry, we identified the actin residues targeted by oxidative 3-nitrotyrosine (3-NT) or malondialdehyde (MDA) adduct modifications in weakened skeletal muscle from mice with arthritis and patients afflicted by RA. The residues were primarily located in 3 distinct regions positioned at matching surface areas of the skeletal muscle actin molecule from arthritic mice and patients with RA. Moreover, molecular dynamics simulations revealed that these areas, here coined "hotspots," are important for the stability of the actin molecule and its capacity to generate filaments and interact with myosin. Together, these data demonstrate how oxidative modifications on actin promote muscle weakness in RA patients and may provide novel leads for targeted therapeutic treatment to improve muscle function.
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  • Tengblad, Jessica, et al. (författare)
  • "I am Here"-The Importance of Caring Touch in Intensive Care. A Qualitative Observation and Interview Study
  • 2023
  • Ingår i: Journal of Holistic Nursing. - : Sage Publications. - 0898-0101 .- 1552-5724.
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The purpose of the study was to illuminate the experience of caring touch in intensive care from the perspectives of patients, next-of-kin, and healthcare professionals. Design and Method: This study was explorative, and data were collected through qualitative observations (n = 9) with subsequent interviews (n = 27) at two general intensive care units. An inductive approach was embraced to be open-minded to the participants' experiences. Findings: The results are presented in one generic category-caring touch creates presence-which generated five subcategories: to touch and be touched with respect, touch as guidance and communication, touch causes suffering, touch creates compassion, and touch creates security. Conclusion: When the ability to communicate with words is lost, it is body language that reveals what a person is trying to express. Nurses create a way of being present with the patients by touching them, to communicate I am here for you. Caring touch is a tool to show compassion and respect and to protect the integrity of the lived body. The caring touch is soothing and comforting for the patient and next-of-kin and creates security. It also helps to awaken the motivation to get healthy, which is needed in an environment that is foreign.
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  • Ahlgren, Serina, et al. (författare)
  • Review of methodological choices in LCA of biorefinery systems - key issues and recommendations
  • 2015
  • Ingår i: Biofuels, Bioproducts and Biorefining. - : Wiley. - 1932-1031 .- 1932-104X. ; 9:5, s. 606-619
  • Forskningsöversikt (refereegranskat)abstract
    • The current trend in biomass conversion technologies is toward more efficient utilization of biomass feedstock in multiproduct biorefineries. Many life-cycle assessment (LCA) studies of biorefinery systems have been performed but differ in how they use the LCA methodology. Based on a review of existing LCA standards and guidelines, this paper provides recommendations on how to handle key methodological issues when performing LCA studies of biorefinery systems. Six key issues were identified: (i) goal definition, (ii) functional unit, (iii) allocation of biorefinery outputs, (iv) allocation of biomass feedstock, (v) land use, and (vi) biogenic carbon and timing of emissions. Many of the standards and guidelines reviewed here provide only general methodological recommendations. Some make more specific methodological recommendations, but these often differ between standards. In this paper we present some clarifications (e.g. examples of research questions and suitable functional units) and methodological recommendations (e.g. on allocation).
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27.
  • Alexeyev, Oleg, et al. (författare)
  • Association between the presence of bacterial 16S RNA in prostate specimens taken during transurethral resection of prostate and subsequent risk of prostate cancer (Sweden)
  • 2006
  • Ingår i: Cancer Causes and Control. - Dordrecht : Kluwer Academic Publishers. - 0957-5243 .- 1573-7225. ; 17:9, s. 1127-1133
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To study bacterial 16S RNA in archival prostate samples from 352 patients with benign prostate hyperplasia (BPH) and evaluate whether the presence of bacterial DNA was different in those who later developed prostate cancer (n = 171) and in the matched controls that did not progress to cancer (n = 181).Methods: 16S DNA PCR followed by cloning and sequencing the positive samples.Results: In 96/352 (27%) of the prostate tissue specimens 16S RNA were detected. Sequence analysis revealed Propionibacterium acnes as the predominant microorganism (23% of 16S RNA positive patients). The second most frequent isolate—Escherichia coli was found in 12 (12%) patients. The other isolates included Pseudomonas sp. (3 patients), Actinomyces sp. (2), Streptococcus mutans (1), Corynebacterium sp. (2),Nocardioides sp. (1), Rhodococcus sp. (1) Veillonella sp. (2). In P. acnes positive samples 62% exhibited severe histological inflammation versus 50% in the bacteria-negative group (p = 0.602). The presence of P. acnes in the prostate was associated with prostate cancer development (OR 2.17, 95% CI 0.77–6.95).Conclusions: This study has revealed P. acnes as the most common bacteria in the prostate in BPH. Further studies are needed to clarify its role in contributing to the development of prostatic inflammation and prostate cancer.
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28.
  • Andersson, Anders, et al. (författare)
  • A transcriptional timetable of autumn senescence
  • 2004
  • Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 5:4, s. R24-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background We have developed genomic tools to allow the genus Populus (aspens and cottonwoods) to be exploited as a full-featured model for investigating fundamental aspects of tree biology. We have undertaken large-scale expressed sequence tag (EST) sequencing programs and created Populus microarrays with significant gene coverage. One of the important aspects of plant biology that cannot be studied in annual plants is the gene activity involved in the induction of autumn leaf senescence. Results On the basis of 36,354 Populus ESTs, obtained from seven cDNA libraries, we have created a DNA microarray consisting of 13,490 clones, spotted in duplicate. Of these clones, 12,376 (92%) were confirmed by resequencing and all sequences were annotated and functionally classified. Here we have used the microarray to study transcript abundance in leaves of a free-growing aspen tree (Populus tremula) in northern Sweden during natural autumn senescence. Of the 13,490 spotted clones, 3,792 represented genes with significant expression in all leaf samples from the seven studied dates. Conclusions We observed a major shift in gene expression, coinciding with massive chlorophyll degradation, that reflected a shift from photosynthetic competence to energy generation by mitochondrial respiration, oxidation of fatty acids and nutrient mobilization. Autumn senescence had much in common with senescence in annual plants; for example many proteases were induced. We also found evidence for increased transcriptional activity before the appearance of visible signs of senescence, presumably preparing the leaf for degradation of its components.
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29.
  • Andersson, Johanna, et al. (författare)
  • Utmaningar och möjligheter med levande väggar i ett svenskt klimat
  • 2014
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • The interest in alternative green solutions in cities is increasing in Sweden due to increased urban densification. As cities become dense it is usually at the expense of green areas. Creating green infrastructure on buildings, for example with help from different types of green walls, is a way to solve this problem. Many benefits of green walls are highlighted by its proponents, including a positive impact on the environment and health. The newest addition among green walls is so called living walls where the root system grows on substrate in modules or other system placed on the facade. These differ from the more traditional green facades with plants that are planted in the soil and then grow vertically up the facade. It is only in recent years that living walls have been built in outdoor public places in Sweden and a lot of knowledge and experience are still missing concerning the process and organization to plan, build and maintain living walls in Sweden. This study presents the experiences of challenges and opportunities connected to the planning, implementation and maintenance of living walls in a Swedish climate. Interviews with stakeholders involved in five existing Swedish living wall projects have been included in the study together with a literature review. The result of the study indicates a number of challenges and opportunities in connection to living walls in a Swedish climate based on six general areas - technology, plants, organizational and regulatory framework, knowledge and experience, finance, and operation and maintenance. Among other things, a lack of knowledge and experience of living walls is identified, both among the public and potential new customers as well as in the industry, which impedes with the development of living walls in Sweden. More good examples and increased dissemination of the knowledge and experience from existing living wall projects is requested. Meanwhile, it is already possible to see a positive trend with an increasing number living walls in Sweden where the knowledge and experience is increasing with each new project. This study also shows the importance of good cooperation and communication between the stakeholders involved, where especially the organization that is responsible for maintenance plays a very important role for the survival of a living wall. Experiences show that close cooperation, at an early stage of planning, between those who put up the wall and those who will later be responsible for maintenance gives a better end result, while the non-existent collaboration is regarded as a considerable obstacle for the later maintenance. More challenges include the management of advanced irrigation systems, plant survival during the winter and a high investment cost. This report is only available in Swedish.
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30.
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31.
  • Anter, Karin Fridell, et al. (författare)
  • SYN-TES INTERDISCIPLINARY RESEARCH ON COLOUR AND LIGHT
  • 2012
  • Ingår i: Proceedings for Interim Meeting of the International Colour Association (AIC); AIC 2012 “In Color We Live: Color and Environment”, 22 – 25 September 2012, Taipei, Taiwan. - : The International Colour Association. ; , s. 80-83, s. 80-83
  • Konferensbidrag (refereegranskat)abstract
    • Colour and light have largely been considered as belonging to two different fields of knowledge, having disparate theoretical, terminological and methodological traditions. This creates a ground for misunderstandings and obstructs a fruitful interdisciplinary and interprofessional collaboration. A survey over international research literature from 2006 -2011 shows that there has been only little research on the spatial interaction between colour and light, but that the interest for this area has recently increased. The interdisciplinary Nordic research project SYN-TES: Human colour and light synthesis. Towards a coherent field of knowledge was carried out during 2010-11. Colour and light experts from Nordic universities and companies investigated different aspects of the spatial interaction between colour and light and its importance for human beings. This paper deals with the general learnings from the process. Specific results are presented in other papers at this conference.
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32.
  • Bailey Jönsson, Johanna, et al. (författare)
  • Emulsion Condensation Polymerization in Dispersed Aqueous Media. Interfacial Reactions and Nanoparticle Formation
  • 2013
  • Ingår i: Macromolecules. - : American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 46:22, s. 9104-9113
  • Tidskriftsartikel (refereegranskat)abstract
    • The polycondensation of polyesters from C-12 monomers at 95 degrees C in aqueous o/w emulsions, stabilized by acidic surfactants, has been studied in detail with a range of methods during the course of the reaction, resulting in a better understanding of the underlying reaction mechanisms. Comparisons of different surfactants, and effects of added NaCl, demonstrate that the reaction site is located at the interface between the hydrophobic core of the emulsion droplets and the surrounding water and that the reaction rate is dependent on the local concentration of oxonium ions at the reaction site. The equilibrium conversion achieved at long reaction times is, however, independent of the choice of surfactant or addition of salt, and the state of thermodynamic equilibrium is discussed thoroughly. Interestingly, a fraction of numerous "nanoparticles" (droplets in the size range <= 100 nm) have been found to develop in addition to the original fraction of droplets in the 10 mu m size range. It is suggested that these nanoparticles are formed when monomers dissolved in the aqueous phase undergo an acid-catalyzed reaction to generate water-insoluble oligomers. Once the nanoparticles are formed, the reactions in them proceed with a reaction mechanism similar to emulsion polymerization.
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33.
  • Bakoyan, Zaki, et al. (författare)
  • Childhood atopic disorders in relation to placental changes-A systematic review and meta-analysis
  • 2024
  • Ingår i: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - : Munksgaard Forlag. - 0905-6157 .- 1399-3038. ; 35:5, s. 1-17
  • Forskningsöversikt (refereegranskat)abstract
    • Fetal programming may arise from prenatal exposure and increase the risk of diseases later in life, potentially mediated by the placenta. The objective of this systematic review was to summarize and critically evaluate publications describing associations between human placental changes and risk of atopic disorders during childhood. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. The inclusion criteria were original research articles or case reports written in English describing a human placental change in relation to disease occurring in offspring during childhood. The MEDLINE and EMBASE databases were searched for eligible studies. Risk of bias (RoB) was assessed using the ROBINS-I tool. The results were pooled both in a narrative way and by a meta-analysis. Nineteen studies were included (n = 12,997 participants). All studies had an overall serious RoB, and publication bias could not be completely ruled out. However, five studies showed that histological chorioamnionitis in preterm-born children was associated with asthma-related problems (pooled odds ratio = 3.25 (95% confidence interval = 2.22-4.75)). In term-born children, a large placenta (≥750 g) increased the risk of being prescribed anti-asthma medications during the first year of life. Placental histone acetylation, DNA methylation, and gene expression differences were found to be associated with different atopic disorders in term-born children. There is some evidence supporting the idea that the placenta can mediate an increased risk of atopic disorders in children. However, further studies are needed to validate the findings, properly control for confounders, and examine potential mechanisms.
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34.
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35.
  • Beiron, Johanna, 1992, et al. (författare)
  • The role of BECCS in providing negative emissions in Sweden under competing interests for forest-based biomass
  • 2022
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Negative emissions are needed to meet climate mitigation targets and can be achieved through the capture and storage of biogenic CO2 emissions (BECCS). Sweden holds a large potential for BECCS from the industry and heat and power sectors. This work provides a first assessment of how the conditions for BECCS in Sweden are impacted by competition for forest-based biomass from other sectors, in this work represented by production of transportation fuels. An optimization model is applied to study how demand levels for negative emissions and biofuels, and availability of forestry resources, influence the optimal system design considering the electricity, district heating and biomass sectors. BECCS and direct air capture technologies are available for investments in the model. The results show that biomass availability and biofuel demand have a large impact on the choice of negative emission technology, where high competition for biomass favours DACCS rather than BECCS. The available biomass is prioritized for use in fuel production and sets the upper limit for BECCS. In this work, CHP plants are more competitive for BECCS implementation than pulp mills, due to the energy penalty for CHP plants having a smaller impact on the overall energy system performance. The findings indicate that in addition to considering techno-economic assessments of individual technologies, it is important to take into account the system context in which they operate.
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36.
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37.
  • Bergman, Karin, et al. (författare)
  • Invasive pneumococcal disease in persons with predisposing factors is dominated by non-vaccine serotypes in Southwest Sweden
  • 2021
  • Ingår i: Bmc Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe pneumococcal conjugate vaccine PCV7 was introduced in Southwest Sweden in the child vaccination program in 2009, followed by PCV13 in 2010 and PCV10 in 2015. In this retrospective cohort study we assessed the pneumococcal serotype distribution in relation to predisposing factors, clinical manifestations and outcome during seven years after PCV introduction.MethodsClinical data from 1278 patients with 1304 episodes of invasive pneumococcal disease (IPD) between January 2009 and December 2015 in Region Vastra Gotaland, Sweden, were retrospectively collected from medical records. Pneumococcal isolates were serotyped by gel diffusion and/or Quellung reactions performed at the Public Health Agency in Sweden. Associations between serotypes and clinical characteristics were statistically evaluated by use of Fisher's exact test, Mann-Whitney U test and Logistic regression analysis, whereas IPD episodes caused by serotypes over time were analyzed by Mantel-Haenszel chi-square test.ResultsWith the exception of serotype 3, the prevalence of PCV13 serotypes decreased during the study period, from 76% (n=157) of all IPD episodes in 2009 to 25% (n=42) in 2015 (p<0.001) while non-PCV13 serotypes increased, mainly among patients 65years and in patients with predisposing factors, including cardiovascular disease, pulmonary disease and malignancy (p<0.001 for all). Patients with predisposing factors, including those with malignancy, immune deficiency or renal disease, were more likely to have IPD caused by a serotype not included in PCV13 rather than a vaccine-included serotype. Serotype 3 was associated with intensive care unit admissions while serotype 1 and 7F caused IPD among healthier and younger patients. PCV13 serotypes were associated with invasive pneumonia, and non-PCV13 serotypes were associated with bacteremia with unknown focus and with manifestations other than pneumonia or meningitis.ConclusionsNon-PCV13 serotypes caused the majority of IPD cases in Southwest Sweden, especially in patients 65years and in patients with predisposing factors. Serotype 3, included in PCV13, was prevalent and often caused severe disease.
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38.
  • Bergstedt, Johan, et al. (författare)
  • Förändringar i Eklandskapet 1927 till 2013: i den första riksskogstaxeringens fotspår
  • 2017
  • Ingår i: Svensk Botanisk Tidskrift. - 0039-646X. ; 111:6, s. 331-343
  • Tidskriftsartikel (refereegranskat)abstract
    • Transects covering 90 km inan area south of Linköping in the province of Östergötland, SE Sweden, were relocated and reinventoried in 2013 using the same methodology as in the first national forest inventory of 1927. Data for land-use, forest type and species-specific tree sizes were obtained and compared with values from 1927. The results show that arable fields and pastures have decreased, while forests and areas covered by roads etc. have increased considerably. Picea abies has increased more than Pinus sylvestris. The reasons for the changes are discussed.
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39.
  • Bianchi, Matteo, et al. (författare)
  • Contribution of rare genetic variation to disease susceptibility in a large Scandinavian myositis cohort
  • 2022
  • Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 74:2, s. 342-352
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of complex autoimmune conditions characterized by inflammation in skeletal muscle and extramuscular compartments, and interferon (IFN) system activation. We undertook this study to examine the contribution of genetic variation to disease susceptibility and to identify novel avenues for research in IIMs.Methods Targeted DNA sequencing was used to mine coding and potentially regulatory single nucleotide variants from ~1,900 immune-related genes in a Scandinavian case–control cohort of 454 IIM patients and 1,024 healthy controls. Gene-based aggregate testing, together with rare variant– and gene-level enrichment analyses, was implemented to explore genotype–phenotype relations.Results Gene-based aggregate tests of all variants, including rare variants, identified IFI35 as a potential genetic risk locus for IIMs, suggesting a genetic signature of type I IFN pathway activation. Functional annotation of the IFI35 locus highlighted a regulatory network linked to the skeletal muscle–specific gene PTGES3L, as a potential candidate for IIM pathogenesis. Aggregate genetic associations with AGER and PSMB8 in the major histocompatibility complex locus were detected in the antisynthetase syndrome subgroup, which also showed a less marked genetic signature of the type I IFN pathway. Enrichment analyses indicated a burden of synonymous and noncoding rare variants in IIM patients, suggesting increased disease predisposition associated with these classes of rare variants.Conclusion Our study suggests the contribution of rare genetic variation to disease susceptibility in IIM and specific patient subgroups, and pinpoints genetic associations consistent with previous findings by gene expression profiling. These features highlight genetic profiles that are potentially relevant to disease pathogenesis.
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40.
  • Bingerud, Mattias, 1986, et al. (författare)
  • Tracks: Impactful Reform for Flexible Adaptable Education
  • 2023
  • Ingår i: Transforming Engineering Education 2023. - 2446-3833. - 9788775730230 ; , s. 23-27
  • Konferensbidrag (refereegranskat)abstract
    • In this contribution we discuss the progress and achievements of the first three and half years of the Tracks initiative for reformed education at Chalmers University of Technology. In Tracks, the education is designed to give students opportunities to develop inter-disciplinary competencies and to follow individualized study tracks. The purpose of Tracks is also that Chalmers, in collaboration with strategic external partners, shorten the lead times for changing the education to embrace new technologies, emerging materials and concepts and to offer a meeting place for education, research, industry, and society. Three and a half years into the initiative, we conclude that the initial intentions have been achieved. In addition, the project brought unexpected positive effects in, e.g., terms of opportunities for newly recruited faculty and collaboration with sports associations and athletes.
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41.
  • Björklund, Johanna, et al. (författare)
  • An evaluation of structured language modeling for automatic speech recognition
  • 2017
  • Ingår i: Journal of universal computer science (Online). - Graz : Graz university of technology, Institute for information systems computer media IICM. - 0948-695X .- 0948-6968. ; 23:11, s. 1019-1034
  • Tidskriftsartikel (refereegranskat)abstract
    • We evaluated probabilistic lexicalized tree-insertion grammars (PLTIGs) on a classification task relevant for automatic speech recognition. The baseline is a family of n-gram models tuned with Witten-Bell smoothing. The language models are trained on unannotated corpora, consisting of 10,000 to 50,000 sentences collected from the English section of Wikipedia. For the evaluation, an additional 150 random sentences were selected from the same source, and for each of these, approximately 3,200 variations were generated. Each variant sentence was obtained by replacing an arbitrary word by a similar word, chosen to be at most 2 character edits from the original. The evaluation task consisted of identifying the original sentence among the automatically constructed (and typically inferior) alternatives. In the experiments, the n-gram models outperformed the PLTIG model on the smaller data set, but as the size of data grew, the PLTIG model gave comparable results. While PLTIGs are more demanding to train, they have the advantage that they assign a parse structure to their input sentences. This is valuable for continued algorithmic processing, for example, for summarization or sentiment analysis.
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42.
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43.
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44.
  • Blomberg, Oscar, et al. (författare)
  • Adaptation of a guided low-intensity behavioral activation intervention for people with dementia in Sweden : a qualitative study exploring the needs and preferences of key stakeholders
  • 2024
  • Ingår i: BMC Geriatrics. - : Springer. - 1471-2318. ; 24:113
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundDespite depression being prevalent in people with dementia, contributing to negative health outcomes and placing increased burden on individuals and family members, access to psychological interventions is limited. A potential solution is guided low-intensity behavioral activation, supported by informal caregivers and guided by healthcare professionals. However, it is necessary to adapt interventions to meet the needs and preferences of key stakeholders to enhance acceptability and relevance. Study objectives were to: (1) explore needs and preferences concerning the content and delivery model of the guided low-intensity behavioral activation intervention; and (2) adapt the intervention to ensure cultural appropriateness, relevancy, and acceptability to people with dementia and their caregivers in Sweden.MethodsSemi-structured interviews and focus group discussions were conducted with key stakeholders, including healthcare professionals (n = 18), community stakeholders (n = 7), people with dementia (n = 8), and informal caregivers (n = 19). A draft of the written low-intensity behavioral activation intervention and a description of the proposed intervention delivery model were provided to participants. Open-ended questions explored the perceived relevance of the intervention, alongside needs and preferences concerning content and delivery. A manifest content analysis approach was adopted.ResultsContent analysis resulted in three categories: Content, Delivery procedures, and Illness trajectory. Results highlighted a need to consider the intervention Content via increased cultural adaptation to the Swedish context, and increasing the inclusiveness of intervention content. Delivery procedures were identified as needing to be flexible given the unpredictable nature of caring for people with dementia, with the provision of additional guidance to informal caregivers supporting the intervention. Illness trajectory was viewed as essential to consider, with the intervention regarded as suitable for those early in the dementia trajectory, alongside a need to reduce workbook text to minimize burden given dementia symptomology.ConclusionsThe intervention and proposed delivery model were generally well received by all stakeholders. We were able to identify key adaptations to enhance cultural appropriateness, relevancy, and acceptability for a currently neglected population. Results will inform a feasibility study to explore the feasibility and acceptability of the intervention and study procedures to inform the design of a future superiority randomized controlled trial.
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45.
  • Blomstrand, Johanna, et al. (författare)
  • The Michigan Hand Outcomes Questionnaire (MHQ-Swe) in patients with distal radius fractures-cross-cultural adaptation to Swedish, validation and reliability
  • 2021
  • Ingår i: Journal of Orthopaedic Surgery and Research. - : Springer Science and Business Media LLC. - 1749-799X. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The Michigan Hand Outcomes Questionnaire-MHQ-is a well-known self-assessment questionnaire, where patients' own perception in terms of recovery, pain and the ability to return to activities of daily living is assessed. The purpose of the study was to translate and culturally adapt the Michigan Hand Outcomes Questionnaire to Swedish and to test the validity and reliability in patients with surgically treated distal radius fractures. Methods: The cross-cultural adaptation and the translation process were conducted according to predefined guidelines. Seventy-eight patients with surgically treated distal radius fractures completed the translated version of the questionnaire on their six-week follow-up visit. Results: The translation and cross-cultural adaptation process revealed no major linguistic or cultural issues. The internal consistency of the MHQ-Swe ranged from 0.77 to 0.94 at test 1 and from 0.81 to 0.96 at test 2 for all subscales, which indicates good internal consistency in the subscales. The hand function subscale revealed the lowest results and work performance the highest. The ICCs showed excellent test-retest reliability, ranging from 0.77 to 0.90 on all MHQ subscales and 0.92 on total score. The highest results for the ICC were seen in the satisfaction subscale (ICC = 0.90), while the lowest were seen in the aesthetic subscale (ICC = 0.77). The correlation analysis between the MHQ-Swe, PRWE and VAS showed a generally moderate to high correlation for all the subscales. Conclusions: The Swedish version of the MHQ, the MHQ-Swe, showed good validity and reliability and it is therefore an appropriate and relevant questionnaire for use in patients with surgically treated distal radius fractures. Trial registration: FoU i VGR, Projectnumber: 208491, registered December 9, 2015.
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46.
  • Borggren, Marie, et al. (författare)
  • Evolution of DC-SIGN use revealed by fitness studies of R5 HIV-I variants emerging during AIDS progression
  • 2008
  • Ingår i: Retrovirology. - : Springer Science and Business Media LLC. - 1742-4690. ; 5:28
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: At early stages of infection CCR5 is the predominant HIV-1 coreceptor, but in approximately 50% of those infected CXCR4-using viruses emerge with disease progression. This coreceptor switch is correlated with an accelerated progression. However, those that maintain virus exclusively restricted to CCR5 (R5) also develop AIDS. We have previously reported that R5 variants in these "non-switch virus" patients evolve during disease progression towards a more replicative phenotype exhibiting altered CCR5 coreceptor interactions. DC-SIGN is a C-type lectin expressed by dendritic cells that HIV-1 may bind and utilize for enhanced infection of T cells in trans. To further explore the evolution of the R5 phenotype we analyzed sequential R5 isolates obtained before and after AIDS onset, i.e. at the chronic stage and during end-stage disease, with regard to efficiency of DC-SIGN use in trans-infections. Results: Results from binding and trans-infection assays showed that R5 viruses emerging during end-stage AIDS disease displayed reduced ability to use DC-SIGN. To better understand viral determinants underlying altered DC-SIGN usage by R5 viruses, we cloned and sequenced the HIV-1 env gene. We found that end-stage R5 viruses lacked potential N-linked glycosylation sites (PNGS) in the gp120 V2 and V4 regions, which were present in the majority of the chronic stage R5 variants. One of these sites, amino acid position 160 (aa160) in the V2 region, also correlated with efficient use of DC-SIGN for binding and trans-infections. In fitness assays, where head-to-head competitions between chronic stage and AIDS R5 viruses were setup in parallel direct and DCSIGN-mediated infections, results were further supported. Competitions revealed that R5 viruses obtained before AIDS onset, containing the V2 PNGS at aa160, were selected for in the transinfection. Whereas, in agreement with our previous studies, the opposite was seen in direct target cell infections where end-stage viruses out-competed the chronic stage viruses. Conclusion: Results of our study suggest R5 virus variants with diverse fitness for direct and DCSIGN-mediated trans-infections evolve within infected individuals at end-stage disease. In addition, our results point to the importance of a glycosylation site within the gp120 V2 region for efficient DC-SIGN use of HIV-1 R5 viruses.
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47.
  • Borggren, Marie, et al. (författare)
  • Increased Sensitivity to Broadly Neutralizing Antibodies of End-Stage Disease R5 HIV-1 Correlates with Evolution in Env Glycosylation and Charge.
  • 2011
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Induction of broadly neutralizing antibodies, such as the monoclonal antibodies IgGb12, 2F5 and 2G12, is the objective of most antibody-based HIV-1 vaccine undertakings. However, despite the relative conserved nature of epitopes targeted by these antibodies, mechanisms underlying the sensitivity of circulating HIV-1 variants to broadly neutralizing antibodies are not fully understood. Here we have studied sensitivity to broadly neutralizing antibodies of HIV-1 variants that emerge during disease progression in relation to molecular alterations in the viral envelope glycoproteins (Env), using a panel of primary R5 HIV-1 isolates sequentially obtained before and after AIDS onset.
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48.
  • Bremin, Sofia, et al. (författare)
  • Methods for human evaluation of machine translation
  • 2010
  • Ingår i: Proceedings of the Swedish Language Technology Conference (SLTC2010). ; , s. 47-48
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Evaluation of machine translation (MT) is a difficult task, both for humans, and using automatic metrics. The main difficulty lies in the fact that there is not one single correct translation, but many alternative good translation options.MT systems are often evaluated using automatic metrics, which commonly rely on comparing a translation to only a single human reference translation. An alternative is different types of human evaluations, commonly ranking be-tween systems or estimations of adequacy and fluency on some scale, or error analyses.We have explored four different evaluation methods on output from three different statistical MT systems. The main focus is on different types of human evaluation. We compare two conventional evaluation methods, human error analysis and automatic metrics, to two lesser used evaluation methods based on reading comprehension and eye-tracking. These two methods of evaluations are performed without the subjects seeing the source sentence. There have been few previous attempts of using reading comprehension and eye-tracking for MT evaluation.One example of a reading comprehension study is Fuji (1999) who conducted an experiment to compare English-to-Japanese MT to several versions of manual corrections of the system output. He found significant differences be-tween texts with large differences on reading comprehension questions. Doherty and O’Brien (2009) is the only study we are aware of using eye-tracking for MT evaluation. They found that the average gaze time and fixation counts were significantly lower for sentences judged as excellent in an earlier evaluation, than for bad sentences.Like previous research we find that both reading comprehension and eye-tracking can be useful for MT evaluation.The results of these methods are consistent with the other methods for comparison between systems with a big quality difference. For systems with similar quality, however, the different evaluation methods often does not show any significant differences.
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49.
  • Brinne Roos, Johanna, 1976- (författare)
  • Electron Recombination with Small Molecular Ions
  • 2007
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In this thesis I have theoretically studied electron recombination processes with small molecular ions. In these kind of processes resonant states are involved. To calculate the potential energy for these states as a function of internuclear distance, structure calculations and scattering calculations have to be performed. So far I have been studying the ion-pair formation with in electron recombination with H3+. The cross section for this process has been calculated using different kind of models, both a time dependent quantum mechanical and a semiclassical. I have also studied the direct process of dissociative recombination of HF+. To calculate the total cross section for this process, we have performed wave packet propagation on thirty resonant states and summed up the individual cross sections for these states. The cross sections for both these processes have a similar appearance to those measured experimentally in the ion storage ring CRYRING in Stockholm.
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50.
  • Brogren, Helén, 1977, et al. (författare)
  • Heterogeneous glycosylation patterns of human PAI-1 may reveal its cellular origin.
  • 2008
  • Ingår i: Thrombosis research. - : Elsevier BV. - 0049-3848. ; 122:2, s. 271-81
  • Tidskriftsartikel (refereegranskat)abstract
    • The main inhibitor of intravascular fibrinolysis is plasminogen activator inhibitor 1 (PAI-1) which binds to and irreversibly inhibits tissue plasminogen activator (tPA). PAI-1 is present in blood, both in platelets and in plasma, and PAI-1 levels are associated with risk of atherothrombosis. Several tissues express PAI-1 but the source of plasma PAI-1 is not known. We recently found that platelets can de novo synthesize PAI-1 and the amount synthesized in vitro in 24 hours is 35-fold higher than required to maintain normal plasma levels. Recombinant human PAI-1 expressed in different cell types or secreted naturally by human cell lines, exhibit heterogeneous glycosylation patterns. The aim of this study was to investigate the hypothesis that platelets might be the source of plasma PAI-1 and that the cellular source of PAI-1 can be determined by its tissue-specific glycosylation pattern. PAI-1 was isolated from platelets, macrophages, endothelial cells, adipose tissue, as well as plasma from lean and obese subjects. The glycosylation was analyzed by nanoLC-MS/MS. PAI-1 isolated from cell lysates and conditioned media from macrophages, endothelial cells, and adipose tissue expressed heterogeneous glycosylation patterns. By contrast, no glycans were detected on PAI-1 isolated from plasma or platelets from healthy lean individuals. Hence, our data suggest that platelets may be the main source of plasma PAI-1 in lean individuals. Interestingly, plasma PAI-1 from obese subjects had a glycan composition similar to that of adipose tissue suggesting that obese subjects with elevated PAI-1 levels may have a major contribution from other tissues.
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