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1.
  • Johansson, Adam Johannes, et al. (författare)
  • Insights from post-test examination of three packages from the MiniCan test series of copper-cast iron canisters for geological disposal of spent nuclear fuel : impact of the presence and density of bentonite clay
  • 2017
  • Ingår i: Corrosion Engineering, Science and Technology. - 1478-422X .- 1743-2782. ; 52, s. 54-60
  • Tidskriftsartikel (refereegranskat)abstract
    • MiniCan is a field test designed to highlight certain aspects of corrosion in a KBS-3 type repository for spent nuclear fuel. Five experimental packages containing miniature copper-cast iron canisters were installed in the Äspö Hard Rock Laboratory in 2006. Three packages have been retrieved, MiniCan 3 in 2011 and MiniCan 4 and 5 in 2015. The packages were examined regarding surface chemistry, microbiology and corrosion of copper and iron. The main difference in design between the retrieved packages was the presence and density of bentonite clay. Black deposits of sulphides were visually noted during dismantling of both MiniCan 3 (low density clay) and MiniCan 5 (no clay), but not in MiniCan 4 (high density clay). Extensive corrosion of cast iron specimens was observed in all three packages, with local attacks corresponding to the loss of hundreds of µm/y. Sulphate reducing bacteria (SRB) were found to be present in ground water, in bentonite clay and on surfaces of various specimens of iron and copper, and it is suggested that the SRB activity had a pronounced influence on the corrosion observed. Copper surfaces display a roughness at the µm level and the integrated corrosion rate of copper mass-loss specimens was generally low. This paper is part of a supplement on the 6th International Workshop on Long-Term Prediction of Corrosion Damage in Nuclear Waste Systems. © 2017 The Author(s).
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2.
  • Nilsson, Kerstin, et al. (författare)
  • 54 forskare: Inte alla klarar höjd pensions-ålder
  • 2017
  • Ingår i: Svenska Dagbladet, Stockholm. - 1101-2412.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Ett hållbart och acceptabelt pensionssystem måste utformas utifrån personliga förutsättningar och förhållanden i arbetslivet, så att fler klarar att arbeta i högre ålder. Att enbart genom ekonomiska åtgärder höja pensionsåldern är inte långsiktigt hållbart, skriver 54 forskare.DEBATT | PENSIONForskning visar att cirka var fjärde har en diagnos eller skada orsakad av sitt arbete. Detta gör arbetsorsakad sjukdom och skada till ett betydelsefullt folkhälsoproblem. Att då enbart genom ekonomiska åtgärder höja pensionsåldern för samtliga (yrkes)grupper utifrån deras kronologiska ålder är inte långsiktigt hållbart när individers biologiska ålder är så olika bland annat till följd av arbetslivet. Detta är en demokratifråga. Forskning om äldre i arbetslivet och hållbart arbete visar att man då främst flyttar individer från pensionssystemet till sjukförsäkringssystemet och ökar klyftorna i samhället.Debatt Det här är en argumenterande text med syfte att påverka. Åsikterna som uttrycks är skribentens egna.Vi är 54 forskare som nu gemensamt har skrivit denna debattartikel. Anledningen är att vi är oroade över att cirka var fjärde blir sjuk av sitt arbete samtidigt som man i det förslag som ligger om att senarelägga ålderspensionen i princip utgår ifrån att arbetskraftsdeltagande enbart styrs av ekonomin. Vi vill trycka på betydelsen av åtgärder i arbetslivet för att komma tillrätta med ohälsan, det vill säga inte enbart ekonomiska restriktioner som tvingar folk som inte kan, vill och orkar att stanna kvar i arbetslivet till en högre kronologisk ålder.Pensionssystemet bygger på att vi ska arbeta en viss del av våra liv för att förtjäna möjligheter till pension. Vi bör dock inte enbart utgå ifrån antalet år sedan en person föddes, då korttidsutbildade generellt träder in på arbetsmarknaden tidigare än långtidsutbildade. De har alltså varit en del av arbetskraften från en yngre ålder. Människor med kortare utbildning har oftare ett arbete som innebär påfrestningar som kan inverka negativt på hälsotillståndet och som till och med kan påskynda det biologiska åldrandet. Dessutom lever korttidsutbildade generellt sett inte lika länge som långtidsutbildade, vilket delvis även avspeglar skilda livs- och arbetsvillkor.Den svenska sjukförsäkringsreformen 2008 avsåg att få tillbaka människor i arbete. Men studien fann att den faktiskt bidrog till att fler gick i tidig ålderspension av dem som var i åldern 55–64 år. Ökningen var störst bland korttidsutbildade. Mer än 5 procent fler gick i tidig ålderspension då det blev svårare att få sjukpenning och sjukersättning. Vi kan notera att det är vanligare att manliga chefer tar ut tidig ålderspension, jämfört med kvinnliga maskinskötare inom tillverkningsindustrin. I vissa yrken är det dessutom vanligare att människor, trots pension, både orkar och faktiskt ges möjlighet att arbeta vidare om de har en specialkompetens som efterfrågas. Om vi endast kombinerar ekonomiska morötter med piskor finns en stor risk att vi ökar klyftan mellan grupper som både kan och vill fortsätta att yrkesarbeta och personer som av olika skäl inte längre kan eller orkar.Ta nytta av den forskning som vi har tagit fram. Ett hållbart och acceptabelt pensionssystem måste utformas utifrån personliga förutsättningar och förhållanden i arbetslivet. Ett hållbart arbetsliv för allt fler i vår åldrande befolkning fordrar att vi samtidigt beaktar faktorer som relaterar till biologisk/kroppslig ålder, mental/kognitiv ålder samt social ålder/livsloppsfas och våra attityder som är kopplade till ålder. Vi måste ta större hänsyn till olika förutsättningar och varierande funktionsförmåga och utifrån detta anpassa de åtgärder som gör att arbetslivet blir möjligt och hållbart för allt fler även i högre ålder.”Morötter” är viktigare för en god arbetshälsa och hög produktivitet än en piska i form av oron för en dålig ekonomi.Forskning visar att pedagogik som bygger på ”morötter” oftast är betydligt bättre än ”piskor” för att nå framgångsrika och långsiktiga mål. ”Morötter” i samhället, för organisationer, företag och individer är därför viktiga för god arbetshälsa och fortsatt produktivitet och kan bidra till ett längre arbetsliv även för grupper som tidigare inte ens klarat av att arbeta fram till pensionsåldern. Genom forskning inom området har bland annat swage-modellen utarbetats. Detta är ett verktyg som visar på komplexiteten i ett hållbart arbetsliv och tillsammans med systematiskt arbetsmiljöarbete, handlingsplaner och åtgärder syftar till ett mer hållbart arbetsliv. Morötter är enligt forskningen i detta sammanhang åtgärder för en god fysisk och mental arbetsmiljö, avpassad arbetsbelastning, stödjande teknik, att man kan anpassa arbetstakten, alternativa arbetstidsmodeller vid behov. Det är viktigt att man känner sig trygg och förväntas och tillåts vara delaktig, att man blir sedd av chefen och arbetskamraterna. Att de egna arbetsuppgifterna upplevs som meningsfulla och behövda av andra skapar självförverkligande och tillfredsställelse i arbetet. Att man känner att ens arbetsuppgifter och man själv är viktig för organisationen och företaget. Att man trots högre ålder inkluderas i olika nysatsningar och får tillgång till kompetensutveckling och inte blir åsidosatt eller åldersdiskriminerad. Utvärderingar visar att de äldre medarbetarna som fick några av dessa anpassningar och möjligheter var mer effektiva, utvilade, stimulerade när de var på arbetet samtidigt som sjukfrånvaron minskade. Vilket i sin tur bidrar till ett längre arbetsliv för grupper som tidigare inte klarat av att arbeta fram till pensionsåldern. I organisationer som bygger på en deltagar- och lärandekultur rustas de anställda för att klara omställningar, nya arbetsuppgifter och vid behov även yrkesbyten.Med en åldrande befolkning där allt fler lever allt längre behöver vi arbeta till en högre ålder i framtiden för att pensionssystemet ska hålla. Men ”morötter” är viktigare för en god arbetshälsa och hög produktivitet än en piska i form av oron för en dålig ekonomi. Det kräver också att vi ändrar våra attityder och förhållningssätt till äldre på arbetsmarknaden, vilket vi bäst gör genom att organisationer och företag får incitament till och erbjuder mer individanpassade arbetsvillkor, särskilt för personer i högre ålder. Låt oss därför använda den framtagna kunskapen i praktiken för att göra arbetslivet friskt och hållbart för alla åldrar.
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  • Nilsson, Kerstin, et al. (författare)
  • Vi är oroade över senare ålderspension
  • 2017
  • Ingår i: Dagens Samhälle. - 1652-6511.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Var fjärde person blir i dag sjuk till följd av sitt arbete. Att höja pensionsåldern för alla yrkesgrupper, utan konkreta åtgärder för att minska ohälsan, är därför problematiskt och mycket oroande. Det är, enligt forskarna, inte långsiktigt samhällsekonomiskt lönsamt att utan andra åtgärder höja pensionsåldern för alla. Vi – 54 forskare – är mycket oroade över konsekvenserna av att, som föreslagits, senarelägga ålderspensionen.Förslaget utgår i princip från arbetskraftsdeltagande i princip enbart styrs av ekonomin, medan forskningen visar att det bara är en av flera faktorer som styr hur länge och hur mycket människor väljer att arbeta.Det här sättet att lösa problemet med en åldrande befolkning och ett sviktande pensionssystem är inte samhällsekonomiskt lönsamt på lång sikt, utan riskerar bara att flytta runt folk mellan olika ersättningssystem. Pensionssystemet bygger på att vi ska arbeta en viss del av våra liv för att tjäna in vår pension. Vi bör dock inte enbart utgå ifrån ålder eller antalet år sedan en person föddes då korttidsutbildade generellt träder in på arbetsmarknaden tidigare än långtidsutbildade. De med kortare utbildningstid har alltså varit en del av arbetskraften från en yngre ålder. Människor med kortare utbildning har också oftare ett arbete som innebär påfrestningar som kan inverka negativt på hälsotillståndet och som till och med kan påskynda det biologiska åldrandet. Dessutom lever korttidsutbildade generellt sett inte lika länge som långtidsutbildade, vilket delvis även avspeglar skilda livs- och arbetsvillkor.Ta nytta av den forskning som vi har tagit fram. Ekonomin är självklart viktigt för att vi ska vilja arbeta, men den är som sagt enbart en av flera faktorer med betydelse vårt arbetsliv.Hälsotillståndet, både det fysiska och det mentala, har en avgörande betydelse för hur länge och hur mycket vi orkar arbeta. Ett fysiskt och mentalt belastande arbete är en stark riskfaktor för en nedsatt hälsa i slutet av arbetslivet. Arbetstid, arbetstakt och möjlighet till återhämtning spelar en allt större roll ju äldre vi blir. Andra aspekter är arbetsinnehåll, hur meningsfulla och stimulerande arbetsuppgifterna är, balansen mellan arbete och familjesituation och fritidsaktiviteter. Organisationskultur, ledarskapet, stöd i arbetet och kompetens har stor betydelse för om vi ska kunna och vilja arbeta till en högre ålder. Vi måste ta större hänsyn till olika förutsättningar och varierande funktionsförmåga och utifrån detta anpassa de åtgärder som gör att arbetslivet blir möjligt och hållbart för allt fler även i högre ålder.Ett hållbart och acceptabelt pensionssystem måste därför utformas utifrån personliga förutsättningar och förhållanden i arbetslivet. Ett hållbart arbetsliv för allt fler i vår åldrande befolkning fordrar att vi samtidigt beaktar faktorer som relaterar till biologisk/kroppslig ålder, mental/kognitiv ålder samt social ålder/livsloppsfas samt de attityder som är kopplade till ålder.
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  • Ahmed Pihlgren, Sara, et al. (författare)
  • Exploring healthcare workers' experiences of a simple intervention to reduce their intrusive memories of psychological trauma: an interpretative phenomenological analysis
  • 2024
  • Ingår i: EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY. - : Taylor & Francis. - 2000-8198 .- 2000-8066. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Many healthcare workers (HCWs) endured psychologically traumatic events at work during the coronavirus disease 2019 (COVID-19) pandemic. For some, these events are re-experienced as unwanted, recurrent, and distressing intrusive memories. Simple psychological support measures are needed to reduce such symptoms of post-traumatic stress in this population. A novel intervention to target intrusive memories, called an imagery-competing task intervention (ICTI), has been developed from the laboratory. The intervention includes a brief memory reminder cue, then a visuospatial task (Tetris (R) gameplay using mental rotation instructions for approximately 20 min) thought to interfere with the traumatic memory image and reduce its intrusiveness. The intervention has been adapted and evaluated in a randomized controlled trial (RCT) with Swedish HCWs (ClinicalTrials.gov identifier: NCT04460014).Objective: We aimed to explore how HCWs who worked during the COVID-19 pandemic experienced the use of a brief intervention to reduce their intrusive memories of work-related trauma.Method: Interpretative phenomenological analysis was used for in-depth understanding of the lived experiences of HCWs who used the intervention. Seven participants from the RCT were interviewed by an independent researcher without prior knowledge of the intervention. Interviews were conducted via telephone and transcribed verbatim.Results: Four general themes were generated: 'Triggers and troublesome images', 'Five Ws regarding support - what, when, why, by/with who, for whom', 'Receiving it, believing it, and doing it' and 'The intervention - a different kind of help'; the last two included two subthemes each. The results reflect participants' similarities and differences in their lived experiences of intrusive memories, support measures, and intervention impressions and effects.Conclusion: HCWs' experiences of the novel ICTI reflect a promising appraisal of the intervention as a potential help measure for reducing intrusive memories after trauma, and gives us a detailed understanding of HCWs' needs, with suggestions for its adaption for future implementation.Trial registration: ClinicalTrials.gov identifier: NCT04460014. Many healthcare workers experience images or 'flashbacks' of traumatic experiences from their work during the COVID-19 pandemic.To ensure that individual needs are met, there is a need to tailor and refine current psychological support measures and their use for healthcare workers.The imagery-competing task intervention was perceived as acceptable, indicating its potential utility as a help measure to reduce intrusive memories after trauma. Antecedentes: Los trabajadores de la salud (HCW, por sus siglas en ingles) sufrieron eventos psicologicamente traumaticos en el trabajo durante la pandemia por COVID-19. Para algunos, estos acontecimientos se vuelven a experimentar como recuerdos intrusivos no deseados, recurrentes y angustiosos. Se necesitan medidas simples de apoyo psicologico para reducir estos sintomas de estres postraumatico en esta poblacion. En el laboratorio se ha desarrollado una nueva intervencion para abordar los recuerdos intrusivos, conocida como Intervencion de Tareas Competitivas de Imagenes (ICTI, por sus siglas en ingles). La intervencion incluye una breve senal de recordatorio de la memoria, luego una tarea visoespacial (juego de Tetris (R) que utiliza instrucciones de rotacion mental durante aproximadamente 20 minutos) que se cree que interfiere con la imagen de la memoria traumatica y reduce su intrusion. La intervencion se ha adaptado y evaluado recientemente en un ECA (ensayo controlado aleatorizado) con trabajadores sanitarios suecos (identificador de ClinicalTrials.gov: NCT04460014). Aqui nuestro objetivo es explorar como los participantes del ECA experimentaron la nueva intervencion.Objetivo: Explorar como los trabajadores sanitarios que trabajaron durante la pandemia por COVID-19 experimentaron el uso de una intervencion breve para reducir sus recuerdos intrusivos del trauma relacionado con el trabajo.Metodo: Se utilizo un analisis fenomenologico interpretativo para comprender en profundidad las experiencias vividas por los trabajadores sanitarios que utilizaron la intervencion. Siete participantes del ECA fueron entrevistados por un investigador independiente sin conocimiento previo de la intervencion. Las entrevistas se realizaron por telefono y se transcribieron palabra por palabra.Resultados: Se generaron cuatro temas generales, 'Desencadenantes e imagenes problematicas', 'Cinco preguntas sobre el apoyo: que, cuando, por que, por/con quien, para quien', 'Recibirlo, creerlo y hacerlo' y 'La intervencion. - una ayuda diferente', los dos ultimos incluian dos subtemas cada uno. Los resultados reflejan similitudes y diferencias de los participantes en sus experiencias vividas de recuerdos intrusivos, medidas de apoyo e impresiones y efectos de la intervencion.Conclusion: Las experiencias de los trabajadores sanitarios con el nuevo ICTI reflejan una evaluacion prometedora de la intervencion como una posible medida de ayuda para reducir los recuerdos intrusivos despues del trauma, y nos brinda una comprension detallada de las necesidades de los trabajadores sanitarios, con sugerencias sobre como adaptarse para una implementacion futura.
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  • Bajinskis, Ainars, et al. (författare)
  • Low-Dose/Dose-Rate gamma Radiation Depresses Neural Differentiation and Alters Protein Expression Profiles in Neuroblastoma SH-SY5Y Cells and C17.2 Neural Stem Cells
  • 2011
  • Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 175:2, s. 185-192
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects of low doses of ionizing radiation on cellular development in the nervous system are presently unclear. The focus of the present study was to examine low-dose gamma-radiation-induced effects on the differentiation of neuronal cells and on the development of neural stem cells to glial cells. Human neuroblastoma SH-SY5Y cells were exposed to (137)Cs gamma rays at different stages of retinoic acid-induced neuronal differentiation, and neurite formation was determined 6 days after exposure. When SH-SY5Y cells were exposed to low-dose-rate gamma rays at the onset of differentiation, the number of neurites formed per cell was significantly less after exposure to either 10, 30 or 100 mGy compared to control cells. Exposure to 10 and 30 mGy attenuated differentiation of immature C17.2 mouse-derived neural stem cells to glial cells, as verified by the diminished expression of glial fibrillary acidic protein. Proteomic analysis of the neuroblastoma cells by 2D-PAGE after 30 mGy irradiation showed that proteins involved in neuronal development were downregulated. Proteins involved in cell cycle and proliferation were altered in both cell lines after exposure to 30 mGy; however, the rate of cell proliferation was not affected in the low-dose range. The radiation-induced attenuation of differentiation and the persistent changes in protein expression is indicative of an epigenetic rather than a cytotoxic mechanism. (C) 2011 by Radiation Research Society
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  • Baldetorp, Bo, et al. (författare)
  • Analysis of protein expression in pure cell nuclei populations isolated from human breast cancer tissue by DNA flow cytometric sorting.
  • 2010
  • Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919. ; 73, s. 1111-1116
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, cell nuclei from aneuploid breast cancer samples were sorted with respect to DNA content into pure diploid and aneuploid fractions using flow cytometry. The nuclear proteins were then separated by one-dimensional gel electrophoresis (1D-PAGE) and differences in protein expression patterns, between diploid and aneuploid nuclei from the same tumours, were compared. Using a combination of peptide finger printing and peptide identification by MALDI-TOF mass spectrometry, we identified proteins and confirmed that the proteins were of nuclear origins. The results in this study add further information to the knowledge about the breast cancer disease complexity and heterogeneity at molecular level. For some of the tumours studied different nuclei protein patterns were obtained, in the diploid respective aneuploid nuclei populations, whilst other tumours did not show these differences.
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  • Berggren, Anna, et al. (författare)
  • Intestinal function, microflora and nutrient intake of children after administration of a fermented oat product containing Lactobacillus plantarum DSM 9843 (299v)
  • 2003
  • Ingår i: Microbial Ecology in Health and Disease. - : Informa UK Limited. - 0891-060X .- 1651-2235. ; 15:4, s. 160-168
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of the study was to evaluate the intestinal tolerance of a newly developed food containing Lactobacillus plantarum 299v, in children. The effects of consumption of the product on the children's nutrient intake were also followed, in a separate study. The tolerance study was parallel, double-blind, and included 69 children between 6 months and 3 years of age, randomized into two groups. One of the groups consumed a fermented oat product (1×109 cfu L. plantarum 299v/g) for 3 weeks, while the other group consumed a placebo product. We analysed the subjects by intention to treat and also carried out an analysis of subjects who had a mean intake of >100 g study product per day. After consumption for 3 weeks, the content of L. plantarum 299v in faeces increased significantly in the test group compared with the placebo group (p<0.001) and mean log10 cfu/g was 8.7 (intention to treat analysis). Also, the total content of lactobacilli increased and was significantly higher compared with the placebo group (p<0.001). The same result was also obtained when the data for the subjects who had a higher consumption of the study products were analysed. There were no differences in reported gastrointestinal function between the groups. The effects of the fermented oat product on the children's nutrient intake were followed in 12 children aged 1-3 years. Inclusion of the fermented oat product that was enriched with iron and ascorbic acid led to a significantly higher intake of several nutrients like energy, carbohydrates (g, E%), dietary fibre, iron and zinc. In conclusion, the children tolerated the fermented oat product well, the faecal microflora was positively altered and the children's nutritional intake was improved. Keywords: children, microflora, Lactobacillus plantarum 299v, probiotic bacteria, intestinal tolerance, nutrient intake.
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  • Bergström, Petra, et al. (författare)
  • Herpes Simplex Virus 1 and 2 Infections during Differentiation of Human Cortical Neurons
  • 2021
  • Ingår i: Viruses-Basel. - : MDPI AG. - 1999-4915. ; 13:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Herpes simplex virus 1 (HSV-1) and 2 (HSV-2) can infect the central nervous system (CNS) with dire consequences; in children and adults, HSV-1 may cause focal encephalitis, while HSV-2 causes meningitis. In neonates, both viruses can cause severe, disseminated CNS infections with high mortality rates. Here, we differentiated human induced pluripotent stem cells (iPSCs) towards cortical neurons for infection with clinical CNS strains of HSV-1 or HSV-2. Progenies from both viruses were produced at equal quantities in iPSCs, neuroprogenitors and cortical neurons. HSV-1 and HSV-2 decreased viability of neuroprogenitors by 36.0% and 57.6% (p < 0.0001), respectively, 48 h post-infection, while cortical neurons were resilient to infection by both viruses. However, in these functional neurons, both HSV-1 and HSV-2 decreased gene expression of two markers of synaptic activity, CAMK2B and ARC, and affected synaptic activity negatively in multielectrode array experiments. However, unaltered secretion levels of the neurodegeneration markers tau and NfL suggested intact axonal integrity. Viral replication of both viruses was found after six days, coinciding with 6-fold and 22-fold increase in gene expression of cellular RNA polymerase II by HSV-1 and HSV-2, respectively. Our results suggest a resilience of human cortical neurons relative to the replication of HSV-1 and HSV-2.
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  • Boerenbeker, P., et al. (författare)
  • Family member's experiences with and evaluation of an ICU Liaison Nurse Service: A qualitative study
  • 2023
  • Ingår i: Nursing in Critical Care. - : Wiley. - 1362-1017 .- 1478-5153. ; 28:6, s. 854-862
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Family members of critically ill patients often experience anxiety when their relatives are transferred from ICU to another level of care. ICU liaison nurse (ICULN) visits have been associated with improved support for patients, their families and nursing staff but has not been extensively studied in the non-English speaking setting. Yet, cross-country variations such as how hospital care is delivered and by who means that innovations such as the ICULN may not be able to be simply transferred to other contexts and may not have similar outcomes. Aim The aim of this study was to investigate family member's experiences with and evaluation of ICULN support service in one Swedish ICU. Study Design A qualitative evaluation study was undertaken, recruiting family members of former ICU patients. Audio-taped in-depth interviews were conducted. Data were analysed by content analysis. Findings Fifteen family members were interviewed. Two categories: Minds the gap between intensive care and the next care level and providing stability in an uncertain situation were identified. The ICULN supported the family members both directly, when the ICULNs listened to their questions and met their needs, and indirectly, when the ICULNs took responsibility for the patients and their physical and psychological conditions and wellbeing. Conclusion Families valued and were satisfied with the ICULN service but also gave suggestions to improve the service in this particular hospital context. Relevance to Clinical Practice The study showed that an ICULN support service met several needs of family members and therefore was a beneficial way to support patients and family members in the transition from the ICU to the ward.
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15.
  • Bäck, Marcus, et al. (författare)
  • Novel potent macrocyclic inhibitors of the hepatitis C virus NS3 protease : use of cyclopentane and cyclopentene P2-motifs
  • 2007
  • Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 15:22, s. 7184-7202
  • Tidskriftsartikel (refereegranskat)abstract
    • Several highly potent novel HCV NS3 protease inhibitors have been developed from two inhibitor series containing either a P2 trisubstituted macrocyclic cyclopentane- or a P2 cyclopentene dicarboxylic acid moiety as surrogates for the widely used N-acyl-(4R)-hydroxyproline in the P2 position. These inhibitors were optimized for anti HCV activities through examination of different ring sizes in the macrocyclic systems and further by exploring the effect of P4 substituent removal on potency. The target molecules were synthesized from readily available starting materials, furnishing the inhibitor compounds in good overall yields. It was found that the 14-membered ring system was the most potent in these two series and that the corresponding 13-, 15-, and 16-membered macrocyclic rings delivered less potent inhibitors. Moreover, the corresponding P1 acylsulfonamides had superior potencies over the corresponding P1 carboxylic acids. It is noteworthy that it has been possible to develop highly potent HCV protease inhibitors that altogether lack the P4 substituent. Thus the most potent inhibitor described in this work, inhibitor 20, displays a Ki value of 0.41 nM and an EC50 value of 9 nM in the subgenomic HCV replicon cell model on genotype 1b. To the best of our knowledge this is the first example described in the literature of a HCV protease inhibitor displaying high potency in the replicon assay and lacking the P4 substituent, a finding which should facilitate the development of orally active small molecule inhibitors against the HCV protease.
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  • Bäckström, Torbjörn, et al. (författare)
  • Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons
  • 2011
  • Ingår i: Neuroscience. - Oxford : Elsevier BV. - 0306-4522 .- 1873-7544. ; 191:Special issue, s. 46-54
  • Forskningsöversikt (refereegranskat)abstract
    • Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%-8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%-8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane C1(-) gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote disinhibition, and hence excitability. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain. (C) 2011 Published by Elsevier Ltd on behalf of IBRO.
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19.
  • Bäckström, Torbjörn, 1948-, et al. (författare)
  • Pathogenesis in menstrual cycle-linked CNS disorders.
  • 2003
  • Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1007, s. 42-53
  • Forskningsöversikt (övrigt vetenskapligt/konstnärligt)
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20.
  • Bäckström, Torbjörn, et al. (författare)
  • The role of hormones and hormonal treatments in premenstrual syndrome
  • 2003
  • Ingår i: CNS Drugs. - 1172-7047 .- 1179-1934. ; 17:5, s. 325-342
  • Tidskriftsartikel (refereegranskat)abstract
    • Premenstrual syndrome (PMS) is a menstrual cycle-linked condition with both mental and physical symptoms. Most women of fertile age experience cyclical changes but consider them normal and not requiring treatment. Up to 30% of women feel a need for treatment. The aetiology is still unclear, but sex steroids produced by the corpus luteum of the ovary are thought to be symptom provoking, as the cyclicity disappears in anovulatory cycles when a corpus luteum is not formed. Progestogens and progesterone together with estrogen are able to induce similar symptoms as seen in PMS. Symptom severity is sensitive to the dosage of estrogen. The response systems within the brain known to be involved in PMS symptoms are the serotonin and GABA systems. Progesterone metabolites, especially allopregnanolone, are neuroactive, acting via the GABA system in the brain. Allopregnanolone has similar effects as benzodiazepines, barbiturates and alcohol; all these substances are known to induce adverse mood effects at low dosages in humans and animals. SSRIs and substances inhibiting ovulation, such as gonadotrophin-releasing hormone (GnRH) agonists, have proven to be effective treatments. To avoid adverse effects when high dosages of GnRH agonists are used, add-back hormone replacement therapy is recommended. Spironolactone also has a beneficial effect, although not as much as SSRIs and GnRH agonists.
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21.
  • Chruzander, Charlotte, et al. (författare)
  • Longitudinal changes in sickness absence and disability pension, and associations between disability pension and disease-specific and contextual factors and functioning, in people with multiple sclerosis.
  • 2016
  • Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 367, s. 319-325
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Even though it is well known that disability due to MS is highly associated with employment status, the long-term longitudinal perspective on sickness absence and disability pension over the MS trajectory is lacking. In addition, further knowledge of risk factors for future disability pension is needed.OBJECTIVES: To explore long-term longitudinal changes in the prevalence of sickness absence and disability pension in people with MS (PwMS), as well as to explore associations between disease-specific factors, contextual factors and functioning, and the outcome of future full-time disability pension.METHODS: A prospective, population-based survival cohort study, with a nine year follow-up, including 114 PwMS was conducted by combining face-to-face collected data and register-based data.RESULTS: The prevalence of full-time disability pension increased from 20% to 50%, however 24% of the PwMS had no disability pension at all at end of follow-up. Sex, age, disease severity and impaired manual dexterity were associated with future full-time disability pension.CONCLUSIONS: The large increase in prevalence of PwMS on full-time disability pension during the MS trajectory, calls for the development and implementation of evidence-based interventions, aiming at keeping PwMS in the work force. Modifiable factors, such as manual dexterity should be targeted in such interventions.
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22.
  • Creelman, Alastair, 1958-, et al. (författare)
  • Open courses as virtual mobility and the role of collaborative literacy in staff development
  • 2016
  • Ingår i: EDEN 2016 Annual Conference. Re-Imagining Learning Scenarios. - Budapest : European Distance and E-Learning Network, 2016. - 9786155511080
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Open Networked Learning (ONL) https://opennetworkedlearning.wordpress.com is an open online course that is offered both as an internal professional development course at the partner universities (Karolinska Institute, Lund University, Linnaeus University, KTH in Sweden and IIE Varsity College in South Africa) as well as being open to learners from all over the world. The course has been derived from an earlier model that has in turn led to several other online courses. The primary target group is university teachers, educational technologists and course designers but it also attracts educators from other educational sectors both public and private. Using an open collaborative learning environment learners investigate aspects of connected, collaborative learning with modules based around topics such as digital literacies, collaborative and flexible learning, teaching in open spaces and course design.
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23.
  • Dessen Jankell, Lotta, 1970- (författare)
  • Förstå verkligheten som system : - att utveckla gymnasieelevers systemgeografiska kunnande genom geografiundervisning
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This doctoral thesis is concerned with how upper secondary students in Sweden develop system geographical knowing through Geography teaching, where complex issues such as climate change are dealt with. In many countries, these issues are particularly relevant for the school subject of Geography since the subject is responsible for issues that involve system changes. These issues involve a complex web of aspects and dimensions so it is challenging for students to develop indepth holistic understandings. Commonly, students are left alone to synthesise the various parts into a whole. Systems thinking is suggested as an approach to dealing with these challenges, but there is little research on what such thinking implies in Geography teaching, or what students need to experience to develop this knowing. This educational design study departs from practice theory to explore and broaden systems thinking in Geography teaching by introducing a model task with connection web models that combine system dynamic causality, soft systems thinking, and spatial dimensions in a new way. The model task was developed and tested empirically in two upper secondary schools in Sweden. Research data consist of interviews and recordings of the students’ work with connection web models as a way of exploring complex issues. Findings from the study are presented in four peer-reviewed articles that together answer the two research questions: i) what does it mean to become system geographically knowledgeable when managing complex geographical issues? and ii) how can Geography teaching be designed to develop students’ system geographical knowing? Article I proposes a subject didactic model where the systems concept and other geographical concepts were used as organising tools to design Geography teaching. The model was developed in collaboration with Geography teachers and was used for designing the teaching interventions in the present study. Article II contributes findings from a series of lessons where the connection web model was introduced and presents four qualitatively different aspects of knowing that are critical for students to be able to use the model. For instance, being able to discern different causal characters of connections, to use place and scale as analytical tools, and to interpret the holistic pattern of interwoven connections. Article III analyses three different teaching designs and presents four design principles that teachers can use to support the development of the students’ system geographical knowing and overcome challenges that have been identified. Article IV presents findings about how the students experience the phenomenon of using the connection web models as a way of managing complex issues. Three different ways of experiencing the phenomenon are presented as well as critical aspects that students need to experience to qualify their knowing. This doctoral thesis broadens the view on what systems thinking can mean in the integrated and spatial school subject of Geography and contributes didactic models for teachers and researchers to use to develop the students’ knowing. The study argues that system geographical knowing is relevant for students to better understand complex issues concerning system changes. Finally, it is argued that connection web models have the potential to function as learning models if the model work is considered as a long-term process.
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24.
  • Dessen Jankell, Lotta, 1970-, et al. (författare)
  • System Geographical Webbing as an Object of Knowing to Analyze Sustainability Issues in Geography
  • 2022
  • Ingår i: Journal of Geography education. - 2198-4298. ; 50:3, s. 119-140
  • Tidskriftsartikel (refereegranskat)abstract
    • This article explores system geographical webbing, i.e., to use a specific connection web to analyze sustainability issues, as an object of knowing in upper secondary Geography teaching. A model task was developed based on systems principles and geographical concepts. Empirical data consists of teaching interventions aimed at encouraging students to perform webbing actions and to construct geographical relationships of sustainability issues. The article describes aspects of the geographical knowing needed for using a connection web and its embedded tools to explore sus- tainability issues. Finally, the article suggests avenues for teachers to support system geographical knowing development. 
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25.
  • Eklund, Malin B., et al. (författare)
  • Differential effects of repeated long and brief maternal separation on behaviour and neuroendocrine parameters in Wistar dams
  • 2009
  • Ingår i: Behavioural Brain Research. - : Elsevier. - 0166-4328 .- 1872-7549. ; 203:1, s. 69-75
  • Tidskriftsartikel (refereegranskat)abstract
    • Repeated, prolonged maternal separation has been suggested to model the development of a depression-like syndrome in rats. The long separations from the pups have been proposed to be stressful for the dams, which in turn could mediate the changes seen in adult offspring. In the present study we investigated whether prolonged maternal separation really is stressful for rat dams by studying parameters known to be affected by long-term stress such as spontaneous motor activity, anxiety-like behaviour, adrenal gland weight and plasma corticosterone levels. Dams were separated from their litter for either 4 h (MS240) or 15 min (MS15) on eight random days during postnatal day 1–14, or left undisturbed (animal facility reared, AFR). After weaning MS240 dams showed decreased peripheral activity and habituated slower in horizontal activity. On the contrary, MS15 dams showed more peripheral activity and less rearing activity compared to both AFR and MS240 dams when habituated to the testing apparatus, suggesting that MS15 dams are more anxious. The adrenal glands from MS15 dams weighed significantly less and plasma corticosterone levels were significantly higher compared to AFR and MS240 dams. These results suggest that repeated brief maternal separations from pups could be stressful for rat mothers, whereas prolonged separations are not. Since these results are in contrast to the current notion that the short separation procedure may be considered as a safe milieu, whereas the prolonged separations have been suggested to be stressful for both dams and pups, further studies in this field are warranted.
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26.
  • Engwall, Marie, et al. (författare)
  • Lighting, sleep and circadian rhythm: An intervention study in the intensive care unit
  • 2015
  • Ingår i: Intensive and Critical Care Nursing. - : Elsevier BV. - 0964-3397 .- 1532-4036. ; 31:6, s. 325-335
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients in an intensive care unit (ICU) may risk disruption of their circadian rhythm. In an intervention research project a cycled lighting system was set up in an ICU room to support patients' circadian rhythm. Part I aimed to compare experiences of the lighting environment in two rooms with different lighting environments by lighting experiences questionnaire. The results indicated differences in advantage for the patients in the intervention room (n=48), in perception of daytime brightness (p =0.004). In nighttime, greater lighting variation (p =0.005) was found in the ordinary room (n = 52). Part II aimed to describe experiences of lighting in the room equipped with the cycled lighting environment. Patients (n=19) were interviewed and the results were presented in categories: "A dynamic lighting environment", "Impact of lighting on patients' steep", The impact of lighting/lights on circadian rhythm" and The Lighting calms". Most had experiences from sleep disorders and half had nightmares/sights and circadian rhythm disruption. Nearly all were pleased with the cycled lighting environment, which together with daylight supported their circadian rhythm. In night's actual lighting levels helped patients and staff to connect which engendered feelings of calm. (C) 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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27.
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28.
  • Eriksson, Mats, et al. (författare)
  • Water, Forests, People: The Swedish Experience in Building Resilient Landscapes
  • 2018
  • Ingår i: Environmental Management. - : Springer Science and Business Media LLC. - 0364-152X .- 1432-1009. ; 62:1, s. 45-57
  • Tidskriftsartikel (refereegranskat)abstract
    • A growing world population and rapid expansion of cities increase the pressure on basic resources such as water, food and energy. To safeguard the provision of these resources, restoration and sustainable management of landscapes is pivotal, including sustainable forest and water management. Sustainable forest management includes forest conservation, restoration, forestry and agroforestry practices. Interlinkages between forests and water are fundamental to moderate water budgets, stabilize runoff, reduce erosion and improve biodiversity and water quality. Sweden has gained substantial experience in sustainable forest management in the past century. Through significant restoration efforts, a largely depleted Swedish forest has transformed into a well-managed production forest within a century, leading to sustainable economic growth through the provision of forest products. More recently, ecosystem services are also included in management decisions. Such a transformation depends on broad stakeholder dialog, combined with an enabling institutional and policy environment. Based on seminars and workshops with a wide range of key stakeholders managing Sweden’s forests and waters, this article draws lessons from the history of forest management in Sweden. These lessons are particularly relevant for countries in the Global South that currently experience similar challenges in forest and landscape management. The authors argue that an integrated landscape approach involving a broad array of sectors and stakeholders is needed to achieve sustainable forest and water management. Sustainable landscape management—integrating water, agriculture and forests—is imperative to achieving resilient socio-economic systems and landscapes.
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29.
  • Fagerlind Ståhl, Anna-Carin, 1982- (författare)
  • Live long and prosper : Health-promoting conditions at work
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aim of this thesis is to contribute with knowledge concerning health-promoting conditions at work, and to investigate how individual, workplace and organisational conditions are interrelated. In the thesis, work-related flow, i.e. an experience of motivation, absorption and work enjoyment, is used as a holistic notion of occupational health. In Paper I, work-related flow is investigated in relation to decision latitude, social capital and an innovative learning climate at work. Paper II investigates whether the use of tools inspired by lean production, such as standardisation and value stream mapping, is positively associated with conditions for innovative learning in organisations. The aim of Paper III is to identify conditions for health and performance in organisation and at work; further, to investigate the association between work-related flow and performance. Paper IV reports on a longitudinal investigation of workrelated flow in relation to lean tool use and conditions at the workplace. The empirical material is based on data from 10 organisations, including 4442 employees. Papers I-III are cross-sectional, whereas Paper IV is longitudinal. Papers II-IV utilise multilevel analyses.The results show that decision latitude, social capital and an innovative learning climate are associated with an increase in work-related flow (Papers I, III & IV), and with performance (Paper III). Individuals’ decision latitude enables an increased benefit from the social capital and innovative learning climate at work (Paper I). The effect of tools inspired by lean production on work-related flow (Papers III & IV), and on conditions for innovative learning (Paper II) differs, depending on which tools are used, and on workplace conditions. These tools enable innovative learning mainly where decision latitude is low (Paper II), and it is primarily the lean tool value stream mapping which has the potential to create an arena for innovative learning (Paper II) and work-related flow (Paper IV).It is concluded that the individual is embedded in a social work context that has the potential to strengthen the ability to act with motivation, absorption and enjoyment. In order to utilise collective healthpromoting conditions at work, individuals need to have authority to make their own decisions and use their skills. The effect of tools inspired by lean production depends on the specific tools that are used, and on individuals’ decision latitude at work. Their potential to enable innovative learning is most evident for employees who  have few opportunities for autonomous decision-making and skill use in their work. For those with a high degree of decision latitude, the use of lean tools has a smaller effect. Work-related flow may in itself serve as a resource that improves performance and increases engagement in health-promoting work conditions. In order to promote health as well as performance, work needsto be organised so that employees have opportunities to decide over their own work, and utilise their skills, individually and collectively within the workgroup.
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30.
  • Fröbert, Ole, et al. (författare)
  • Thrombus Aspiration during ST-Segment Elevation Myocardial Infarction
  • 2013
  • Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 369:17, s. 1587-1597
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe clinical effect of routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is uncertain. We aimed to evaluate whether thrombus aspiration reduces mortality. MethodsWe conducted a multicenter, prospective, randomized, controlled, open-label clinical trial, with enrollment of patients from the national comprehensive Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and end points evaluated through national registries. A total of 7244 patients with STEMI undergoing PCI were randomly assigned to manual thrombus aspiration followed by PCI or to PCI only. The primary end point was all-cause mortality at 30 days. ResultsNo patients were lost to follow-up. Death from any cause occurred in 2.8% of the patients in the thrombus-aspiration group (103 of 3621), as compared with 3.0% in the PCI-only group (110 of 3623) (hazard ratio, 0.94; 95% confidence interval [CI], 0.72 to 1.22; P=0.63). The rates of hospitalization for recurrent myocardial infarction at 30 days were 0.5% and 0.9% in the two groups, respectively (hazard ratio, 0.61; 95% CI, 0.34 to 1.07; P=0.09), and the rates of stent thrombosis were 0.2% and 0.5%, respectively (hazard ratio, 0.47; 95% CI, 0.20 to 1.02; P=0.06). There were no significant differences between the groups with respect to the rate of stroke or neurologic complications at the time of discharge (P=0.87). The results were consistent across all major prespecified subgroups, including subgroups defined according to thrombus burden and coronary flow before PCI. ConclusionsRoutine thrombus aspiration before PCI as compared with PCI alone did not reduce 30-day mortality among patients with STEMI. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01093404.)
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31.
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32.
  • Glader, Eva-Lotta, 1972-, et al. (författare)
  • Differences in Long-Term Outcome Between Patients Treated in Stroke Units and in General Wards : A 2-Year Follow-Up of Stroke Patients in Sweden
  • 2001
  • Ingår i: Stroke. - : American Heart Association, Inc.. - 0039-2499 .- 1524-4628. ; 32, s. 2124-2130
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose— The long-term beneficial effects of stroke unit care have been proved in several randomized trials. However, there is a question of large-scale applicability in routine clinical practice of interventions used by dedicated investigators in small randomized trials. The objective of this study was to compare, 21/2 years after stroke, patients who had been treated in stroke units and those treated in general wards in routine clinical practice.Methods— This is a prospective cohort study based on 8194 patients who were included, during the first 6 months in 1997, in Riks-Stroke, the Swedish National Register for quality assessment of acute stroke. Two years after the event, 5189 patients were still alive and 5104 were followed up with a postal questionnaire to which 4038 responded.Results— Among the group of patients who were independent in activities of daily living (ADL) functions before the stroke, patients who were treated in stroke units were less often dependent in ADL functions, after adjustment for case mix (OR, 0.79; CI, 0.66 to 0.94). If they also lived at home before the stroke, then they had a lower case-fatality rate 2 years after the stroke (OR, 0.81; CI, 0.72 to 0.92).Conclusions— Long-term beneficial effects of treatment in stroke units were shown for patients who were independent in ADL functions before the stroke. No benefits were shown for patients who were dependent on help for primary ADL before the stroke. Further studies on this group of patients with more detailed outcome measures are needed.
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33.
  • Gunnarsson, Lotta, et al. (författare)
  • LVU-utredningar : En kritisk granskning
  • 1993
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Tolv stycken barnavårdsutredningar granskades gällande fullföljande av aktuella lagars intentioner och gällande saklighetsaspekter. Granskningen påvisar allvarliga brister vad gäller saklighet, beaktande av klientperspektiv och resursanalyser. 
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34.
  • Hallberg, Sven-Erik, et al. (författare)
  • Anti-Skid Treatment Tests with Glucose, Fructose and Unrefined Sugar
  • 2007
  • Konferensbidrag (refereegranskat)abstract
    • Over the past ten years, salt consumption for de-icing treatment on Swedish roads has been halved from approximately 400,000 tons to some 200,000 tons per year. This is largely a result of preventive measures with salt solution, which entails significantly smaller salt doses than in the case of dry and moistened salt. The purpose of the investigation has been to conduct tests with a salt solution in combination with glucose/fructose/refined sugar in order to determine whether a certain amount of the salt solution can be replaced by a product containing these substances and the kind of technical and environmental effects the mixture would have. The introductory trials, which were performed on an airport landing strip 2004/2005 gave experience of value, regarding friction coefficients etc, to continued testing. Field tests have been carried out the winter season 2005/2006. The fact that salt will continue to play an important role in anti-freeze treatment is borne out by the testing. The investigation has shown that it is possible to use a mixture of the salt solution that is today used for anti-freeze treatment together with a glucose/fructose product and maintain safety friction conditions. Exactly how large the sugar solution is and its concentration should be further studied through continued airfield trials and as well as on a section of road used by traffic. The results from the recent season as using mixtures of 75% salt and 25% sugar as well as trials on 50/50 base, looks promising. The sugar part of the solution can not melt ice but delay freezing. The product should be looked upon as a complement to salt as it leads to a lower freezing-point of the solution. Friction measurements Cost The analysis does not contain any form of financial evaluation in year one as to the cost of the solution or the value of reduced salt attack on the vehicle fleet. Since the mixtures have been produced manually and on a small scale, practical handling of the mixtures on a larger scale is included in the investigation in the winter season 2005/2006. The products environmental impact on corrosion, concrete, animal life and plant life have been studied. Oxygen is consumed in the breakdown of glucose/fructose/unrefined sugar. The breaking down of glucose/fructose/unrifined sugar by micro-organisms is influenced by the presence of toxic substances such as metals and salts and should be studied both in the field and in the laboratory. Furthermore, the oxygen consumption in recipients should be studied.
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35.
  • Hansen-Axelsson, Helen, et al. (författare)
  • Breakeven prices for recording of indicator traits to reduce the environmental impact of milk production
  • 2015
  • Ingår i: Journal of Animal Breeding and Genetics. - : Wiley. - 0931-2668 .- 1439-0388. ; 132, s. 30-41
  • Tidskriftsartikel (refereegranskat)abstract
    • A breeding scheme using genomic selection and an indicator trait for environmental impact (EI) was studied to find the most effective recording strategy in terms of annual monetary genetic gain and breakeven price for the recording of indicator traits. The breakeven price shows the investment space for developing a recording system for an indicator trait. The breeding goal consisted of three traits - milk production, functional trait and environmental impact - with economic values of Euro83, Euro82 and Euro-83, respectively. The first scenario included only breeding goal traits and no indicator traits (NoIT). The other scenarios included all three breeding goal traits and one indicator trait (IT) for EI. The indicator traits were recorded on a large scale (stayability after first lactation and stature), medium scale (live weight and greenhouse gases (GHG) measured in the breath of the cow during milking) or small scale (residual feed intake and total enteric methane measured in a respiration chamber). In the scenario with stayability, the genetic gain in EI was over 11% higher than it was in NoIT. The breakeven price of recording stayability was Euro8 per record. Stayability is easy to record in the national milk recording system, and its use as an indicator trait for EI would not generate any additional recording costs. Therefore, stayability would be a good indicator trait to use to mitigate EI. The highest genetic gain in EI (23% higher compared to NoIT) was achieved when the GHG measured in the breath of the cow was used as indicator trait. The breakeven price for this indicator trait was Euro29 per record in the reference population. Ideally the recording of a specific indicator trait for EI would take place when: (i) the genetic correlation between the IT and EI is high; and (ii) the number of phenotypic records for the indicator trait is high enough to achieve a moderately high reliability of direct genomic values.
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36.
  • Harbst, Katja, et al. (författare)
  • Molecular profiling reveals low- and high-grade forms of primary melanoma.
  • 2012
  • Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1557-3265. ; 18:15, s. 4026-4036
  • Tidskriftsartikel (refereegranskat)abstract
    • For primary melanomas, tumor thickness, mitotic rate, and ulceration are well-laid cornerstones of prognostication. However, a molecular exposition of melanoma aggressiveness is critically missing. We recently uncovered a four-class structure in metastatic melanoma, which predicts outcome and informs biology. This raises the possibility that a molecular structure exists even in the early stages of melanoma and that molecular determinants could underlie histophenotype and eventual patient outcome.We subjected 223 archival primary melanomas to a horizontally integrated analysis of RNA expression, oncogenic mutations at 238 lesions, histomorphometry, and survival data.Our previously described four-class structure that was elucidated in metastatic lesions was evident within the expression space of primary melanomas. Because these subclasses converged into two larger prognostic and phenotypic groups, we used the metastatic lesions to develop a binary subtype-based signature capable of distinguishing between "high" and "low" grade forms of the disease. The two-grade signature was subsequently applied to the primary melanomas. Compared with low-grade tumors, high-grade primary melanomas were significantly associated with increased tumor thickness, mitotic rate, ulceration (all P < 0.01), and poorer relapse-free (HR = 4.94; 95% CI, 2.84-8.59), and overall (HR = 3.66; 95% CI, 2.40-5.58) survival. High-grade melanomas exhibited elevated levels of proliferation and BRCA1/DNA damage signaling genes, whereas low-grade lesions harbored higher expression of immune genes. Importantly, the molecular-grade signature was validated in two external gene expression data sets.We provide evidence for a molecular organization within melanomas, which is preserved across all stages of disease.
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37.
  • Hasselgren, Caroline, 1987, et al. (författare)
  • Sex differences in dementia: on the potentially mediating effects of educational attainment and experiences of psychological distress
  • 2020
  • Ingår i: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Old-age dementias are known to disproportionally affect women as well as individuals with low educational attainment. The higher lifetime risk of dementia among women is usually attributed to their longer life expectancy. However, the impact of sex, and subsequent gender inequity, is likely to be more multifaceted than this explanation implies. Not least because of historical inequities in access to education between the sexes and the gender and socio-economic gradients in risk factors such as stress, depression and social isolation. Consequently, the present study sought to test whether differences in educational attainment and experiences of general psychological distress mediate the association between female sex and dementia. Methods: The study utilizes data obtained through the Gothenburg H70 Birth Cohort Study and the Prospective Populations Study on Women (n = 892). Data were analysed using Confirmatory Factor Analysis (CFA) and Structural Equation Modelling (SEM) with Weighted Least Squares Means and Variance adjusted (WLSMV) estimation. General psychological distress was indicated by a latent variable and constructed from five manifest items (previous depression, stress, self-esteem, chronic loneliness and satisfaction with social situation) that were all measured at baseline. Results: While the results could not corroborate that education directly mediates the effect of sex on dementia, level of distress was predicted by both female sex (0.607, p < .001) and education (- 0.166, p < .01) and, in turn, shown to be significantly associated with dementia (0.167, p < .05), also after controlling for confounders. When time from baseline to diagnosis was increased through sequential exclusion of dementia cases, the effect of distress on dementia was no longer significant. Conclusion: The overall findings suggest that social (dis) advantage predicts general psychological distress, which thereby constitutes a potential, and rarely acknowledged, pathway between female sex, education, and dementia. They further underline the importance of attending to both education and distress as 'gendered' phenomena when considering the nature of their associations with dementia. However, the possibility of reverse causality bias must be acknowledged and the need for longitudinal studies with longer follow-up stressed.
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38.
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39.
  • Håkansson, Gisela, et al. (författare)
  • Hypoxia-inducible factor and vascular endothelial growth factor in the neuroretina and retinal blood vessels after retinal ischemia
  • 2010
  • Ingår i: Journal of Ocular Biology, Diseases, and Informatics. - : Springer Science and Business Media LLC. - 1936-8445. ; 3:1, s. 20-29
  • Tidskriftsartikel (refereegranskat)abstract
    • Retinal ischemia arises from circulatory failure. As the retinal blood vessels are key organs in circulatory failure, our aim was to study the retinal vasculature separately from the neuroretina to elucidate the role of hypoxia-inducible factor (HIF) 1α and 1β and vascular endothelial growth factor (VEGF) in retinal ischemia. Retinal ischemia was induced in porcine eyes by applying an intraocular pressure, followed by 12 h of reperfusion. HIF-1α mRNA expression was not affected by ischemia, while immunofluorescence staining was higher after ischemia in the neuroretina. HIF-1β immu-noreactivity and mRNA expression were unaffected. VEGF protein levels in the vitreous humor and VEGF staining in the neuroretina were more pronounced in eyes subjected to ischemia than in the sham eyes. VEGF may be activated downstream of HIF-1 and is known to stimulate retinal neovascularization, which causes sight-threatening complications. These results emphasize the need for pharmacological treatment to block the HIF and VEGF signaling pathways in retinal ischemia.
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42.
  • Jansson, Desirée, et al. (författare)
  • Intestinal spirochaetes (genus Brachyspira) colonise wild birds in the southern Atlantic region and Antarctica
  • 2015
  • Ingår i: Infection Ecology & Epidemiology. - : Informa UK Limited. - 2000-8686. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: The genus Brachyspira contains well-known enteric pathogens of veterinary significance, suggested agents of colonic disease in humans, and one potentially zoonotic agent. There are recent studies showing that Brachyspira are more widespread in the wildlife community than previously thought. There are no records of this genus in wildlife from the southern Atlantic region and Antarctica. Our aim was therefore, to determine whether intestinal spirochaetes of genus Brachyspira colonise marine and coastal birds in this region.METHOD: Faecal samples were collected from marine and coastal birds in the southern Atlantic region, including sub-Antarctic islands and Antarctica, in 2002, 2009, and 2012, with the aim to isolate and characterise zoonotic agents. In total, 205 samples from 11 bird species were selectively cultured for intestinal spirochaetes of genus Brachyspira. To identify isolates to species level, they were subjected to phenotyping, species-specific polymerase chain reactions, sequencing of partial 16S rRNA, NADH oxidase (nox), and tlyA genes, and phylogenetic analysis. Antimicrobial susceptibility tests were performed.RESULTS: Fourteen unique strains were obtained from 10 birds of three species: four snowy sheathbills (Chionis albus), three kelp geese (Chloephaga hybrida subsp. malvinarum), and three brown skua (Stercorarius antarcticus subsp. lonnbergi) sampled on the Falkland Islands, Tierra del Fuego in Argentina, South Georgia, South Shetland Islands, and the Antarctic Peninsula. Five Brachyspira strains were closely related to potentially enteropathogenic Brachyspira sp. of chickens: B. intermedia (n=2, from snowy sheathbills), and B. alvinipulli (n=3, from a kelp goose and two snowy sheathbills). Three strains from kelp geese were most similar to the presumed non-pathogenic species 'B. pulli' and B. murdochii, whereas the remaining six strains could not be attributed to currently known species. No isolates related to human strains were found. None of the tested strains showed decreased susceptibility to tiamulin, valnemulin, doxycycline, tylvalosin, lincomycin, or tylosin.CONCLUSIONS: This is the first report of intestinal spirochaetes from this region. Despite limitations of current diagnostic methods, our results, together with earlier studies, show that Brachyspira spp., including potentially pathogenic strains, occur globally among free-living avian hosts, and that this genus encompasses a higher degree of biodiversity than previously recognised.
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43.
  • Joensuu, Heikki, et al. (författare)
  • Effect of Adjuvant Trastuzumab for a Duration of 9 Weeks vs 1 Year With Concomitant Chemotherapy for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer The SOLD Randomized Clinical Trial
  • 2018
  • Ingår i: JAMA Oncology. - : AMER MEDICAL ASSOC. - 2374-2437 .- 2374-2445. ; 4:9, s. 1199-1206
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Trastuzumab plus chemotherapy is the standard adjuvant treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. While the standard duration of trastuzumab treatment is 12 months, the benefits and harms of trastuzumab continued beyond the chemotherapy are unclear.Objective: To evaluate the efficacy and safety of adjuvant trastuzumab continued beyond chemotherapy in women treated with up-front chemotherapy containing a taxane and trastuzumab.Design, Setting, and Participants: Open-label, randomized (1:1) clinical trial including women with HER2-positive breast cancer. Chemotherapy was identical in the 2 groups, consisting of 3 cycles of 3-weekly docetaxel (either 80 or 100 mg/m2) plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide. Thereafter, no trastuzumab was administered in the 9-week group, whereas controls received trastuzumab to complete 1 year of administration. Disease-free survival (DFS) was compared between the groups using a Cox model and the noninferiority approach. The estimated sample size was 2168 patients (1-sided testing, with a relative noninferiority margin of 1.3). From January 3, 2008, to December 16, 2014, 2176 patients were accrued from 7 countries.Intervention: Docetaxel plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide in both groups. Controls continued trastuzumab to 1 year.Main Outcomes and Measures: The primary objective was DFS; secondary objectives included distant disease–free survival, overall survival, cardiac DFS, and safety.Results: In the 2174 women analyzed, median age was 56 (interquartile range [IQR], 48-64) years. The median follow-up was 5.2 (IQR, 3.8-6.7) years. Noninferiority of the 9-week treatment could not be demonstrated for DFS (hazard ratio, 1.39; 2-sided 90% CI, 1.12-1.72). Distant disease–free survival and overall survival did not differ substantially between the groups. Thirty-six (3%) and 21 (2%) patients in the 1-year and the 9-week groups, respectively, had cardiac failure; the left ventricle ejection fraction was better maintained in the 9-week group. An interaction was detected between the docetaxel dose and DFS; patients in the 9-week group treated with 80 mg/m2 had inferior and those treated with 100 mg/m2 had similar DFS as patients in the 1-year group.Conclusions and Relevance: Nine weeks of trastuzumab was not noninferior to 1 year of trastuzumab when given with similar chemotherapy. Cardiac safety was better in the 9-week group. The docetaxel dosing with trastuzumab requires further study.Trial Registration: ClinicalTrials.gov Identifier: NCT00593697
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44.
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45.
  • Johansson Capusan, Andrea, MD PhD, 1970-, et al. (författare)
  • Den mörka sidan – ADHD vanligt vid substansbruk och kriminalitet : [The dark side of ADHD - comorbidity with substance use disorder and criminality - an overview]
  • 2022
  • Ingår i: Läkartidningen. - : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 119
  • Forskningsöversikt (refereegranskat)abstract
    • ADHD frequently co-occurs with substance use disorder (SUD) and is also common in prison populations. Screening and structured diagnosis should therefore be made available to treatment seeking SUD patients as well as to prison inmates. Multimodal, integrated treatment, including appropriate pharmacological and psychosocial therapies, is recommended for both ADHD and SUD. Long-acting stimulants with lower misuse potential are first line treatment for ADHD, with research indicating that somewhat higher stimulant doses could be necessary in this population. Increased frequency of underlying cardiovascular conditions, as well as increased risks for medication misuse in SUD populations, warrant careful treatment monitoring. There is no evidence suggesting that stimulant treatment increases risk for SUD. Given its high prevalence in prison settings, diagnosis of and integrated pharmacological and psychosocial treatment  for ADHD may decrease SUD relapse and criminality in those incarcerated.
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46.
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47.
  • Johansson, Håkan, 1972-, et al. (författare)
  • Characterization of Campylobacter spp. isolated from wild birds in the Antarctic and Sub-Antarctic
  • 2018
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 13:11
  • Tidskriftsartikel (refereegranskat)abstract
    • A lack of knowledge of naturally occurring pathogens is limiting our ability to use the Antarctic to study the impact human-mediated introduction of infectious microorganisms have on this relatively uncontaminated environment. As no large-scale coordinated effort to remedy this lack of knowledge has taken place, we rely on smaller targeted efforts to both study present microorganisms and monitor the environment for introductions. In one such effort, we isolated Campylobacter species from fecal samples collected from wild birds in the Antarctic Peninsula and the sub-Antarctic island of South Georgia. Indeed, in South Georgia, we found Campylobacter lari and the closely related Campylobacter peloridis, but also distantly related human-associated multilocus sequence types of Campylobacter jejuni. In contrast, in the Antarctic Peninsula, we found C. tart and two closely related species, Campylobacter subantarcticus and Campylobacter volucris, but no signs of human introduction. In fact, our finding of human-associated sequence types of C. jejuni in South Georgia, but not in the Antarctic Peninsula, suggests that efforts to limit the spread of infectious microorganisms to the Antarctic have so far been successful in preventing the introduction of C. jejuni. However, we do not know how it came to South Georgia and whether the same mode of introduction could spread it from there to the Antarctic Peninsula.
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48.
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49.
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50.
  • Johansson, Lotta, 1965, et al. (författare)
  • Evaluation of a sound environment intervention in an ICU : A feasibility study
  • 2018
  • Ingår i: Australian Critical Care. - Amsterdam : Elsevier. - 1036-7314 .- 1878-1721. ; 31:2, s. 59-70
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Currently, it is well known that the sound environment in intensive care units (ICU) is substandard. Therefore, there is a need of interventions investigating possible improvements. Unfortunately, there are many challenges to consider in the design and performance of clinical intervention studies including sound measurements and clinical outcomes.Objectives: (1) explore whether it is possible to implement a full-scale intervention study in the ICU concerning sound levels and their impact on the development of ICU delirium; (2) discuss methodological challenges and solutions for the forthcoming study; (3) conduct an analysis of the presence of ICU delirium in the study group; and (4) describe the sound pattern in the intervention rooms.Methods: A quasi-randomized clinical trial design was chosen. The intervention consisted of a refurbished two-bed ICU patient room (experimental) with a new suspended wall-to-wall ceiling and a low frequency absorber. An identical two-bed room (control) remained unchanged.Inclusion criteria: Patients >18 years old with ICU lengths of stay (LoS) >48. h. The final study group consisted of 31 patients: six from the rebuilt experimental room and 25 from the control room. Methodological problems and possible solutions were continuously identified and documented.Results: Undertaking a full-scale intervention study with continuous measurements of acoustic data in an ICU is possible. However, this feasibility study demonstrated some aspects to consider before start. The randomization process and the sound measurement procedure must be developed. Furthermore, proper education and training are needed for determining ICU delirium.Conclusion: This study raises a number of points that may be helpful for future complex interventions in an ICU. For a full-scale study to be completed a continuously updated cost calculation is necessary. Furthermore, representatives from the clinic need to be involved in all stages during the project. 
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