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Sökning: WFRF:(Jansson Caroline)

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1.
  • Berndt, Sonja I., et al. (författare)
  • Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
  • Tidskriftsartikel (refereegranskat)abstract
    • Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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2.
  • Clason, Caroline C., et al. (författare)
  • Dye tracing to determine flow properties of hydrocarbon-polluted Rabots glaciar, Kebnekaise, Sweden
  • 2015
  • Ingår i: Hydrology and Earth System Sciences. - : Copernicus GmbH. - 1027-5606 .- 1607-7938. ; 19:6, s. 2701-2715
  • Tidskriftsartikel (refereegranskat)abstract
    • Over 11 000 L of kerosene was deposited on the surface of Rabots glaciar on the Kebnekaise Massif, northern Sweden, following the crash of a Royal Norwegian Air Force aircraft in March 2012. An environmental monitoring programme was subsequently commissioned, including a series of dye tracing experiments during the 2013 melt season, conducted to investigate the transport of pollutants through the glacier hydrological system. This experimental set-up provided a basis from which we could gain new insight into the internal hydrological system of Rabots glaciar. Results of dye tracing experiments reveal a degree of homogeneity in the topology of the drainage system throughout July and August, with an increase in efficiency as the season progresses, as reflected by decreasing temporary storage and dispersivity. Early onset of melting likely led to formation of an efficient, discrete drainage system early in the melt season, subject to decreasing sinuosity and braiding as the season progressed. Four distinct meltwater flow regimes are identified to summarize the temporal and spatial evolution of the system. Analysis of turbidity-discharge hysteresis further supports the formation of discrete, efficient drainage, with clockwise diurnal hysteresis suggesting easy mobilization of readily available sediments in channels. Dye injection immediately downstream of the pollution source zone reveals prolonged storage of dye followed by fast, efficient release. Twinned with a low dye recovery, and supported by sporadic detection of hydrocarbons in the proglacial river, we suggest that meltwater, and thus pollutants in solution, may be released periodically through an efficient, and likely pressurized, hydrological system within the upper reaches of the glacier.
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3.
  • Heid, Iris M, et al. (författare)
  • Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
  • Tidskriftsartikel (refereegranskat)abstract
    • Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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4.
  • Kilpeläinen, Tuomas O, et al. (författare)
  • Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
  • 2011
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:8, s. 753-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
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5.
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6.
  • Speliotes, Elizabeth K., et al. (författare)
  • Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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7.
  • Ahl, Caroline, et al. (författare)
  • Making up one's mind : patients' experiences of calling an ambulance
  • 2006
  • Ingår i: Accident and Emergency Nursing. - : Elsevier. - 0965-2302 .- 1532-9267 .- 1755-599X .- 1878-013X. ; 14:1, s. 11-19
  • Tidskriftsartikel (refereegranskat)abstract
    • The issue of the inappropriate use of ambulance transport and care has mainly been studied from the professionals' and caregivers' perspective, with few studies focusing on the patient and his/her experiences. To further understand whether patients use ambulance care in an inappropriate manner and, if so, why, it is important to obtain an overall picture of the patients' existential situation at the time they call an ambulance. The aim of this study was to analyse and describe patients' experiences related to the decision to call an ambulance and the wait for it to arrive. The design was explorative, and twenty informants aged between 34 and 82 years were interviewed. Qualitative content analyses were performed. The findings showed that calling for an ambulance is a major decision that is preceded by hesitation and attempts to handle the situation by oneself. Our conclusion is that the definition of inappropriate use of valuable health care resources should not be based solely on the professionals' point of view but also take account of the patients' reactions when they experience a threat to their life and health.
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8.
  • Alanärä, Anders, et al. (författare)
  • Utsättning av djur för jakt och fiske
  • 2021
  • Bok (populärvet., debatt m.m.)abstract
    • SLUs vetenskapliga råd för djurskydd har fått i uppdrag av Jordbruksverket att sammanställa aktuell forskning kring utsättning av djur för jakt och fiske samt att belysa eventuella kunskapsluckor på området. Uppdraget omfattar gräsand, rapphöna, fasan och laxfiskar. Bruket att föda upp fåglar och fiskar för utsättning i syfte att gynna jakt och fiske ifrågasätts inte sällan av etiska skäl, men den diskussionen ligger utanför fokus för denna rapport. Utsättning av fågel och fisk är en antropogen verksamhet som, till skillnad från många andra typer av mänsklig påverkan, syftar till att gynna arterna i fråga. Det kan handla om naturvårdsinsatser, att återinföra försvunna arter eller att på andra sätt berika ekosystemet, inte sällan med ökade möjligheter till jakt eller fiske som slutändamål. Ofta förbereds och åtföljs utsättningar av habitatförbättrande åtgärder som inte endast gynnar de utsatta individerna och deras artfränder, utan även har positiva konsekvenser för biologisk mångfald och ekosystemet i stort. I utarbetandet av regelverket knutet till utsättning av fågel och fisk är det viktigt att även beakta de positiva föresatserna och de konsekvenser som verksamheten kan medföra. Annars riskerar man att engagemang och incitament förloras, till men för biologisk mångfald och en rik och levande landsbygd.
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9.
  • Andersson, Hanna, et al. (författare)
  • Natur på skolgården för lärande, hälsa och hållbarhet
  • 2024. - 2024
  • Rapport (populärvet., debatt m.m.)abstract
    • Gröna och artrika utemiljöer främjar barns och ungas välbefinnande och kunskap, bådegenom hälsofördelar kopplade till biologisk mångfald och genom att skapa förutsättningarför lek och lärande om natur och miljöfrågor. Skolgården skulle kunna bidra till allt detta,men är idag i hög grad en outnyttjad plats för biologisk mångfald och klimatanpassningav städer. I denna policy brief presenteras huvudsakliga motiv och möjliga åtgärder för attutveckla gröna miljöer och biologisk mångfald på skolgårdar och förskolegårdar.
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10.
  • Andersson, Jenny, et al. (författare)
  • Absence of the Lhcb1 and Lhcb2 proteins of the light-harvesting complex of photosystem II - effects on photosynthesis, grana stacking and fitness
  • 2003
  • Ingår i: The Plant Journal. - : Wiley. - 0960-7412 .- 1365-313X. ; 35:3, s. 350-361
  • Tidskriftsartikel (refereegranskat)abstract
    • We have constructed Arabidopsis thaliana plants that are virtually devoid of the major light-harvesting complex, LHC II. This was accomplished by introducing the Lhcb2.1 coding region in the antisense orientation into the genome by Agrobacterium-mediated transformation. Lhcb1 and Lhcb2 were absent, while Lhcb3, a protein present in LHC II associated with photosystem (PS) II, was retained. Plants had a pale green appearance and showed reduced chlorophyll content and an elevated chlorophyll a/b ratio. The content of PS II reaction centres was unchanged on a leaf area basis, but there was evidence for increases in the relative levels of other light harvesting proteins, notably CP26, associated with PS II, and Lhca4, associated with PS I. Electron microscopy showed the presence of grana. Photosynthetic rates at saturating irradiance were the same in wild-type and antisense plants, but there was a 10-15% reduction in quantum yield that reflected the decrease in light absorption by the leaf. The antisense plants were not able to perform state transitions, and their capacity for non-photochemical quenching was reduced. There was no difference in growth between wild-type and antisense plants under controlled climate conditions, but the antisense plants performed worse compared to the wild type in the field, with decreases in seed production of up to 70%.
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11.
  • Askenmalm, Fredrika (författare)
  • Hur mjölk i tanken blir kronor på banken : Bondförnuftets rationalitet
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Lantbrukare har under senare år ofta hörts framföra klagomål om att den administrativa bördan blivit allt tyngre vad gäller rapportering och ansökningar som ska göras till olika myndigheter. Tidigare forskning framställer det som att den administrativa bördan skulle kunna utsträckas till att också gälla redovisning, så som bokföring, kalkylering och budgetering. Detta då det beskrivs som att lantbrukare varken förstår eller använder redovisning för att sköta sitt lantbruk. Tidigare forskning tycks dock bortse från att lantbrukare ofta tillämpar en annan form av logik än den som förutsätts gälla inom redovisningsforskning. Det verkar också förutsättas att lantbrukarna ska kunna förstå och använda den redovisningsterminologi som finns inom forskningsvärlden trots att lantbrukarna ofta saknar utbildning inom redovisning. Mot denna bakgrund undersöker denna avhandling hur lantbrukare förstår och använder redovisning.Avhandlingen bygger på det grundläggande teoretiska perspektivet att se redovisning som ett språk för att på detta sätt förklara lantbrukarnas förståelse av redovisning. Avhandlingen bygger vidare på familjeföretagsforskning, speciellt socioemotional wealth (SEW), och beslutsteori för att förklara lantbrukarnas användning av redovisningsinformation.Den empiriska studien är inspirerad av grundad teori. Det empiriska materialet utgörs främst av intervjuer med mjölkbönder i Jönköpings län. Även intervjuer med rådgivare och bankmän och vissa sekundärdata har utgjort underlag för avhandlingen.Resultatet av undersökningen visar att lantbrukare har större kunskaper vad gäller redovisning än vad tidigare forskning indikerat. Delvis kan detta förklaras av att lantbrukare använder en annan terminologi än vad som vanligtvis används inom redovisningsforskning när de beskriver redovisning. Mjölkföretag drivs vanligen som familjeföretag och denna avhandling visar på en mycket stark familjeförankring i dessa företag. Det innebär att mjölkföretag ibland (speciellt vad gäller fastigheten) prioriterar annat än finansiella mål, vilket ofta kopplas samman med en intuitiv beslutsstil. Inom redovisning förutsätts generellt att finansiella mål är eftersträvansvärda. Lantbrukarnas sätt att se på redovisning påverkar också hur den används. Även om de förstår och använder redovisning är det inte säkert att den används på det mest vinstmaximerande sättet. I stället kan SEW vara det som prioriteras. Användning av redovisning anpassas efter den situation lantbrukaren befinner sig i. Vissa delar av redovisningen ses och förstås som speglingar av verkligheten eller som framåtriktade ledtrådar. När lantbrukare förstår redovisningen på så vis, uppfattas den som användbar för beslutsfattande. Andra delar av redovisningen ses som regelföljande, eller ibland till och med som helt frikopplad från själva verksamheten. Detta gäller framför allt redovisning till Skatteverket och Jordbruksverket. Dessa redovisningar används inte för beslut, men de är ändå rationellt utformade för att uppnå bästa möjliga utfall (skatteutjämning eller jordbruksstöd).
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12.
  • Backman, Helena, et al. (författare)
  • A population-based cohort of adults with asthma: mortality and participation in a long-term follow-up
  • 2017
  • Ingår i: European Clinical Respiratory Journal. - : Informa UK Limited. - 2001-8525. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and objective: Asthma is a major public health concern. The aim of this study was to characterize a large population-based cohort of adults with asthma, and to study factors associated with all-cause mortality and non-participation in a long-term follow-up. Design: Random and stratified samples from five population-based cohorts were clinically examined during 1986-2001, and all subjects with asthma were included in the study (n = 2055, age 19-72 years, 55% women). Independent associations between different risk factors and (i) mortality and (ii) non-participation in a clinical follow-up in 2012-2014 were estimated. Results: In 1986-2001, 95% reported any wheeze and/or attacks of shortness of breath in the past 12 months, and/or asthma medication use. Over the up to 28 years of follow-up time, the cumulative mortality was 22.7%. Male gender, current smoking, and lower forced expiratory volume in 1 sec of predicted (FEV1% of predicted) were independent risk factors for mortality, while obesity was associated with non-participation in the follow-up. Older ages, ischemic heart disease, and low socioeconomic status were associated with both mortality and non-participation. Conclusions: The risk factors associated with mortality in this adult population-based asthma cohort were similar to those commonly identified in general population samples, i.e. male gender, current smoking, and lower FEV1% of predicted, while obesity was associated with non-participation in a long-term follow-up. Ischemic heart disease, low socioeconomic status, and older ages were associated with both mortality and non-participation.
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13.
  • Backman, Helena, et al. (författare)
  • Chronic airway obstruction in a population-based adult asthma cohort : Prevalence, incidence and prognostic factors
  • 2018
  • Ingår i: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 138, s. 115-122
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAsthma and COPD may overlap (ACO) but information about incidence and risk factors are lacking. This study aimed to estimate prevalence, incidence and risk factors of chronic airway obstruction (CAO) in a population-based adult asthma cohort.MethodsDuring 1986–2001 a large population-based asthma cohort was identified (n = 2055, 19-72y). Subsamples have participated in clinical follow-ups during the subsequent years. The entire cohort was invited to a clinical follow-up including interview, spirometry, and blood sampling in 2012–2014 when n = 983 subjects performed adequate spirometry. CAO was defined as post-bronchodilator FEV1/FVC<0.7.ResultsAt study entry, asthmatics with prevalent CAO (11.4%) reported more respiratory symptoms, asthma medication use, and ischemic heart disease than asthmatics without CAO (asthma only). Subjects who developed CAO during follow-up (17.6%; incidence rate of 16/1000/year) had a more rapid FEV1 decline and higher levels of neutrophils than asthma only. Smoking, older age and male sex were independently associated with increased risk for both prevalent and incident CAO, while obesity had a protective effect.ConclusionsIn this prospective adult asthma cohort, the majority did not develop CAO. Smoking, older age and male sex were risk factors for prevalent and incident CAO, similar to risk factors described for COPD in the general population.
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14.
  • Backman, Helena, et al. (författare)
  • Decreased COPD prevalence in Sweden after decades of decrease in smoking
  • 2020
  • Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 21
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundCOPD has increased in prevalence worldwide over several decades until the first decade after the millennium shift. Evidence from a few recent population studies indicate that the prevalence may be levelling or even decreasing in some areas in Europe. Since the 1970s, a substantial and ongoing decrease in smoking prevalence has been observed in several European countries including Sweden. The aim of the current study was to estimate the prevalence, characteristics and risk factors for COPD in the Swedish general population. A further aim was to estimate the prevalence trend of COPD in Northern Sweden from 1994 to 2009.MethodsTwo large random population samples were invited to spirometry with bronchodilator testing and structured interviews in 2009–2012, one in south-western and one in northern Sweden, n = 1839 participants in total. The results from northern Sweden were compared to a study performed 15 years earlier in the same area and age-span. The diagnosis of COPD required both chronic airway obstruction (CAO) and the presence of respiratory symptoms, in line with the GOLD documents since 2017. CAO was defined as post-bronchodilator FEV1/FVC < 0.70, with sensitivity analyses based on the FEV1/FVC < lower limit of normal (LLN) criterion.ResultsBased on the fixed ratio definition, the prevalence of COPD was 7.0% (men 8.3%; women 5.8%) in 2009–2012. The prevalence of moderate to severe (GOLD ≥ 2) COPD was 3.5%. The LLN based results were about 30% lower. Smoking, occupational exposures, and older age were risk factors for COPD, whereof smoking was the most dominating risk factor. In northern Sweden the prevalence of COPD, particularly moderate to severe COPD, decreased significantly from 1994 to 2009, and the decrease followed a decrease in smoking.ConclusionsThe prevalence of COPD has decreased in Sweden, and the prevalence of moderate to severe COPD was particularly low. The decrease follows a major decrease in smoking prevalence over several decades, but smoking remained the dominating risk factor for COPD.
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15.
  • Backman, Helena, et al. (författare)
  • Decreased prevalence of moderate to severe COPD over 15 years in northern Sweden
  • 2016
  • Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 114, s. 103-110
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The burden of COPD in terms of mortality, morbidity, costs and prevalence has increased worldwide. Recent results on prevalence in Western Europe are conflicting. In Sweden smoking prevalence has steadily decreased over the past 30 years. Aim: The aim was to study changes in prevalence and risk factor patterns of COPD in the same area and within the same age-span 15 years apart. Material and methods: Two population-based cross-sectional samples in ages 23-72 years participating at examinations in 1994 and 2009, respectively, were compared in terms of COPD prevalence, severity and risk factor patterns. Two different definitions of COPD were used; FEV1/FVC < LLN and FEV1/FVC < 0.7. The severity of COPD was assessed by FEV1, both as % of predicted and in relation to the LLN. Results: The prevalence of COPD decreased significantly from 9.5% to 6.3% (p = 0.030) according to the FEV1/FVC < LLN criterion, while the decrease based on the FEV1/FVC < 0.7 criterion from 10.5% to 8.5% was non-significant. The prevalence of moderate to severe COPD decreased substantially and significantly, and the risk factor pattern was altered in 2009 when, beside age and smoking, also socioeconomic status based on occupation was significantly associated with COPD. Conclusions: Changes in both prevalence and risk factor patterns of COPD were observed between surveys. Following a continuing decrease in smoking habits over several decades, a decrease in the prevalence of moderate to severe COPD was observed from 1994 to 2009 in northern Sweden.
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16.
  • Backman, Helena, et al. (författare)
  • Decreased prevalence of moderate to severe COPD over 15 years in northern Sweden
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background: The burden of COPD in terms of mortality, morbidity, costs and prevalence has increased worldwide. Recent results on prevalence in Western Europe are conflicting. In Sweden smoking prevalence has steadily decreased over the past 30 years. Aim: The aim was to study changes in prevalence and risk factor patterns of COPD in the same area and within the same age-span 15 years apart.Material and methods: Two population-based cross-sectional samples in ages 23-72 years participating at examinations in 1994 and 2009, respectively, were compared in terms of COPD prevalence, severity and risk factor patterns. Two different definitions of COPD were used; FEV1/FVC1/FVC<0.7. The severity of COPD was assessed by FEV1, both as % of predicted and in relation to the LLN.Results: The prevalence of COPD decreased significantly from 9.5% to 6.3% (p=0.030) according to the FEV1/FVC1/FVC<0.7 criterion from 10.5% to 8.5% was non-significant. The prevalence of moderate to severe COPD decreased substantially and significantly, and the risk factor pattern was altered in 2009 when, beside age and smoking, also socio-economic status based on occupation was significantly associated with COPD. Conclusions: Changes in both prevalence and risk factor patterns of COPD were observed between surveys. Following a continuing decrease in smoking habits over several decades, a decrease in the prevalence of moderate to severe COPD was observed from 1994 to 2009 in northern Sweden.
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17.
  • Backman, Helena, et al. (författare)
  • Eosinophilic inflammation and lung function decline in a long-term follow-up of a large population-based asthma cohort
  • 2018
  • Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The relationship between lung function decline and airway inflammation among asthmatics has important therapeutic implications, but has rarely been studied in large samples or in population-based asthma cohorts.A population-based adult asthma cohort (n=2055) was recruited during 1986-2001 and clinically examined including spirometry. In 2012-2014, all still eligible subjects (n=1425) were invited to a clinical follow-up including spirometry, blood sampling, and a structured interview, and n=1006 participated (55% women, mean age 59y, 32-92y). Linear regression was performed with age, sex, smoking habits, year of first examination, family history of asthma, socioeconomic status, eosinophils (EOS)>=0.3x109/L, and neutrophils (NEUT)>=5.0x109/L as independent variables and pre-bronchodilator FEV1 decline/year (ml and % of predicted [pp], respectively) as dependent. In secondary models, both ICS use at baseline and ICS use at follow-up were also included.The mean annual FEV1 decline in ml (pp) among asthmatics with EOS<0.3, 0.4>EOS>=0.3 and EOS>=0.4x109/L, respectively, was 26ml (0.03pp), 29ml (0.10pp) and 34ml (0.27pp) (p<0.001). In adjusted analyses, EOS>=0.3 was significantly associated with FEV1 decline, both in terms of ml (4ml excess annual decline vs EOS<0.3) and pp. The association between EOS and FEV1 decline in pp, but not ml, remained when additionally adjusted for ICS use. The association with NEUT>=5.0x109/L was less clear.On group level, adult asthmatics with higher levels of eosinophils in blood have a history of excess FEV1 decline compared to asthmatics with lower levels of eosinophil inflammation, independent of other factors such as ICS use.
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18.
  • Backman, Helena, et al. (författare)
  • FEV1 decline in relation to blood eosinophils and neutrophils in a population-based asthma cohort
  • 2020
  • Ingår i: World Allergy Organization Journal. - : Elsevier. - 1939-4551. ; 13:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The relationship between lung function decline and eosinophils and neutrophils has important therapeutic implications among asthmatics, but it has rarely been studied in large cohort studies.Objective: The aim is to study the relationship between blood eosinophils and neutrophils and FEV1 decline in a long-term follow-up of a population-based adult asthma cohort.Methods: In 2012-2014, an adult asthma cohort was invited to a follow-up including spirometry, blood sampling, and structured interviews, and n = 892 participated (55% women, mean age 59 y, 32-92 y). Blood eosinophils, neutrophils and FEV 1 decline were analyzed both as continuous variables and divided into categories with different cut-offs. Regression models adjusted for smoking, exposure to vapors, gas, dust, or fumes (VGDF), use of inhaled and oral corticosteroids, and other possible confounders were utilized to analyze the relationship between eosinophils and neutrophils at follow-up and FEV1 decline.Results: The mean follow-up time was 18 years, and the mean FEV 1 decline was 27 ml/year. The annual FEV1 decline was related to higher levels of both blood eosinophils and neutrophils at follow-up, but only the association with eosinophils remained when adjusted for confounders. Further, the association between FEV1 decline and eosinophils was stronger among those using ICS. With EOS <0.3 × 109/L as reference, a more rapid decline in FEV1 was independently related to EOS ≥0.4 × 109/L in adjusted analyses.Conclusions and clinical relevance: Besides emphasizing the importance of smoking cessation and reduction of other harmful exposures, our real-world results indicate that there is an independent relationship between blood eosinophils and FEV1 decline among adults with asthma.
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19.
  • Backman, Helena, et al. (författare)
  • Restrictive spirometric pattern in the general adult population: Methods of defining the condition and consequences on prevalence
  • 2016
  • Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 120, s. 116-123
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Attempts have been made to use dynamic spirometry to define restrictive lung function, but the definition of a restrictive spirometric pattern (RSP) varies between studies such as BOLD and NHANES. The aim of this study was to estimate the prevalence and risk factors of RSP among adults in northern Sweden based on different definitions. Methods In 2008–2009 a general population sample aged 21–86y within the obstructive lung disease in northern Sweden (OLIN) studies was examined by structured interview and spirometry, and 726 subjects participated (71% of invited). The prevalence of RSP was calculated according to three different definitions based on pre-as well as post-bronchodilator spirometry: 1) FVC<80% & FEV1/FVC>0.7 2) FVC<80% & FEV1/FVC>LLN 3) FVCLLN Results The three definitions yielded RSP prevalence estimates of 10.5%, 11.2% and 9.4% respectively, when based on pre-bronchodilator values. The prevalence was lower when based on post-bronchodilator values, i.e. 7.3%, 7.9% and 6.6%. According to definition 1 and 2, the RSP prevalence increased by age, but not according to definition 3. The overlap between the definitions was substantial. When corrected for confounding factors, manual work in industry and diabetes with obesity were independently associated with an increased risk for RSP regardless of definition. Conclusions The prevalence of RSP was 7–11%. The prevalence estimates differed more depending on the choice of pre- compared to post-bronchodilator values than on the choice of RSP definition. RSP was, regardless of definition, independently associated with manual work in industry and diabetes with obesity. © 2016 The Authors
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20.
  • Backman, Helena, et al. (författare)
  • Risk factors for severe asthma among adults with asthma
  • 2020
  • Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 56:Suppl 64
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Severe asthma is a considerable challenge for patients, health care professionals and society, but there are few long-term studies on risk factors for severe asthma.Aim: To identify baseline risk factors of severe asthma in a longitudinal adult asthma cohort study.Methods: An adult asthma cohort was identified in 1986-2001 by clinical examinations of population samples within the OLIN studies in northern Sweden. The examinations included structured interviews, spirometry with reversibility testing, skin prick testing and metacholine challenge. The cohort was followed up in 2012-2014 when n=1006 participated (mean age 59y). Adjusted Risk Ratios (RR) for baseline factors as risk factors for GINA defined severe asthma (SA) at follow-up (n=51) were estimated by Poisson regression.Results: Older age, impaired lung function, increased reversibility and hyperreactivity, asthmatic wheeze, persistent wheeze, nighttime awakenings due to respiratory symptoms, and dyspnea were significant baseline risk factors for SA. Allergic sensitization, smoking, occupational groups or BMI did not predict SA. When adjusted for age, sex and smoking, post-bronchodilator FEV1/FVC<0.7, both present at baseline (RR 4.2, 95%CI 1.8-9.9) and developed during follow-up (2.9, 1.6-5.3), increased the risk. Also FEV1<80% at baseline associated with SA (2.9, 1.6-5.2). Triggers for respiratory symptoms at baseline such as tobacco smoke (2.1, 1.2-3.7) and physical activity (3.5, 1.5-81) associated with SA at follow-up, while pollen and furry animals did not.Conclusion: Among adults with asthma, impaired lung function, wheeze, dyspnea and nighttime awakenings due to respiratory symptoms are important long-term risk factors for severe asthma.
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21.
  • Backman, Helena, et al. (författare)
  • Severe asthma : A population study perspective
  • 2019
  • Ingår i: Clinical and Experimental Allergy. - : John Wiley & Sons. - 0954-7894 .- 1365-2222. ; 49:6, s. 819-828
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundSevere asthma is a considerable challenge for patients, health care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern definitions of which none based on a population study.ObjectiveTo describe characteristics and estimate the prevalence of severe asthma in a large adult population‐based asthma cohort followed for 10‐28 years.MethodsN=1006 subjects with asthma participated in a follow‐up during 2012‐14, when 830 (mean age 59y, 56% women) still had current asthma. Severe asthma was defined according to three internationally well‐known criteria: the ATS workshop definition from 2000 used in the US Severe Asthma Research Program (SARP), the 2014 ATS/ERS Task force definition and the GINA 2017. All subjects with severe asthma according to any of these criteria were undergoing respiratory specialist care, and were also contacted by telephone to verify treatment adherence.ResultsThe prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS Taskforce), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >40% had uncontrolled asthma according to the asthma control test. Severe asthma was related to age >50 years, nasal polyposis, impaired lung function, sensitization to aspergillus, and tended to be more common in women. Further, neutrophils in blood significantly discriminated severe asthma from other asthma.Conclusions and clinical relevanceSevere asthma differed significantly from other asthma in terms of demographic, clinical and inflammatory characteristics, results suggesting possibilities for improved treatment regimens of severe asthma. The prevalence of severe asthma in this asthma cohort was 4‐6%, corresponding to approximately 0.5% of the general population.
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22.
  • Backman, Helena, et al. (författare)
  • Severe asthma among adults : Prevalence and clinical characteristics
  • 2018
  • Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Severe asthma is a considerable challenge for patients, health care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern definitions of which none based on a population study.Methods: We estimated the prevalence and studied characteristics of severe asthma in a large adult population-based asthma cohort followed for 10-28 years in northern Sweden: 1006 subjects participated in a follow-up during 2012-14, when 830 (82.5%) still had current asthma (mean age 59y, 32-92y, 56% women). Severe asthma was defined according to three internationally well-known criteria: the US SARP, ATS/ERS and GINA. All subjects with severe asthma were undergoing respiratory specialist care, and were also contacted by telephone to verify adherence to treatment.Results: The prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >40% had uncontrolled asthma and <10% had controlled asthma according to the ACT. Severe asthma was related to age >50 years, nasal polyposis, decreased FEV1, not fully reversible airway obstruction, sensitization to aspergillus, elevated neutrophils and partly to eosinophils, and tended to be more common in women.Conclusion: The prevalence of severe asthma in this asthma cohort was 4-6%, corresponding to approximately 0.5% of the population in northern Sweden. A substantial proportion of those with severe asthma had uncontrolled disease, and severe asthma differed significantly from other asthma in terms of both clinical and inflammatory characteristics.
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23.
  • Batool, Tahira, et al. (författare)
  • Upregulated BMP-Smad signaling activity in the glucuronyl C5-epimerase knock out MEF cells
  • 2019
  • Ingår i: Cellular Signalling. - : Elsevier. - 0898-6568 .- 1873-3913. ; 54, s. 122-129
  • Tidskriftsartikel (refereegranskat)abstract
    • Glucuronyl C5-epimerase (Hsepi) catalyzes the conversion of glucuronic acid to iduronic acid in the process of heparan sulfate biosynthesis. Targeted interruption of the gene, Glce,in mice resulted in neonatal lethality with varied defects in organ development. To understand the molecular mechanisms of the phenotypes, we used mouse embryonic fibroblasts (MEF) as a model to examine selected signaling pathways. Our earlier studies found reduced activities of FGF-2, GDNF, but increased activity of sonic hedgehog in the mutant cells. In this study, we focused on the bone morphogenetic protein (BMP) signaling pathway. Western blotting detected substantially elevated endogenous Smad1/5/8 phosphorylation in the Hsepi mutant (KO) MEF cells, which is reverted by re-expression of the enzyme in the KO cells. The mutant cells displayed an enhanced proliferation and elevated alkaline phosphatase activity, marking higher differentiation, when cultured in osteogenic medium. The high level of Smad1/5/8 phosphorylation was also found in primary calvarial cells isolated from the KO mice. Analysis of the genes involved in the BMP signaling pathway revealed upregulation of a number of BMP ligands, but reduced expression of several Smads and BMP antagonist (Grem1) in the KO MEF cells. The results suggest that Hsepi expression modulates BMP signaling activity, which, at least partially, is associated with defected molecular structure of heparan sulfate expressed in the cells.   
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24.
  • Bergenfelz, Caroline, et al. (författare)
  • Systemic Monocytic-MDSCs Are Generated from Monocytes and Correlate with Disease Progression in Breast Cancer Patients.
  • 2015
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Myeloid-derived suppressor cells (MDSCs) are highly immunosuppressive myeloid cells, which increase in cancer patients. The molecular mechanism behind their generation and function is unclear. Whereas granulocytic-MDSCs correlate with poor overall survival in breast cancer, the presence and relevance of monocytic-MDSCs (Mo-MDSCs) is unknown. Here we report for the first time an enrichment of functional blood Mo-MDSCs in breast cancer patients before they acquire a typical Mo-MDSC surface phenotype. A clear population of Mo-MDSCs with the typical cell surface phenotype (CD14+HLA-DRlow/-CD86low/-CD80low/-CD163low/-) increased significantly first during disease progression and correlated to metastasis to lymph nodes and visceral organs. Furthermore, monocytes, comprising the Mo-MDSC population, from patients with metastatic breast cancer resemble the reprogrammed immunosuppressive monocytes in patients with severe infections, both by their surface and functional phenotype but also at their molecular gene expression profile. Our data suggest that monitoring the Mo-MDSC levels in breast cancer patients may represent a novel and simple biomarker for assessing disease progression.
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25.
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26.
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27.
  • Crosby, Jacy, et al. (författare)
  • Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease
  • 2014
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 371:1, s. 22-31
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G -> A and IVS3+1G -> T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1x10(-20)), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8x10(-10)). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4x10(-6)). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.)
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28.
  • Ekman, Sirkka-Liisa, et al. (författare)
  • Alzheimer
  • 2011
  • Rapport (övrigt vetenskapligt/konstnärligt)
  •  
29.
  • Erzurumluoglu, A. Mesut, et al. (författare)
  • Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
  • 2020
  • Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:10, s. 2392-2409
  • Tidskriftsartikel (refereegranskat)abstract
    • Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
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30.
  • Ghanipour, Lana, et al. (författare)
  • Efficacy of hyperthermic intraperitoneal chemotherapy in colorectal cancer : A phase I and III open label randomized controlled registry-based clinical trial protocol
  • 2024
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15–30 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC.
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31.
  • Gummesson, Anders, 1973, et al. (författare)
  • Longitudinal plasma protein profiling of newly diagnosed type 2 diabetes
  • 2021
  • Ingår i: EBioMedicine. - : Elsevier B.V.. - 2352-3964. ; 63
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Comprehensive proteomics profiling may offer new insights into the dysregulated metabolic milieu of type 2 diabetes, and in the future, serve as a useful tool for personalized medicine. This calls for a better understanding of circulating protein patterns at the early stage of type 2 diabetes as well as the dynamics of protein patterns during changes in metabolic status. Methods: To elucidate the systemic alterations in early-stage diabetes and to investigate the effects on the proteome during metabolic improvement, we measured 974 circulating proteins in 52 newly diagnosed, treatment-naïve type 2 diabetes subjects at baseline and after 1 and 3 months of guideline-based diabetes treatment, while comparing their protein profiles to that of 94 subjects without diabetes. Findings: Early stage type 2 diabetes was associated with distinct protein patterns, reflecting key metabolic syndrome features including insulin resistance, adiposity, hyperglycemia and liver steatosis. The protein profiles at baseline were attenuated during guideline-based diabetes treatment and several plasma proteins associated with metformin medication independently of metabolic variables, such as circulating EPCAM. Interpretation: The results advance our knowledge about the biochemical manifestations of type 2 diabetes and suggest that comprehensive protein profiling may serve as a useful tool for metabolic phenotyping and for elucidating the biological effects of diabetes treatments. Funding: This work was supported by the Swedish Heart and Lung Foundation, the Swedish Research Council, the Erling Persson Foundation, the Knut and Alice Wallenberg Foundation, and the Swedish state under the agreement between the Swedish government and the county councils (ALF-agreement).
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32.
  • Hamacher-Barth, Evelyne, et al. (författare)
  • A method for sizing submicrometer particles in air collected on Formvar films and imaged by scanning electron microscopy
  • 2013
  • Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 6:12, s. 3459-3475
  • Tidskriftsartikel (refereegranskat)abstract
    • A method was developed to systematically investigate individual aerosol particles collected onto a polyvinyl formal (Formvar)-coated copper grid with scanning electron microscopy. At very mild conditions with a low accelerating voltage of 2 kV and Gentle Beam mode aerosol particles down to 20 nm in diameter can be observed. Subsequent processing of the images with digital image analysis provides size resolved and morphological information (elongation, circularity) on the aerosol particle population. Polystyrene nanospheres in the expected size range of the ambient aerosol particles (20–900 nm in diameter) were used to confirm the accuracy of sizing and determination of morphological parameters. The relative standard deviation of the diameters of the spheres was better than ±10% for sizes larger than 40 nm and ±18% for 21 nm particles compared to the manufacturer's certificate. Atmospheric particles were collected during an icebreaker expedition to the high Arctic (north of 80°) in the summer of 2008. Two samples collected during two different meteorological regimes were analyzed. Their size distributions were compared with simultaneously collected size distributions from a Twin Differential Mobility Particle Sizer, which confirmed that a representative fraction of the aerosol particles was imaged under the electron microscope. The size distributions obtained by scanning electron microscopy showed good agreement with the Twin Differential Mobility Sizer in the Aitken mode, whereas in the accumulation mode the size determination was critically dependent on the contrast of the aerosol with the Formvar-coated copper grid. The morphological properties (elongation, circularity) changed with the number of days the air masses spent over the pack-ice area north of 80° before the aerosol particles were collected at the position of the icebreaker and are thus an appropriate measure to characterize transformation processes of ambient aerosol particles.
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33.
  • Hamacher-Barth, Evelyne, et al. (författare)
  • Size-resolved morphological properties of the high Arctic summer aerosol during ASCOS-2008
  • 2016
  • Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 16:10, s. 6577-6593
  • Tidskriftsartikel (refereegranskat)abstract
    • The representation of aerosol properties and processes in climate models is fraught with large uncertainties. Especially at high northern latitudes a strong underprediction of aerosol concentrations and nucleation events is observed and can only be constrained by in situ observations based on the analysis of individual aerosol particles. To further reduce the uncertainties surrounding aerosol properties and their potential role as cloud condensation nuclei this study provides observational data resolved over size on morphological and chemical properties of aerosol particles collected in the summer high Arctic, north of 80A degrees aEuro-N. Aerosol particles were imaged with scanning and transmission electron microscopy and further evaluated with digital image analysis. In total, 3909 aerosol particles were imaged and categorized according to morphological similarities into three gross morphological groups: single particles, gel particles, and halo particles. Single particles were observed between 15 and 800aEuro-nm in diameter and represent the dominating type of particles (82aEuro-%). The majority of particles appeared to be marine gels with a broad Aitken mode peaking at 70aEuro-nm and accompanied by a minor fraction of ammonium (bi)sulfate with a maximum at 170aEuro-nm in number concentration. Gel particles (11aEuro-% of all particles) were observed between 45 and 800aEuro-nm with a maximum at 154aEuro-nm in diameter. Imaging with transmission electron microscopy allowed further morphological discrimination of gel particles in 'aggregate' particles, 'aggregate with film' particles, and 'mucus-like' particles. Halo particles were observed above 75aEuro-nm and appeared to be ammonium (bi)sulfate (59aEuro-% of halo particles), gel matter (19aEuro-%), or decomposed gel matter (22aEuro-%), which were internally mixed with sulfuric acid, methane sulfonic acid, or ammonium (bi)sulfate with a maximum at 161aEuro-nm in diameter. Elemental dispersive X-ray spectroscopy analysis of individual particles revealed a prevalence of the monovalent ions Na+/K+ for single particles and aggregate particles and of the divalent ions Ca2+/Mg2+ for aggregate with film particles and mucus-like particles. According to these results and other model studies, we propose a relationship between the availability of Na+/K+ and Ca2+/Mg2+ and the length of the biopolymer molecules participating in the formation of the three-dimensional gel networks.
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34.
  • Haux, Caroline, 1960- (författare)
  • Framkallning : Skrift, konsumtion och sexualitet i Karin Boyes Astarte och Henry Parlands Sönder
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis is a comparative study in two novels which both try to understand modern life. The novels were both written between 1929 and 1930 as entries for the same major Nordic novel contest – Astarte in Sweden by Karin Boye, Sönder [To Pieces ]in Finland by the Finno-swedish author Henry Parland.This analysis tries to determine what is at stake in these novels by, apart from investigating them as novels in their own right, examining the complex interaction between a specific moment in history and the representation of that moment as literary text. The novels are examined as events in a specific historical situation; that is, how they write what is contemporary into themselves, trough answering the question about the historical moment that they themselves formulate. Four issues are fundamental to the study: The function of consumption and the commodity form in the novels. The way in which these novels render sexuality and desire. How other media forms function as aesthetic technologies for the novels. Lastly, aesthetics, writing and allegory: how the novels reflect on the possibility of representing this societal moment in history.A focus in the analysis is how woman is called forth as golden statue and photography, how she by letting herself be consumed as sexual symbol elicits male speech – thereby also making the speaker into author, and man. The economic side to this is the way in which men and women take on the form of commodities amongst themselves. It is in this sexual economy that they become men and women. The transformation of the sexed object into the systematic status of a sign, signifying its value, implies the simultaneous transformation of human relations into consumer relations: You consume or get consumed.
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35.
  • Hedman, Linnea, 1979-, et al. (författare)
  • Population-based study shows that teenage girls with asthma had impaired health-related quality of life
  • 2017
  • Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 106:7, s. 1128-1135
  • Tidskriftsartikel (refereegranskat)abstract
    • AimThis study examined the health-related quality of life (HRQoL) of teenagers with and without asthma, including the impact of their sex, allergic conditions, smoking, living conditions and physical activity.MethodsThe Obstructive Lung Disease in Northern Sweden (OLIN) studies recruited a cohort of schoolchildren in 2006. The parents of all children aged seven to eight years in three municipalities were invited to complete a questionnaire and 2585 (96%) participated. The cohort was followed up at the ages of 11–12 years and 14–15 years with high participation rates. At 14–15 years, the HRQoL questionnaire KIDSCREEN-10 and Asthma Control Test were added.ResultsGirls with current asthma at 14–15 years had a lower mean HRQoL score than girls without asthma (46.4 versus 49.3, p < 0.001), but this was not seen among boys (53.8 versus 52.8, p = 0.373). Poor HRQoL was related to current asthma, uncontrolled asthma and teenage onset of asthma. It was also related to eczema, living in a single-parent household, maternal smoking, daily smoking and inversely related to physical activity.ConclusionTeenage girls with asthma had lower HRQoL than girls without asthma. Possible interventions to improve HRQoL among teenagers with asthma were identified as follows: increasing asthma control, preventing smoking and promoting physical activity.
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36.
  • Holmquist Mengelbier, Linda, et al. (författare)
  • Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer.
  • 2015
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic differences among neoplastic cells within the same tumour have been proposed to drive cancer progression and treatment failure. Whether data on intratumoral diversity can be used to predict clinical outcome remains unclear. We here address this issue by quantifying genetic intratumoral diversity in a set of chemotherapy-treated childhood tumours. By analysis of multiple tumour samples from seven patients we demonstrate intratumoral diversity in all patients analysed after chemotherapy, typically presenting as multiple clones within a single millimetre-sized tumour sample (microdiversity). We show that microdiversity often acts as the foundation for further genome evolution in metastases. In addition, we find that microdiversity predicts poor cancer-specific survival (60%; P=0.009), independent of other risk factors, in a cohort of 44 patients with chemotherapy-treated childhood kidney cancer. Survival was 100% for patients lacking microdiversity. Thus, intratumoral genetic diversity is common in childhood cancers after chemotherapy and may be an important factor behind treatment failure.
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37.
  • Holmquist Mengelbier, Linda, et al. (författare)
  • The Iroquois homeobox proteins IRX3 and IRX5 have distinct roles in Wilms tumour development and human nephrogenesis
  • 2019
  • Ingår i: Journal of Pathology. - : Wiley. - 0022-3417. ; 247:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Wilms tumour is a paediatric malignancy with features of halted kidney development. Here, we demonstrate that the Iroquois homeobox genes IRX3 and IRX5 are essential for mammalian nephrogenesis and govern the differentiation of Wilms tumour. Knock-out Irx3−/Irx5− mice showed a strongly reduced embryonic nephron formation. In human foetal kidney and Wilms tumour, IRX5 expression was already activated in early proliferative blastema, whereas IRX3 protein levels peaked at tubular differentiation. Accordingly, an orthotopic xenograft mouse model of Wilms tumour showed that IRX3−/− cells formed bulky renal tumours dominated by immature mesenchyme and active canonical WNT/β-catenin-signalling. In contrast, IRX5−/− cells displayed activation of Hippo and non-canonical WNT-signalling and generated small tumours with abundant tubulogenesis. Our findings suggest that promotion of IRX3 signalling or inhibition of IRX5 signalling could be a route towards differentiation therapy for Wilms tumour, in which WNT5A is a candidate molecule for enforced tubular maturation.
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38.
  • Jakobsdottir, Johanna, et al. (författare)
  • Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease
  • 2016
  • Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:10
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (similar to 0.5% versus < 0.05% in other European populations). In 433 LOAD cases and 3903 controls from the Icelandic AGES substudy, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI) = 7.5 (3.5-15.9), p = 6.6x10(-9)]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the beta-amyloid cascade.
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39.
  • Jansson, Caroline, et al. (författare)
  • A Swedish study of midwives' and nurses' experiences when women are diagnosed with a missed miscarriage during a routine ultrasound scan
  • 2010
  • Ingår i: Sexual & Reproductive HealthCare. - : Elsevier BV. - 1877-5756 .- 1877-5764. ; 1:2, s. 67-72
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The aim was to describe midwives' and nurses' experiences when women are diagnosed with a missed miscarriage during a routine ultrasound scan in pregnancy weeks 18-20.STUDY DESIGNS: A qualitative content analysis with an inductive approach and 13 semi-structured interviews were used for data collection from these three domains: midwives at an ultrasound department, midwives at a maternity clinic and nurses at a gynecological ward. Content analysis resulted in six codes, four categories and one primary theme.MAIN OUTCOME MEASURES: The four categories identified were: the interviewees' experiences of women's reactions, support from the midwife and nurse, the interviewees' experiences of men's reactions and communication between care providers and women. The main theme focused on the interviewees' noting that women had a premonition that something was wrong with their pregnancy. This could for example have been in the form of minor bleeding or the fact that pregnancy symptoms had receded and there were no movements by the fetus. The midwives carried out a follow-up with assessment.CONCLUSIONS: Women need confirmation of their premonitions of a missed miscarriage so that a diagnosis can be made as early as possible in their pregnancy. Women and their partners who have suffered a missed miscarriage need extended support on an individual basis in addition to follow-up assistance as assessed by the midwives.
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40.
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41.
  • Jansson, Caroline, et al. (författare)
  • Application of “Swanson’s middle range caring theory” in Sweden after miscarriage
  • 2011
  • Ingår i: International Journal of Clinical Medicine. - : Scientific Research Publishing. - 2158-284X .- 2158-2882. ; 2:2, s. 102-109
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of this study was to apply Swanson’s Middle Range Caring Theory to the follow-up visit with a midwife for Swedish women who have suffered early miscarriage or received care for late missed miscarriage in pregnancy week 18 - 20. Methods: Twenty-five tape recorded interviews with women four weeks after their early miscarriages and thirteen tape recorded semi-structured interviews with midwives and nurses who had the experience of caring for women who have been diagnosed with a missed miscarriage during a routine ultrasound scan. The interviews were transcribed verbatim and interpreted deductively from the text using the theory. Results : Each woman described her personal experience of miscarriage in the relative terms of a human experience. The midwives and nurses described their experiences with women who received care for missed miscarriage. The interviews included information about the treatment provided by the caregivers during the period afterward of the diagnosis. The caregiver attitude was formed from Swanson’s caring categories: “Maintaining belief”, “knowing”, “being with”, “doing for”, “enabling”. Conclusions: Swanson’s Middle Range Caring Theory as applied to the caregiver includes being emotionally present, giving support with respect for the woman’s dignity, being competent, meeting each woman’s own individual needs. Given the proper care after a miscarriage every woman has the power within herself to improve their wellbeing.
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42.
  •  
43.
  • Jansson, Caroline, 1963- (författare)
  • Experiences of Miscarriage
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Experiences are unique and both men and women experience grief, anxiety, depressive symptoms after a miscarriage.The overall aim was to describe and measure experiences among women and men after a miscarriage.Study one was a qualitative study with interviews with Swedish midwives' and nurses' experiences of women's reactions after routine ultrasonographic diagnosis of a missed miscarriage.Study two concerned validation of "The revised impact of miscarriage scale" for Swedish conditions and a comparison of Swedish and American women's and men's experiences of miscarriage.Study three was a longitudinal study of Swedish women's and men's emotions.Study four was a longitudinal study, on women's feelings in relation to diagnosis and treatment.Scales about experiences, grief, and depressive symptom were used.The results showed that midwives perceived that the women had had a premonition of symptoms of a missed miscarriage and a follow-up was performed. The degree of consistency showed that the questionnaire can be used in a Swedish setting. The Swedish and American women and men scored similarly in two factors, and the women's experiences were more pronounced than the men's. Grief and depressive symptoms became reduced over time, while experiences persisted. No previous children, miscarriage or infertility treatment prior to miscarriage made the experience worse especially grief reaction. There was no difference between the two diagnosis groups in experiences one week after the miscarriage and their experience improved after four months. Women treated with misoprostol had more depressive symptoms than women treated with misoprostol and subsequent vacuum aspiration.In conclusion, care providers can confirm women's premonition of a missed miscarriage so a diagnosis can be set early in the pregnancy and they can do an individual follow-up. The high consistency between the countries in two factors show that RIMS is reliable for both women and men. Grief and depressive symptoms become reduced, while experiences persist. Previous miscarriage, lack of previous children and an infertility diagnosis can lead to negative feelings as grief. A diagnosis of miscarriage has a limited influence on experiences, and a shorter duration of treatment and treatment with misoprostol and subsequent vacuum aspiration led to a fewer depressive symptom.
  •  
44.
  • Jansson, Caroline, et al. (författare)
  • Retinoic acid promotes differentiation of WiT49- but not of CCG99-11 Wilms tumour cells
  • 2023
  • Ingår i: Cancer Reports. - 2573-8348. ; 6:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Most children with Wilms tumour are successfully treated with multidrug chemotherapy and surgery. These treatments cause severe side effects for the patients, an issue that needs to be addressed by exploring other treatment options with less or no side effects. One option is to complement current therapies with agents that could potentially induce tumour cell differentiation, for example retinoic acid (RA). Aims: To facilitate quick assessment of an agent's effect on Wilms tumour differentiation by a rapid in vitro model system. Methods and Results: Here WiT49 and CCG99-11 Wilms tumour cells were treated with 10 μM RA for 72 h or 9 days. Cultured cells were scraped off from Petri dishes, pelleted and embedded in paraffin in the same way as clinical tumour specimens are preserved. Cell morphology and differentiation were evaluated by analyses of haematoxylin eosin (H&E) and immunohistochemical stainings. Based on H&E, WT1 and CKAE1/3 stainings, RA treatment induced further epithelial differentiation of WiT49 cells, whereas there was no sign of induced maturation in CCG99-11 cells. Ki67 staining showed that RA inhibited cell proliferation in both cell lines. Conclusions: Our study shows that in vitro culturing of WiT49 and CCG99-11 cells, followed by pelleting and paraffin embedding of cell pellets, could aid in a quick evaluation of potential differentiating agents against Wilms tumour. In addition, our results strengthen previous results that retinoic acid could be a potential complement to regular Wilms tumour treatment.
  •  
45.
  •  
46.
  • Jansson, Caroline, et al. (författare)
  • Validation of the Revised Impact of Miscarriage Scale for Swedish conditions and comparison between Swedish and American couples' experiences after miscarriage
  • 2017
  • Ingår i: European journal of contraception & reproductive health care. - : Informa UK Limited. - 1362-5187 .- 1473-0782. ; 22:6, s. 412-417
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: There is a lack of knowledge in women's and men's experience of miscarriage. The Revised Impact of Miscarriage Scale (RIMS) has been used in United States to measure the experiences after miscarriage. The first objective was to test the consistency of RIMS for Swedish conditions. The second purpose of this study was to compare Swedish and American couples' experience of miscarriage by use of the RIMS.METHODS: Forward and back translation was used for translating RIMS into Swedish. This is a hospital-based comparative study including Swedish couples (n = 70) and American couples (n = 70). The couples were matched by the women's age, week of miscarriage and number of children. All participants answered socio-demographic, fertility and depression-scale questions in addition to RIMS.RESULTS: Cronbach's alpha analysis was above 0.650, the mean value was 0.824. There was no significant difference between the Swedish and American participants on the factors 'Isolation/Guilt' and 'Devastating event', but the Swedish women and men scored significantly lower on the factor 'Loss of baby' than the American women and men. The men, Swedish and American combined, scored lower than the women in all factors but the correlation within the couples was similar for both Swedish and American couples.CONCLUSIONS: The high consistency between the countries suggests that the RIMS questionnaire is reliable for both women and men to be used in both countries and two of three factors were similar between the two countries.
  •  
47.
  • Jansson, Desiree S., et al. (författare)
  • Post mortem findings and their relation to AA amyloidosis in free-ranging Herring gulls (Larus argentatus)
  • 2018
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 13:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Since the late 1990s, high mortality and declining populations have been reported among sea birds including Herring gulls ( Larus argentatus) from the Baltic Sea area in Northern Europe. Repeated BoNT type C/D botulism outbreaks have occurred, but it remains unclear whether this is the sole and primary cause of mortality. Thiamine deficiency has also been suggested as a causal or contributing factor. With this study, we aimed to investigate gross and microscopic pathology in Herring gulls from affected breeding sites in Sweden in search of contributing diseases. Herring gulls from Iceland served as controls. Necropsies and histopathology were performed on 75 birds, of which 12 showed signs of disease at the time of necropsy. Parasites of various classes and tissues were commonly observed independent of host age, e.g. oesophageal capillariosis and nematode infection in the proventriculus and gizzard with severe inflammation, air sac larid pentastomes and bursal trematodiasis in pre-fledglings. Gross and microscopic findings are described. Notably, amyloidosis was diagnosed in 93 and 33% of the adult birds from Sweden and Iceland, respectively ( p<0.001), with more pronounced deposits in Swedish birds ( p<0.001). Gastrointestinal deposits were observed in the walls of arteries or arterioles, and occasionally in villi near the mucosal surface. Amyloid was identified within the intestinal lumen in one severely affected gull suggesting the possibility of oral seeding and the existence of a primed state as previously described in some mammals and chickens. This could speculatively explain the high occurrence and previously reported rapid onset of amyloidosis upon inflammation or captivity in Herring gulls. Amyloid-induced malabsorbtion is also a possibility. The Herring gull SAA/AA protein sequence was shown to be highly conserved but differed at the N-terminus from other avian species.
  •  
48.
  •  
49.
  • Jansson, Karin Hassan, 1966-, et al. (författare)
  • Ortsbeskrivningar
  • 2020
  • Ingår i: Fantastiska verb. - Uppsala : Swedish Science Press. - 9789198450934 ; , s. 47-71
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
  •  
50.
  • Jansson, Leif, et al. (författare)
  • Functional stimulation of graft nerves has minor effects on insulin release from transplanted rat pancreatic islets
  • 2013
  • Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 118:4, s. 209-216
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction. Morphological evidence for reinnervation of pancreatic islet grafts is plentiful. However, to what extent intra-graft nerves influence the endocrine functions of the islet transplant is largely unknown. We therefore aimed to directly stimulate nerves leading to islet grafts with electrodes and measure insulin secretion in response to this.Methods. We implanted syngeneic islets under the renal capsule of rats, and examined them 1 or 7-9 months later. In anesthetized rats blood samples were collected from the renal vein and femoral artery, respectively, during electrode stimulation of the nerves leading to the islet grafts. Results. As expected, nerve stimulation decreased renal blood flow. However, serum insulin concentrations in samples derived from the renal vein or femoral artery changed in concert with one another, both during normoglycemia and acute hyperglycemia.Conclusion. Reinnervation which occurs after islet transplantation under the renal capsule has minor effects on graft endocrine function.
  •  
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