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1.
  • Gyllensten, Ulf B., et al. (författare)
  • Next Generation Plasma Proteomics Identifies High-Precision Biomarker Candidates for Ovarian Cancer
  • 2022
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Simple Summary Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. The aim of our study was to broadly measure protein biomarkers to find tests for the early detection of ovarian cancer. We found that combinations of 4-7 protein biomarkers can provide highly accurate detection of early- and late-stage ovarian cancer compared to benign conditions. The performance of the tests was then validated in a second independent cohort. Background: Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. Methods: We employed the Explore PEA technology for high-precision analysis of 1463 plasma proteins and conducted a discovery and replication study using two clinical cohorts of previously untreated patients with benign or malignant ovarian tumours (N = 111 and N = 37). Results: The discovery analysis identified 32 proteins that had significantly higher levels in malignant cases as compared to benign diagnoses, and for 28 of these, the association was replicated in the second cohort. Multivariate modelling identified three highly accurate models based on 4 to 7 proteins each for separating benign tumours from early-stage and/or late-stage ovarian cancers, all with AUCs above 0.96 in the replication cohort. We also developed a model for separating the early-stage from the late-stage achieving an AUC of 0.81 in the replication cohort. These models were based on eleven proteins in total (ALPP, CXCL8, DPY30, IL6, IL12, KRT19, PAEP, TSPAN1, SIGLEC5, VTCN1, and WFDC2), notably without MUCIN-16. The majority of the associated proteins have been connected to ovarian cancer but not identified as potential biomarkers. Conclusions: The results show the ability of using high-precision proteomics for the identification of novel plasma protein biomarker candidates for the early detection of ovarian cancer.
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3.
  • Andernord, D., et al. (författare)
  • Contact allergy to haptens in the Swedish baseline series: Results from the Swedish Patch Test Register (2010 to 2017)
  • 2022
  • Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 86:3, s. 175-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Allergic contact dermatitis has considerable public health impact and causative haptens vary over time. Objectives To report the prevalence of contact allergy to allergens in the Swedish baseline series 2010 to 2017, as registered in the Swedish Patch Test Register. Methods Results and demographic information for patients tested with the Swedish baseline series in 2010 to 2017 were analysed. Results Data for 21 663 individuals (females 69%) were included. Females had significantly more positive patch tests (54% vs 40%). The reaction prevalence rates were highest for nickel sulfate (20.7%), fragrance mix I (7.1%), Myroxylon pereirae (6.9%), potassium dichromate (6.9%), cobalt chloride (6.8%), methylchloroisothiazolinone/methylisothiazolinone (MCI/MI; 6.4%), MI (3.7%), colophonium (3.5%), fragrance mix II (3.2%), and formaldehyde (3.2%). Myroxylon pereirae reaction prevalence increased from 5% in 2010 to 9% in 2017 and that for methyldibromo glutaronitrile from 3.1% to 4.6%. MCI/MI and MI reactions decreased in prevalence after 2014. Nickel reaction prevalence decreased among females aged 10 to 19 years. Conclusions Nickel remains the most common sensitizing agent, with reaction prevalence decreasing among females younger than 20 years. The changes in MCI/MI and MI reaction prevalence mirrored those in Europe. The register can reveal changes in contact allergy prevalence over time among patients patch tested in Sweden.
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  • Ansari, Daniel, et al. (författare)
  • Surveillance after surgery for pancreatic cancer : a global scoping review of guidelines and a nordic survey of contemporary practice
  • 2024
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708.
  • Forskningsöversikt (refereegranskat)abstract
    • Objectives: Most patients with pancreatic cancer who have undergone surgical resection eventually develop disease recurrence. ‍This study aimed to investigate whether there is evidence to support routine surveillance after pancreatic cancer surgery, with a secondary aim of analyzing the implementation of surveillance strategies in the Nordic countries.Materials and Methods: A scoping review was conducted to identify clinical practice guidelines globally and research studies relating to surveillance after pancreatic cancer resection. This was followed by a survey among 20 pancreatic units from four Nordic countries to assess their current practice of follow-up for operated patients.Results: Altogether 16 clinical practice guidelines and 17 research studies were included. The guidelines provided inconsistent recommendations regarding postoperative surveillance of pancreatic cancer. The clinical research data were mainly based on retrospective cohort studies with low level of evidence and lead-time bias was not addressed. Active surveillance was recommended in Sweden and Denmark, but not in Norway beyond the post-operative/adjuvant period. Finland had no national recommendations for surveillance. The Nordic survey revealed a wide variation in reported practice among the different units. About 75% (15 of 20 units) performed routine postoperative surveillance. Routine CA 19-9 testing was used by 80% and routine CT by 67% as part of surveillance. About 73% of centers continued follow-up until 5 years postoperatively.Conclusion: Evidence for routine long-term (i.e. 5 years) surveillance after pancreatic cancer surgery remains limited. Most pancreatic units in the Nordic countries conduct regular follow-up, but protocols vary.
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6.
  • Backman, Max, et al. (författare)
  • Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer
  • 2021
  • Ingår i: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 255:3, s. 243-256
  • Tidskriftsartikel (refereegranskat)abstract
    • Immune cells of the tumor microenvironment are central but erratic targets for immunotherapy. The aim of this study was to characterize novel patterns of immune cell infiltration in non-small cell lung cancer (NSCLC) in relation to its molecular and clinicopathologic characteristics. Lymphocytes (CD3+, CD4+, CD8+, CD20+, FOXP3+, CD45RO+), macrophages (CD163+), plasma cells (CD138+), NK cells (NKp46+), PD1+, and PD-L1+ were annotated on a tissue microarray including 357 NSCLC cases. Somatic mutations were analyzed by targeted sequencing for 82 genes and a tumor mutational load score was estimated. Transcriptomic immune patterns were established in 197 patients based on RNA sequencing data. The immune cell infiltration was variable and showed only poor association with specific mutations. The previously defined immune phenotypic patterns, desert, inflamed, and immune excluded, comprised 30, 13, and 57% of cases, respectively. Notably, mRNA immune activation and high estimated tumor mutational load were unique only for the inflamed pattern. However, in the unsupervised cluster analysis, including all immune cell markers, these conceptual patterns were only weakly reproduced. Instead, four immune classes were identified: (1) high immune cell infiltration, (2) high immune cell infiltration with abundance of CD20+ B cells, (3) low immune cell infiltration, and (4) a phenotype with an imprint of plasma cells and NK cells. This latter class was linked to better survival despite exhibiting low expression of immune response-related genes (e.g. CXCL9, GZMB, INFG, CTLA4). This compartment-specific immune cell analysis in the context of the molecular and clinical background of NSCLC reveals two previously unrecognized immune classes. A refined immune classification, including traits of the humoral and innate immune response, is important to define the immunogenic potency of NSCLC in the era of immunotherapy. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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  • Backman, Max, 1987-, et al. (författare)
  • Spatial immunophenotyping of the tumor microenvironment in non-small cell lung cancer
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Immune cells in the tumor microenvironment are associated with prognosis and response to therapy. We aimed to comprehensively characterize the spatial immune phenotypes in the mutational and clinicopathological background of non-small cell lung cancer (NSCLC).Methods: We established a multiplexed fluorescence multispectral imaging pipeline to spatially quantify 13 immune cell subsets in 359 NSCLC cases: CD4 effector cells (CD4 Eff), CD4 regulatory cells (CD4 Treg), CD8 effector cells (CD8 Eff), CD8 regulatory cells (CD8 Treg), B-cells, NK-cells, NKT-cells, M1 macrophages (M1), CD163+ myeloid cells (CD163), M2 macrophages (M2), immature dendritic cells (iDCs), mature dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs).  Results: CD4 Eff cells, CD8 Eff cells, and M1 macrophages were the most abundant immune cells invading the tumor cell compartment and indicated a patient group with a favorable prognosis in the cluster analysis. Likewise, single densities of lymphocytic subsets (CD4 Eff, CD4 Treg, CD8 Treg, and B-cells), as well as pDCs, were independently associated with longer survival. However, when these immune cells were located close to CD8 Treg cells, the favorable impact was attenuated. In the multivariate Cox regression model including cell densities and distances, the densities of M1 and CD163 cells and distances between cells (CD8 Treg–B-cells, CD8 Eff–cancer cells, and B-cells–CD4 Treg) demonstrated positive prognostic impact, while short M2–M1 distances were prognostically unfavorable.Conclusion: We present a unique spatial profile of the in situ immune cell landscape in NSCLC as a publicly available data set. Cell densities and cell distances contribute independently to prognostic information on clinical outcomes, suggesting that spatial information is also crucial for diagnostic use.
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  • Backman, Max, 1987-, et al. (författare)
  • Spatial immunophenotyping of the tumour microenvironment in non-small cell lung cancer
  • 2023
  • Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 185, s. 40-52
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Immune cells in the tumour microenvironment are associated with prognosis and response to therapy. We aimed to comprehensively characterise the spatial im-mune phenotypes in the mutational and clinicopathological background of non-small cell lung cancer (NSCLC).Methods: We established a multiplexed fluorescence imaging pipeline to spatially quantify 13 immune cell subsets in 359 NSCLC cases: CD4 effector cells (CD4-Eff), CD4 regulatory cells (CD4-Treg), CD8 effector cells (CD8-Eff), CD8 regulatory cells (CD8-Treg), B-cells, natural killer cells, natural killer T-cells, M1 macrophages (M1), CD163 thorn myeloid cells (CD163), M2 macrophages (M2), immature dendritic cells (iDCs), mature dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs).Results: CD4-Eff cells, CD8-Eff cells and M1 macrophages were the most abundant immune cells invading the tumour cell compartment and indicated a patient group with a favourable prognosis in the cluster analysis. Likewise, single densities of lymphocytic subsets (CD4-Eff, CD4-Treg, CD8-Treg, B-cells and pDCs) were independently associated with longer survival. However, when these immune cells were located close to CD8-Treg cells, the favourable impact was attenuated. In the multivariable Cox regression model, including cell densities and distances, the densities of M1 and CD163 cells and distances between cells (CD8-Treg-B-cells, CD8-Eff-cancer cells and B-cells-CD4-Treg) demonstrated positive prognostic impact, whereas short M2-M1 distances were prognostically unfavourable.Conclusion: We present a unique spatial profile of the in situ immune cell landscape in NSCLC as a publicly available data set. Cell densities and cell distances contribute independently to prognostic information on clinical outcomes, suggesting that spatial information is crucial for diagnostic use.
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  • Björkman, Kristoffer, et al. (författare)
  • Phenotypic spectrum and clinical course of single large-scale mitochondrial DNA deletion disease in the paediatric population: a multicentre study.
  • 2021
  • Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 60:1, s. 65-73
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Large-scale mitochondrial DNA deletions (LMD) are a common genetic cause of mitochondrial disease and give rise to a wide range of clinical features. Lack of longitudinal data means the natural history remains unclear. This study was undertaken to describe the clinical spectrum in a large cohort of patients with paediatric disease onset. Methods A retrospective multicentre study was performed in patients with clinical onset <16 years of age, diagnosed and followed in seven European mitochondrial disease centres. Results A total of 80 patients were included. The average age at disease onset and at last examination was 10 and 31 years, respectively. The median time from disease onset to death was 11.5 years. Pearson syndrome was present in 21%, Kearns-Sayre syndrome spectrum disorder in 50% and progressive external ophthalmoplegia in 29% of patients. Haematological abnormalities were the hallmark of the disease in preschool children, while the most common presentations in older patients were ptosis and external ophthalmoplegia. Skeletal muscle involvement was found in 65% and exercise intolerance in 25% of the patients. Central nervous system involvement was frequent, with variable presence of ataxia (40%), cognitive involvement (36%) and stroke-like episodes (9%). Other common features were pigmentary retinopathy (46%), short stature (42%), hearing impairment (39%), cardiac disease (39%), diabetes mellitus (25%) and renal disease (19%). Conclusion Our study provides new insights into the phenotypic spectrum of childhood-onset, LMD-associated syndromes. We found a wider spectrum of more prevalent multisystem involvement compared with previous studies, most likely related to a longer time of follow-up.
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  • Burström, Bo, et al. (författare)
  • Healthcare utilisation and measles, mumps and rubella vaccination rates among children with an extended postnatal home visiting programme in a disadvantaged area in Stockholm, Sweden - A 3‐year follow‐up
  • 2020
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 109:9, s. 1847-1853
  • Tidskriftsartikel (refereegranskat)abstract
    • AimTo follow up healthcare utilisation and measles, mumps and rubella (MMR) vaccination rates among children 0-36 months, receiving an extended postnatal home visiting programme in a disadvantaged area with poorer child health, and in control groups, in Stockholm, Sweden.MethodsWe analysed electronic child health records regarding outpatient visits, inpatient episodes and MMR vaccination for children 0-36 months receiving the home visiting programme (Intervention Group) and in control groups (Control Group and Rinkeby Comparison Group).ResultsChildren in the Intervention Group had significantly higher MMR vaccination rate than children in the Rinkeby Comparison Group. Healthcare utilisation was similar in the Intervention Group and the control groups. In stratified analyses by number of home visits received, children receiving the recommended six home visits had significantly fewer inpatient episodes and somewhat fewer emergency visits than those receiving fewer home visits.ConclusionThe extended home visiting programme had a positive impact on the MMR vaccination rate. Children receiving the recommended six home visits had lower use of inpatient care. In addition to being positively perceived by parents in an area with greater healthcare needs, the programme may have a positive impact on their children's healthcare utilisation.
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12.
  • Christel, Borg, et al. (författare)
  • Problem-based learning with digitals tools in the nursing programme during the Covid-19 pandemic
  • 2022
  • Ingår i: Högre Utbildning. - : Cappelen Damm Akademisk. - 2000-7558. ; 12:2, s. 117-122
  • Tidskriftsartikel (refereegranskat)abstract
    • During the spring 2019, the prerequisites for conducting education were changed due to the pandemic. For higher education in Sweden almost all education switches on to digital education. Nursing education has focus on both theoretical and practical courses, which is a challenge for digital or distance education. Furthermore, the nursing programme at the studied university used problem-based learning (PBL), with base-groups at campus. Instead of physical meetings at campus, the base-groups took part with digital tools. The impact of base-groupsmeeting with digital tools are important to reflect on, especially since the education and learning of future probably will be more hybrid. © 2022 Christel Borg, Johanna Tell, Terese Lindberg, Lina Nilsson, Anki Olsson, Malin Forsbrand & Lisa Skär.
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13.
  • Dolinska, Monika, et al. (författare)
  • Characterization of Bone Marrow Niche in Chronic Myeloid Leukemia Patients Identifies CXCL14 as a New Therapeutic Option
  • 2023
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 142:1, s. 73-89
  • Tidskriftsartikel (refereegranskat)abstract
    • Although tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be because of bone marrow (BM) niche protection; however, little is known about the underlying mechanisms. Herein, we molecularly and functionally characterize BM niches in patients with CML at diagnosis and reveal the altered niche composition and function in these patients. Long-term culture initiating cell assay showed that the mesenchymal stem cells from patients with CML displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in the BM cellular niches of patients with CML. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in patient-derived xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs.
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14.
  • Dolinska, Monika, et al. (författare)
  • Characterization of the bone marrow niche in patients with chronic myeloid leukemia identifies CXCL14 as a new therapeutic option
  • 2023
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 142:1, s. 73-89
  • Tidskriftsartikel (refereegranskat)abstract
    • Although tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be because of bone marrow (BM) niche protection; however, little is known about the underlying mechanisms. Herein, we molecularly and functionally characterize BM niches in patients with CML at diagnosis and reveal the altered niche composition and function in these patients. Long -term culture initiating cell assay showed that the mesenchymal stem cells from patients with CML displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in the BM cellular niches of patients with CML. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in patient-derived xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs.
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  • Engert, Andreas, et al. (författare)
  • The European Hematology Association Roadmap for European Hematology Research : a consensus document
  • 2016
  • Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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  • Fischl, Caroline, 1974-, et al. (författare)
  • Kontinuitet i uppgifter inom år 3 arbetsterapeutprogrammet
  • 2015
  • Ingår i: Universitetspedagogiska konferensen 2015. - Umeå : Universitetspedagogik och lärandestöd (UPL), Umeå universitet. ; , s. 66-66
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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  • Fischl, Caroline, et al. (författare)
  • Kontinuitet i uppgifter inom år 3 arbetsterapeutprogrammet
  • 2015
  • Ingår i: Universitetspedagogiska konferensen 2015. ; , s. 66-66
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Syftet med vår poster är att illustrera kontinuitet i examinationsuppgifterna och progression i lärandet under kurserna i år 3 arbetsterapeutprogrammet.Under höstterminen 2014 till och med vårterminen 2015 genomfördes för första gången kurser i det tredje och sista året inom det reviderade arbetsterapeutprogrammet. Dessa kurser handlar om praktiska tillämpningar av kunskaper om projektledning och förändringsarbete, vetenskaplig metod samt arbetsterapeutiska teorier och modeller inom traditionella och nya arenor. Studenterna förväntas utveckla ett reflekterande förhållningssätt och arbetsterapeutisk professionalitet i samverkan med andra samt beredskap att uppfylla olika roller i arbetslivet.Kontinuitet uppnås när studenten under den första kursen skriver en plan för examensarbete (kurs 2) och/eller förändringsarbete (kurs 4). Studenten kan också välja att skriva en plan för verksamhetsutveckling (kurs 3) och implementera planen i den sista kursen. Under examensarbete får studenten välja kvantitativ eller kvalitativ metod, eller litteraturstudie efter intresseområde och koppla arbetet mot innovationskursen. Att kunna arbeta vidare med en idé genom uppgifterna i olika kurser kan göra studenten mer engagerad i sitt lärande. Studenten genomgår också en process genom att utveckla och testa idéer under ett antal iterationer.Progression i lärandet sker även vid upprepning av pedagogiska metoder. Till exempel, har lärandekontraktet under verksamhetsförlagd utbildning (kurs 3) fokus på identifiering och formulering av lärandemål, medan under innovationskursen (kurs 4) har uppgiften fokus på identifiering av handlingar och stöd som behövs för att uppnå lärandemålen.
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18.
  • Goldmann, Torsten, et al. (författare)
  • PD-L1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung
  • 2021
  • Ingår i: Cancer Immunology and Immunotherapy. - : Springer Nature. - 0340-7004 .- 1432-0851. ; 70:9, s. 2577-2587
  • Tidskriftsartikel (refereegranskat)abstract
    • Gene amplification is considered to be one responsible cause for upregulation of Programmed Death Ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC) and to represent a specific molecular subgroup possibly associated with immunotherapy response. Our aim was to analyze the frequency of PD-L1 amplification, its relation to PD-L1 mRNA and protein expression, and to characterize the immune microenvironment of amplified cases. The study was based on two independent NSCLC cohorts, including 354 and 349 cases, respectively. Tissue microarrays were used to evaluate PD-L1 amplification by FISH and PD-L1 protein by immunohistochemistry. Immune infiltrates were characterized immunohistochemically by a panel of immune markers (CD3, CD4, CD8, PD-1, Foxp3, CD20, CD138, CD168, CD45RO, NKp46). Mutational status was determined by targeted sequencing. RNAseq data was available for 197 patients. PD-L1 amplification was detected in 4.5% of all evaluable cases. PD-L1 amplification correlated only weakly with mRNA and protein expression. About 37% of amplified cases were negative for PD-L1 protein. PD-L1 amplification did not show any association with the mutational status. In squamous cell cancer, PD-L1 amplified cases were enriched among patients with high tumoral immune cell infiltration and showed gene expression profiles related to immune exhaustion. In conclusion, PD-L1 amplification correlates with PD-L1 expression in squamous cell cancer and was associated with an immune cell rich tumor phenotype. The correlative findings help to understand the role of PD-L1 amplification as an important immune escape mechanism in NSCLC and suggest the need to further evaluate PD-L1 amplification as predictive biomarker for checkpoint inhibitor therapy.
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21.
  • Gustafsson, Johanna T, et al. (författare)
  • Excess atherosclerosis in systemic lupus erythematosus A matter of renal involvement : Case control study of 281 SLE patients and 281 individually matched population controls
  • 2017
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Systemic lupus erythematosus (SLE), is a heterogeneous disease which predominantly affects young females (90%). SLE is associated with a shorter life expectancy than in the general population. Standardized mortality ratios (SMR) of 2.4 have been reported, which is comparable to diabetes. In modern societies cardiovascular disease (CVD) is the major cause of premature mortality. Accelerated atherosclerosis is generally assumed to be the underlying cause for SLE related CVD. However, previous studies diverge regarding whether atherosclerosis is more common in SLE than in controls. With this in mind and based on own clinical experience we hypothesized that accelerated atherosclerosis is not a general feature of SLE, but prevails in SLE subgroups.METHODS: 281 SLE patients and 281 individually age and sex matched population controls, were investigated clinically. Fasting blood samples and risk factor data were collected. All participants were subject to B-mode ultrasonography of the carotid arteries. Carotid plaque occurrence and mean intima media thickness (mIMT) were recorded. Two SLE subgroups previously described to be at high CVD risk; 1) patients with nephritis and 2) patients with anti-phospholipid antibodies (aPL), and one subgroup reported to be at comparatively lower CVD risk; patients positive for Sjögren´s syndrome antigens A/B (SSA/SSB) antibodies were analyzed separately in comparison with their respective matched controls.RESULTS: Median age was 49 (IQR 36-59) years, 93% were females. Manifest CVD; ischemic heart, cerebro- and peripheral vascular disease, prevailed in patients (12% vs. 1%, p<0.0001). Overall plaque prevalence did not differ (20% vs. 16%), but patients had slightly higher mIMT than controls (0.56 vs. 0.53 mm, p<0.0033). After age adjustment plaques, but not mIMT, remained associated with previous CVD events. Therefore we focused further analyses on plaques, a more robust measure of atherosclerosis. Patients with nephritis (40%), but neither aPL (25%) nor SSA/SSB (40%) positive patients, had more plaques than their respective controls (23% vs. 11%, p = 0.008). Notably, patients with nephritis were younger than other SLE patients (45 vs.49 years, p = 0.02). To overcome the confounding effect of age we performed an age-matched nested case-control analysis, which demonstrated that patients with nephritis had twice as often plaques (23%) as both non-nephritis patients (11%, p = 0.038) and controls (12%, p = 0.035).CONCLUSIONS: In SLE excess carotid plaques are essentially confined to the SLE subgroup with nephritis. This subgroup had plaques twice as often as age-matched non-nephritis SLE patients and population controls. Non-nephritis SLE patients, including the aPL positive subgroup, which has a high CVD risk, had similar prevalence of plaques as controls. To prevent later CVD events, this novel observation calls for risk factor screening and initiation of anti-atherosclerotic treatment selectively in SLE nephritis patients. Preferably at nephritis onset, which is often at a young age. In a general perspective this study demonstrates the importance to perform careful clinical subgroup analyses when investigating heterogeneous, hitherto not clearly defined, conditions like SLE.
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22.
  • Habibipour, Abdolrasoul, 1979-, et al. (författare)
  • Rural Living Lab: What is that and how is it shaped?
  • 2021
  • Ingår i: Proceedings of the Digital Living Lab Days Conference 2021. - : European Network of Living Labs (ENoLL). ; , s. 127-141
  • Konferensbidrag (refereegranskat)abstract
    • Digital transformation (DT) has received increasing attention in recent years. Despite this, most of the current studies focus on digital transformation in more advanced societies, particularly urban areas, and the concept has not been investigated enough within rural contexts. This study aims at exploring how a rural living lab (Rural LL) is shaped and how this approach can be designed to support digital transformation processes in rural context. In so doing, following a design science research methodology (DSRM), we have designed an artefact (i.e., Rural LL framework) which is an “instantiation” that supports user centric digitalization of rural areas. The designed framework is developed based on the key components of “traditional” and “urban” living labs, as well as empirical data which was collected within the context of the DigiBy project. The main constructs (key components) of this framework are: 1) rural context, 2) digitalization, 3) governance, control, and business mode, and 4) quintuple helix actors. We also offer an empirically derived definition of the rural living lab concept, followed by avenues for future research.
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23.
  • Habibipour, Abdolrasoul, 1979-, et al. (författare)
  • Rural Living Labs: Inclusive Digital Transformation in the Countryside
  • 2021
  • Ingår i: Technology Innovation Management Review. - Ottawa : Talent First Network. - 1927-0321. ; 11:9/10, s. 59-72
  • Tidskriftsartikel (refereegranskat)abstract
    • Digital transformation (DT) has received increasing attention in recent years. Up until now, most of the current studies focus on digital transformation in advanced and dense societies, especially urban areas and technologies. Hence, the phenomenon of DT is under-researched in the context of rural and sparsely populated contexts. This study aims at exploring how a rural living lab (RLL) can be shaped and how this approach can be designed to support digital transformation processes in rural contexts. In so doing, following a design science research methodology (DSRM) approach, we have made an artefact (that is, RLL framework) that is an “instantiation” that supports user centric digitalization of rural areas. The designed framework is developed based on the key components of “traditional” and “urban” living labs, as well as empirical data which was collected within the context of the DigiBy project. The DigiBy project aims at conducting DT pilots in rural areas to elevate peoples’ understanding of digitalization and the application of digitalization opportunities for service development in rural areas in the north of Sweden. As a result of these studies, five key components that guide the design of digital transformation pilots in rural areas emerged, namely: 1) rural context, 2) digitalization, 3) governance, control, and business mode, 4) methods facilitating DT processes, and 5) quintuple helix actors. We also offer an empirically derived definition of the rural living lab concept, followed by avenues for future research.
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24.
  • Habibipour, Abdolrasoul, 1979-, et al. (författare)
  • Theorizing Living Lab research: The way forward
  • 2023
  • Ingår i: Proceedings of the XXXIV ISPIM Innovation Conference. - 9789526506937
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Living Labs have become a popular approach to facilitate multi-stakeholder engagement in open innovation processes in real-life settings. Despite their extensive application across various research fields, there is still a lack of theoretical understanding in this area. This study aims to take the first step towards developing a theory for Living Labs. In doing so, we will review the current state of the art of Living Lab theories as well as identify areas where further theoretical support is required. To achieve this, grounded theory will be used as the overarching approach to rigorously review literature. The outcome of this research will be a taxonomy of Living Lab theories, classified according to the emerged themes from grounded theory analysis. Additionally, the study will identify areas where Living Lab research needs to be theorized to support both researchers and practitioners in this area.
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25.
  • Hagvall, Lina, 1978, et al. (författare)
  • Contact allergy to citral and its constituents geranial and neral, coupled with reactions to the prehapten and prohapten geraniol
  • 2020
  • Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 82:1, s. 31-38
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Citral is commonly used as a fragrance and flavor material and consists of the aldehydes geranial and neral. Citral is included in fragrance mix (FM) II. Geranial and neral have also been identified in autoxidation of geraniol, a fragrance compound present in FM I. Objectives To study contact allergy to citral, geranial, and neral, and concomitant reactivity to oxidized geraniol and fragrance markers of the baseline series. Methods A total of 1476 dermatitis patients with suspected allergic contact dermatitis were patch tested using geranial, neral, and citral, all 3.5% petrolatum (pet.) as well as geraniol 6.0% and oxidized geraniol 11% pet. in addition to the Swedish baseline series. Results Frequencies of positive reactions to citral, geranial, and neral were 2.9%, 3.4% and 1.9%, respectively. Together, citral and geranial gave 4.2% positive patch test reactions in consecutive dermatitis patients. In patients with positive reactions to citral or its components, 25% to 34% reacted to FM II and 61% reacted to oxidized geraniol. Conclusions Patch testing with citral, its components, or oxidized geraniol detects contact allergic reactions not detected using the baseline series. Patch testing with pure geraniol was shown to be of little value. Geranial and neral, although closely chemically related, are concluded to be separate haptens.
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26.
  • Hagvall, Lina, 1978, et al. (författare)
  • Contact allergy to oxidized geraniol among Swedish dermatitis patients-A multicentre study by the Swedish Contact Dermatitis Research Group
  • 2018
  • Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 79:4, s. 232-238
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Geraniol is a widely used fragrance terpene, and is included in fragrance mix I. Geraniol is prone to autoxidation, forming the skin sensitizers geranial, neral, and geraniol-7-hydroperoxide. Oxidized geraniol has previously been patch tested in 1 clinic, giving 1% to 4.6% positive reactions in consecutive patients when tested at 2% to 11%. Aim: To compare test reactions to pure and oxidized geraniol, to compare 2 different test concentrations of oxidized geraniol and to investigate the pattern of concomitant reactions to fragrance markers of the baseline series in a multicentre setting. Methods: One thousand four hundred and seventy-six consecutive patients referred for patch testing were patch tested with geraniol 6% pet. and oxidized geraniol 6% and 11% pet. Results: Pure geraniol 6% pet., oxidized geraniol 6% pet. and oxidized geraniol 11% pet. gave 1%, 3% and 8% positive patch test reactions and 0.7%, 3% and 5% doubtful reactions, respectively. Approximately 50% of the patients with doubtful reactions to oxidized geraniol 6% pet. had positive reactions to oxidized geraniol 11% pet. Conclusions: Oxidized geraniol 11% pet. provides better detection than oxidized geraniol 6% pet. As most patients reacted only to oxidized geraniol, it is important to explore further whether oxidized geraniol should be included in a baseline patch test series.
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27.
  • Hallikas, Outi K, et al. (författare)
  • Identification of Antibodies against HAI-1 and Integrin {alpha}6{beta}4 as
  • 2006
  • Ingår i: Journal of Histochemistry and Cytochemistry. - 0022-1554 .- 1551-5044. ; 54:7, s. 754-752
  • Tidskriftsartikel (refereegranskat)abstract
    • Syncytiotrophoblast and invasive extravillous trophoblast arise from a common stem cell, namely villous cytotrophoblast, but have very different characteristics. The study of the differentiation process relies on the availability of suitable markers for these different cell types of developing placenta. In this work, we have produced monoclonal antibodies that are specific to human villous cytotrophoblast. Monoclonal antibody (MAb) MG2 was specific to villous cytotrophoblast across gestation,                     and recognizes hepatocyte growth factor activator inhibitor type 1. MAb MD10 stained villous cytotrophoblast across gestation and also some endothelial cells, particularly in the second or third trimester. MAb MD10 recognizes human integrin α6β4. As a test for specificity, the novel MAbs were also used for staining of frozen tissue from human colon carcinoma. The results show that the two antibodies can be used as tools to study human villous cytotrophoblasts and also human tumors. The MG2 antibody seems most specific and promising for the study of various aspects of human villous cytotrophoblast.                 
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28.
  • Hovold, Gisela, et al. (författare)
  • BPI-ANCA is expressed in the airways of cystic fibrosis patients and correlates to platelet numbers and Pseudomonas aeruginosa colonization
  • 2020
  • Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111. ; 170
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Autoantibodies to bactericidal/permeability-increasing protein (BPI), BPI-ANCA, are often present in serum of patients with cystic fibrosis (CF), and correlate to airway colonization with Pseudomonas aeruginosa. The aim of the study was to investigate if BPI-ANCA IgA is also present in the airways of CF patients, and if its presence correlates with neutrophil counts, platelets, and P. aeruginosa DNA in sputum. Methods: BPI-ANCA IgA was quantified in serum and sputum samples from adult CF patients (n = 45) by ELISA. Sputum neutrophil counts, platelets, and platelet-neutrophil complexes were assessed by flow cytometry, and P. aeruginosa DNA was analysed with RT-PCR. Results: Serum BPI-ANCA IgA was present in 44% of the study participants, and this group also had significantly enhanced BPI-ANCA levels in sputum compared to serum negative patients. Sputum levels of BPI-ANCA IgA correlated with P. aeruginosa DNA (r = 0.63, p = 0.0003) and platelet counts in sputum (r = 0.60, p = 0.0002). Conclusions: BPI-ANCA is expressed in the airways of CF patients and correlates with P. aeruginosa load and platelet counts, suggesting a link to airway inflammation and mucosal immunity.
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29.
  • Isaksson, Marléne, et al. (författare)
  • Patch Testing with Formaldehyde 2.0% in Parallel with 1.0% by the Swedish Contact Dermatitis Research Group
  • 2014
  • Ingår i: Acta Dermato-Venereologica. - : Taylor & Francis. - 0001-5555 .- 1651-2057. ; 94:4, s. 408-410
  • Tidskriftsartikel (refereegranskat)abstract
    • In a multicentre study consecutively patch-tested dermatitis patients were tested simultaneously with 1.0% and 2.0% (w/v) formaldehyde in aqua applied with a micro-pipette (15 mu l) to the filter paper disc in Finn Chambers (0.30 mg/cm(2) and 0.60 mg/cm(2), respectively). A total of 2,122 dermatitis patients were patch-tested. In all, 77 (3.6%) patients reacted positively to formaldehyde; 37 reacted only to 2.0%, 35 reacted to both concentrations and 5 patients reacted only to 1.0%. Significantly more patients were thus diagnosed with contact allergy to formaldehyde with 2.0% compared to 1.0% (p<0.001) without causing more irritant reactions. The detected number of isolated allergic reactions to the 2 formaldehyde-releasers in the Swedish baseline series and not to formaldehyde itself raises the question whether quaternium-15 1.0% and diazolidinyl urea 2.0% should be present in the Swedish baseline series.
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30.
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31.
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32.
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33.
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34.
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35.
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36.
  • Karlsson, Johanna, et al. (författare)
  • Effects of replacing wheat starch with glycerol on methane emissions, milk production, and feed efficiency in dairy cows fed grass silage-based diets
  • 2019
  • Ingår i: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302 .- 1525-3198. ; 102, s. 7927-7935
  • Tidskriftsartikel (refereegranskat)abstract
    • To lower the effect of climate change from cattle production, we should aim at decreasing their enteric methane emissions per kilogram of milk or meat. Glycerol may be absorbed through the rumen epithelium and would consequently be less available to microbes in the rumen. Glycerol could thus supply dairy cows with energy for milk production without contributing much to methane production. This study evaluated the effect of replacing wheat starch with glycerol on milk production, feed intake, and methane emissions. Twenty-two Swedish Red cows in mid lactation were used in a switch-back, change-over experiment with 3 periods of 21 d. The 2 dietary treatments consisted of a total mixed ration based on (g/kg of dry matter) grass silage (605), rapeseed meal (120), and barley (70) and either wheat starch or refined glycerol (200) fed ad libitum. The glycerol diet resulted in higher dry matter intake (21.6 vs. 20.1 kg/d) and methane emissions (482 vs. 423 g/d) compared with the diet containing wheat starch, whereas no difference was found in energy-corrected milk yield (28.4 vs. 29.7 kg/d). These results indicate that when glycerol is mixed with the feed, it is available to rumen microbes to a larger extent than initially assumed. Compared with wheat starch, adding refined glycerol (200 g/kg of dry matter) to the feed of dairy cows does not seem to have the potential to decrease enteric methane emissions.
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37.
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38.
  • Karlsson, Johanna, et al. (författare)
  • Ensilageintag och mjölkproduktion med lite kraftfoder i tidig laktation
  • 2017
  • Ingår i: Report from the Department of Crop Production Ecology (VPE). - 1653-5375. ; , s. 71-74
  • Konferensbidrag (refereegranskat)abstract
    • Efterfrågan på livsmedel förväntas öka globalt och idag utfodras mjölkkor med stora mängder produkter som lika gärna kunde ha konsumerats direkt av människor. Detta försök undersökte produktionseffekter när kor i tidig laktation fick en liten giva av kraftfoder baserat på fodermedel som inte kan nyttjas som humanföda. Tjugofyra mjölkkor ingick i försöket där hälften av korna erbjöds en liten kraftfodergiva (max 4–5 kg/dag) och den andra hälften en stor kraftfodergiva (max 14–15 kg/dag). De fick dessutom fri tillgång till vallensilage. Det var ingen skillnad i mjölkavkastning, mjölksammansättning eller totalt foderintag mellan grupperna, men nettoproduktionen av livsmedel samt mjölkintäkt minus foderkostnad var större med en låg andel kraftfoder i foderstaten.
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39.
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40.
  • Karlsson, Johanna, et al. (författare)
  • Feed intake, milk yield and metabolic status of early-lactation Swedish Holstein and Swedish Red dairy cows of different parities fed grass silage and two levels of byproduct-based concentrate
  • 2020
  • Ingår i: Livestock Science. - : Elsevier BV. - 1871-1413 .- 1878-0490. ; 242
  • Tidskriftsartikel (refereegranskat)abstract
    • Dairy cows can produce highly nutritive food products (milk, meat etc.) from fibrous feed e.g. grass and different byproducts from the food and fuel industry, that cannot be consumed directly by humans. However, as there are limited amounts of byproducts available, decreasing the amount of byproduct-based concentrate in the diet could be a strategy for improving sustainability within dairy production if high milk production should be maintained. In this study, 26 multiparous (n = 14) and primiparous (n = 12) dairy cows of the breeds Swedish Red (n = 14) and Swedish Holstein (n = 12) were followed between lactation weeks 1 and 6. They were fed either a low-concentrate (n = 13; LC) or high-concentrate (n = 13; HC) byproduct-based (sugar beet pulp, rapeseed meal, distiller's grain, wheat bran) ration, in combination with highly digestible grass-clover silage ad libitum. To achieve similar concentrate intake per kg body weight in primiparous and multiparous cows, multiparous cows were offered 5 kg concentrate on the LC diet and 15 kg concentrate on the HC diet, while primiparous cows were offered 4 kg concentrate on the LC diet and 14 kg concentrate on the HC diet as target concentrate rations. We found no overall differences in dry matter intake, energy-corrected milk yield, energy balance, blood plasma metabolites, blood hormones or milk fatty acids between cows on the LC and HC diets. However, HC cows had a higher yield of ECM in lactation week 6 and gained body weight compared with LC cows. As expected, multiparous cows had higher dry matter intake and energy-corrected milk yield, but we found no difference in energy balance between parities. However, multiparous cows lost more body condition and had higher blood plasma concentrations of non-esterified fatty acids, indicating that they used more body tissue to support milk production. In conclusion, both multiparous and primiparous Swedish Red and Swedish Holstein dairy cows seem able to adapt to low-concentrate diets in early lactation when the diets are based on byproducts and grass-clover silage, providing the potential to increase sustainability in dairy production.
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41.
  • Karlsson, Johanna, et al. (författare)
  • Replacing cereals and soybean meal with sugar beet pulp and rapeseed meal or distiller´s grain in grass silage diets to dairy cows
  • 2016
  • Ingår i: Rapport / Sveriges lantbruksuniversitet, Institutionen för husdjurens utfodring och vård. - 0347-9838. ; , s. 82-86
  • Konferensbidrag (refereegranskat)abstract
    • Introduction Large volumes of human-edible products as cereal grains and soya beans are fed to dairy cows in intensive production systems (Eisler et al., 2014). Given the predicted increase in demand for livestock products and competition of land for food and feed, human inedible feeds are becoming increasingly important. Ruminants have a unique ability to produce high quality food, as milk and meat, from fibrous feed and other products not suitable for human consumption. Substituting human edibles with by-products as feed for ruminants substantially increase the net food production (human edible output minus human edible input) (Ertl et al., 2016). The aim of this study was to investigate the effects on feed intake and milk production when human-edible feeds as cereal grain and soy beans was completely substituted with different blends of by-products as sugar beet pulp, rape seed meal and distillers grains in a high quality forage diet.
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42.
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43.
  • Karlsson, Johanna, et al. (författare)
  • Replacing human-edible feed ingredients with by-products increases net food production efficiency in dairy cows
  • 2018
  • Ingår i: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302 .- 1525-3198. ; 101, s. 7146-7155
  • Tidskriftsartikel (refereegranskat)abstract
    • Global demand for food is increasing, and use of large amounts of potentially human-edible feedstuffs for dairy cows is an important concern. The present study examined whether feeding a by-product-based concentrate combined with high-quality grass silage to high-producing dairy cows affected feed intake and milk production compared with a conventional diet, as well as the effect on efficiency of human food production. In a changeover experiment with four 21-d periods, 24 dairy cows in mid-lactation were offered 9.6 kg of dry matter per day with 1 of 4 concentrates and highquality grass silage ad libitum. The control concentrate was based on cereal grain (wheat, oat, and barley) and soybean meal, whereas the 3 by-product-based concentrates contained sugar beet pulp in combination with mainly heat-treated rapeseed meal, distillers grain, or a mixture of both. All diets were formulated to be isoenergetic and isonitrogenous. The cows had 10-fold higher starch intake when fed the control diet than when fed the by-product-based concentrates. Silage intake (13 kg of dry matter/d) and milk production (33 kg of energy-corrected milk/d) were not affected by the change in diet. Therefore, replacing cereals and soybean meal with human-inedible by-products in a high-quality forage diet to dairy cows increased net food protein production substantially without lowering milk production.
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44.
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45.
  • Karlsson, Johanna, et al. (författare)
  • Whole-lactation feed intake, milk yield, and energy balance of Holstein and Swedish Red dairy cows fed grass-clover silage and 2 levels of byproduct-based concentrate
  • 2020
  • Ingår i: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302 .- 1525-3198. ; 103, s. 8922-8937
  • Tidskriftsartikel (refereegranskat)abstract
    • Ruminants can produce meat and milk from fibrous feed and byproducts not suitable for human consumption. However, high-yielding dairy cows are generally fed a high proportion of cereal grain and pulses, which could be consumed directly by humans. If high production of dairy cows could be maintained with ingredients of low human interest, the sustainability of dairy production would improve. In the present study, 37 multiparous [Holstein (n = 13) and Swedish Red (n = 24)] dairy cows were followed over a whole lactation. A low-concentrate diet of up to 6 kg concentrate per day (6kgConc) was fed to 27 cows, whereas 10 cows were fed a high-concentrate diet of up to 12 kg concentrate per day (12kgConc). The concentrate was mainly based on byproducts (sugar beet pulp, wheat bran, rapeseed meal, distiller's grain). Grass-clover silage of high digestibility was offered ad libitum. Over the whole lactation, cows on the 6kgConc diet had lower dry matter intake and higher forage intake than cows on the 12kgConc diet. Milk yield and energy balance were not influenced by dietary treatment. However, the cows on the 6kgConc diet numerically produced 2.4 kg less energy-corrected milk than cows on 12kgConc diet. The study lacked the statistical power to identify treatment effects on daily yield below 2.8 kg of milk due to low number of animals per treatment. Feed efficiency (as energy-corrected milk yield/dry matter intake or residual feed intake), body weight change, body condition change, milk fatty acid concentration in total milk fatty acids, plasma nonesterified fatty acids, glucose, beta-hydroxybutyrate, and fertility measurements were not affected by diet, supporting the energy balance results. However, higher plasma concentrations o f insulin-like growth factor-1 and insulin were observed in cows fed he 12kgConc diet. These findings show that cows can adapt to a high-forage diet virtually without humangrade ingredients, without compromising feed efficiency or energy balance, thereby contributing to sustainable food production.
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46.
  • Karlsson Sundbaum, Johanna, et al. (författare)
  • Uncontrolled asthma predicts severe COVID-19: a report from the Swedish National Airway Register.
  • 2022
  • Ingår i: Therapeutic advances in respiratory disease. - : SAGE Publications. - 1753-4666 .- 1753-4658. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe asthma increases the risk of severe COVID-19 outcomes such as hospitalization and death. However, more studies are needed to understand the association between asthma and severe COVID-19.A cohort of 150,430 adult asthma patients were identified in the Swedish National Airway Register (SNAR) from 2013 to December 2020. Data on body mass index, smoking habits, lung function, and asthma control test (ACT) were obtained from SNAR, and uncontrolled asthma was defined as ACT ⩽19. Patients with severe COVID-19 were identified following hospitalization or in death certificates based on ICD-10 codes U07.1 and U07.2. The Swedish Prescribed Drug register was used to identify comorbidities and data from Statistics Sweden for educational level. Multivariate logistic regression analyses were used to estimate associations with severe COVID-19.Severe COVID-19 was identified in 1067 patients (0.7%). Older age (OR=1.04, 95% CI=1.03-1.04), male sex (1.42, 1.25-1.61), overweight (1.56, 1.27-1.91), obesity (2.12, 1.73-2.60), high-dose inhaled corticosteroids in combination with long-acting β-agonists (1.40, 1.22-1.60), dispensed oral corticosteroids ⩾2 (1.48, 1.25-1.75), uncontrolled asthma (1.64, 1.35-2.00), cardiovascular disease (1.20, 1.03-1.40), depression (1.47, 1.28-1.68), and diabetes (1.52, 1.29-1.78) were associated with severe COVID-19, while current smoking was inversely associated (0.63, 0.47-0.85). When comparing patients who died from COVID-19 with those discharged alive from hospital until 31 December 2020, older age, male sex, and current smoking were associated with COVID-19 death.Patients with uncontrolled asthma and high disease burden, including increased asthma medication intensity, should be identified as risk patients for severe COVID-19. Furthermore, current smoking is strongly associated with COVID-19 death in asthma.
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47.
  • Lindberg, Hanna, et al. (författare)
  • Are Farming and Animal Exposure Risk Factors for the Development of Granulomatosis with Polyangiitis? Environmental Risk Factors Revisited : A Case-control Study
  • 2021
  • Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 48:6, s. 894-897
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To investigate the possible association between animal exposure and risk for granulomatosis with polyangiitis (GPA).Methods. Patients with GPA at the Department of Rheumatology, Uppsala University Hospital, between January 1, 2011, and December 31, 2018, were consecutively included. All patients filled in a questionnaire on possible environmental exposures: occupation, hobbies, and animal contact. As controls we included 128 patients with rheumatoid arthritis (RA) and 248 population controls collected from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, matched for age, sex, and geographical area of residence. The controls filled out a questionnaire on current and past contact with farming and animals, at the time of the RA patient’s diagnosis.Results. A total of 62 patients with GPA, 128 patients with RA, and 248 population controls were included in the study. GPA was significantly associated with horse exposure, with a 2- to 3-fold increased risk compared with RA (OR 3.08, 95% CI 1.34–7.08) and population controls (OR 2.61, 95% CI 1.29–5.29). Borderline increased risks were found for any animal contact, but no association was found when analyzing contact with cats/dogs only. A significant association was found between GPA and farming compared to the population controls (OR 7.60, 95% CI 3.21–17.93).Conclusion. This study has identified for the first time, to our knowledge, a significant association between exposure to specific animals, namely horses, and the development of GPA. The results also support previous studies reporting an association between farming and GPA, underscoring the possibility of exogenous factors as initiators in the development of GPA.
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48.
  • Lindberg, Johanna, et al. (författare)
  • Bridging the Gap. Policies to Accelerate Social Change for an Inclusive Rural Digital Transformation in Sweden
  • 2024
  • Ingår i: European Countryside. - : Walter de Gruyter. - 1803-8417. ; 16:1, s. 26-42
  • Tidskriftsartikel (refereegranskat)abstract
    • This study explores officials' perspectives on Swedish policies for rural digital transformation (RDT). Through the lens of Social Acceleration and systems thinking, employing Critical Systems Heuristics collecting empirical data, we explore how officials perceive that Swedish digitalisation policies impacts inclusive RDT. We investigate whether the possibility to implement Swedish digitalisation policies support or hinder inclusive RDT. Our results emphasize the importance of Social Acceleration based on the aspirations of rural residents, encompassing technical acceleration, social change, and the pace of life. The rapid societal acceleration driven by digitalisation impacts the implementation of digital services in rural areas. Policies do not address the needs of tailored digital services; officials strive to manage this through creative methods despite inherent challenges.
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49.
  • Lindberg, Jonatan, et al. (författare)
  • En spark i baken för ett aktivare liv
  • 2011
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Efter årtionden av inaktivitet fick några patienter i 60-årsåldern fysisk aktivitet på recept (FaR). Vår studie pekar på att det var ett bra sätt att hjälpa dem att finna motivation och att ta ett första steg mot ett aktivare liv.
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50.
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