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1.
  • Schepke, Elizabeth, et al. (författare)
  • DNA methylation profiling improves routine diagnosis of paediatric central nervous system tumours: A prospective population-based study
  • 2022
  • Ingår i: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 48:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Paediatric brain tumours are rare, and establishing a precise diagnosis can be challenging. Analysis of DNA methylation profiles has been shown to be a reliable method to classify central nervous system (CNS) tumours with high accuracy. We aimed to prospectively analyse CNS tumours diagnosed in Sweden, to assess the clinical impact of adding DNA methylation-based classification to standard paediatric brain tumour diagnostics in an unselected cohort. Methods: All CNS tumours diagnosed in children (0-18 years) during 2017-2020 were eligible for inclusion provided sufficient tumour material was available. Tumours were analysed using genome-wide DNA methylation profiling and classified by the MNP brain tumour classifier. The initial histopathological diagnosis was compared with the DNA methylation-based classification. For incongruent results, a blinded re-evaluation was performed by an experienced neuropathologist. Results: Two hundred forty tumours with a histopathology-based diagnosis were profiled. A high-confidence methylation score of 0.84 or more was reached in 78% of the cases. In 69%, the histopathological diagnosis was confirmed, and for some of these also refined, 6% were incongruent, and the re-evaluation favoured the methylation-based classification. In the remaining 3% of cases, the methylation class was non-contributory. The change in diagnosis would have had a direct impact on the clinical management in 5% of all patients. Conclusions: Integrating DNA methylation-based tumour classification into routine clinical analysis improves diagnostics and provides molecular information that is important for treatment decisions. The results from methylation profiling should be interpreted in the context of clinical and histopathological information.
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  • Allard, Anna, et al. (författare)
  • Skador på mark och vegetation i de svenska fjällen till följd av barmarkskörning.
  • 2004
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • It is known that driving of all-terrain vehicles during summer in can cause damage to both vegetation and the underlying ground. However, in the mountainous parts of Sweden it is poorly known if these problems are of general nature or occurring in patches. The aim with this study was to make a general investigation into occurrences of vehicle-tracks in the Swedish mountainous areas and adjoining sparse forests, using field investigations, interpretation of color infrared aerial photos and a questionnaire survey. A field survey was carried out at 28 permanent plots of 1 x 1 km by personnel of the NILS (National Inventory of Landscapes in Sweden) program during the summer of 2003 and in 8 of the plots (28 %), vehicle tracks were found. Two of the 8 plots have been interpreted in color infrared aerial photos as a larger area of 5 x 5 km and a multitude of linear elements were found. From field control of the interpretations we can conclude that many of the linear elements visible from the air, are very hard to see at ground level. The questionnaire survey shows that vehicle tracks occur scattered over the mountainous area and also that 4-wheeled motorcycles are the dominant type of vehicle. The answers also show that tracks stay long on the ground and can be seen long after vegetation covers the initial damage.
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4.
  • Andersson, David, 1979, et al. (författare)
  • Attitudes to Personal Carbon Allowances
  • 2011
  • Ingår i: WORKING PAPERS IN ECONOMICS. - 1403-2465. ; 505
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • A personal carbon allowance (PCA) scheme targets emissions from individual consumption and allocates allowances directly to individuals by dividing the carbon budget on a per capita basis. In this study we analyze the results of a survey sent out to a representative sample of the Swedish population regarding attitudes to a potential PCA scheme. The distinctive design of a PCA scheme is likely to give rise to specific factors affecting individuals‟ attitudes, such as the perceived fairness of the allocation of allowances and corresponding redistribution of wealth, as well as the perceived complexity of the scheme. We perform an ordered probit analysis with attitude to PCAs as the dependent variable, controlling for a number of variables potentially affecting such attitudes. Interestingly, our findings indicate that the most important variable explaining attitudes to the scheme is the perception of respondents that this type of policy instrument seems very complex.
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6.
  • Arvidsson, Anna, 1973, et al. (författare)
  • Characterisation of structures in salivary secretion film formation. An experimental study with atomic force microscopy
  • 2004
  • Ingår i: Biofouling. - : Informa UK Limited. - 0892-7014 .- 1029-2454. ; 20:3, s. 181-8
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of the present study was to characterise the structure dynamics of pure salivary secretions retained on controlled surfaces with different surface energies in the early stage of salivary film formation. Germanium prisms prepared to have either low surface energy or medium surface energy were incubated in fresh secretions of either human parotid saliva (HPS) or human submandibular/sublingual saliva (HSMSLS) for 15, 90, and 180 min. After controlled rinsing with distilled water, the surfaces were air dried and thereafter imaged with atomic force microscopy (AFM). The amount of adsorbed material and the size of the structures detected increased with increased saliva exposure time. The film thicknesses varied from 10 to 150 nm, and both HPS and HSMSLS films contained structures with diameters varying from 40 nm to 2 microm. Some of these were clustered into special formations. The HPS films exhibited a more granular morphology than the HSMSLS films. Furthermore, branched lines were detected on the low surface energy germanium prisms incubated in saliva. The results indicate that exposure time, surface energy, and type of salivary secretion all are factors affecting the adsorption characteristics of salivary films.
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  • Bergman, Marie-Louise, et al. (författare)
  • CTLA-4-/- mice display T cell-apoptosis resistance resembling that ascribed to autoimmune-prone non-obese diabetic (NOD) mice
  • 2001
  • Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 16:2, s. 105-113
  • Tidskriftsartikel (refereegranskat)abstract
    • The genes conferring susceptibility to autoimmune (insulin-dependent) diabetes mellitus (IDDM) are, in most cases, not defined. Among the loci so far identified as associated with murine IDDM (Idd1-19), only the nature of Idd1 has been assessed. Here we show that thymocytes and peripheral lymphocytes of the non-obese diabetic (NOD) mouse are relatively resistant to apoptosis induced by gamma-irradiation. By linkage analysis of F2 progeny mice, we map this trait to a locus on chromosome 1 containing the Idd5 diabetes susceptibility region. By the use of congenic mice, we confirm the linkage data and map this locus to a 6 cM region on proximal chromosome 1. Ctla4, being localized in this chromosomal region and mediating crucial functions in T cell biology, is a logical candidate gene in the Idd5 susceptibility region. In line with this, we demonstrate that T cells from Ctla4(-/-)deficient mice show a similar resistance to gamma-irradiation-induced apoptosis as observed in the NOD mice. This reinforces the notion that CTLA-4 contributes to the pathogenesis of autoimmune diabetes.
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9.
  • Bodén, Stina, et al. (författare)
  • C-reactive Protein and Future Risk of Clinical and Molecular Subtypes of Colorectal Cancer
  • 2020
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:7, s. 1482-1491
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Inflammation has been implicated in colorectal cancer etiology, but the relationship between C-reactive protein (CRP) and colorectal cancer risk is unclear. We aimed to investigate the association between prediagnostic plasma CRP concentrations and the risk of clinical and molecular colorectal cancer subtypes.Methods: We used prospectively collected samples from 1,010 matched colorectal cancer case-control pairs from two population-based cohorts in Northern Sweden, including 259 with repeated samples. Conditional logistic regression and linear mixed models were used to estimate relative risks of colorectal cancer, including subtypes based on BRAF and KRAS mutations, microsatellite instability status, tumor location, stage, lag time, and (using unconditional logistic regression) body mass index.Results: CRP was not associated with colorectal cancer risk, regardless of clinical or molecular colorectal cancer subtype. For participants with advanced tumors and blood samples <5 years before diagnosis, CRP was associated with higher risk [OR per 1 unit increase in natural logarithm (In) transformed CRP, 1.32; 95% confidence interval (CI), 1.01-1.73]. CRP levels increased over time, but average time trajectories were similar for cases and controls (P-interaction = 0.19).Conclusions: Our results do not support intertumoral heterogeneity as an explanation for previous inconsistent findings regarding the role of CRP in colorectal cancer etiology. The possible association in the subgroup with advanced tumors and shorter follow-up likely reflects undiagnosed cancer at baseline. Impact: Future efforts to establish the putative role of chronic, low-grade inflammation in colorectal cancer development will need to address the complex relationship between systemic inflammatory factors and tumor microenvironment, and might consider larger biomarker panels than CRP alone.
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10.
  • Bodén, Stina, et al. (författare)
  • Plasma concentrations of gut hormones acyl ghrelin and peptide YY and subsequent risk of colorectal cancer and molecular tumor subtypes
  • 2023
  • Ingår i: Cancer Prevention Research. - : American Association for Cancer Research. - 1940-6207 .- 1940-6215. ; 16:2, s. 75-87
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity and metabolic dysfunction are implicated in colorectal cancer development. Appetite-regulating gut hormones might have a role in colorectal cancer risk. We investigated whether circulating levels of the gut hormones ghrelin (analyzed as acyl ghrelin) and Peptide YY (PYY) were associated with subsequent colorectal cancer risk, including clinical and molecular tumor subtypes. We also provide descriptive data on these hormones in relation to background participant characteristics and metabolic biomarkers. This population-based study included 1,010 matched case-control pairs with a median of 12.3 years of follow-up. Acyl ghrelin and PYY were measured by multiplex immunoassay. Data on KRAS and BRAF mutations and microsatellite instability (MSI) status were available for 704 and 708 cases, respectively. Conditional logistic regression models estimated association to colorectal cancer risk. Partial correlation and linear regression were used to investigate relationships between background and metabolic variables and variation in plasma gut hormone concentrations. Acyl ghrelin was not clearly associated with colorectal cancer risk (multivariable OR per 1 SD increase: 1.11; 95% CI, 1.00-1.23). Positive associations were observed for specific subtypes, in particular BRAF-mutated colorectal cancer and right-sided colon cancer, although with nonsignificant heterogeneity. PYY was not related to colorectal cancer risk (multivariable OR per 1 SD: 1.04; 95% CI, 0.95-1.14) or any tumor subtype. In the control participants, ghrelin was inversely correlated with BMI, and PYY was positively correlated with C-peptide and insulin levels. These findings provide limited support for a possible role for ghrelin in colorectal cancer development, primarily in specific anatomical and molecular tumor subtypes.PREVENTION RELEVANCE: The findings of this study do not support a major role for the metabolic gut hormones ghrelin and PYY in colorectal cancer development but suggest the possibility of an involvement for ghrelin in specific tumor subtypes. Elucidating subtype-specific risk factors and mechanisms of carcinogenesis may have implications for precision prevention.
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11.
  • Böös, Malin, et al. (författare)
  • Who should record surgical complications? : Results from a third-party assessment of complications after radical cystectomy
  • 2019
  • Ingår i: Scandinavian journal of urology. - : Informa Healthcare. - 2168-1805 .- 2168-1813. ; 53:5, s. 339-343
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: In Sweden complications after radical cystectomy have been reported to the nationwide population-based Swedish Cystectomy Registry since 2011. Here, validation of the reporting was assessed in two healthcare regions.Materials and methods: Complications were ascertained from patient records by a third party not involved in the care delivered to 429 randomly selected patients from 949 who had undergone radical cystectomy since 2011 in four hospitals. Without knowledge of the outcome in the primary registration, post-operative complications within 90 days post-operatively were assessed by an independent review of patient charts, and the results were compared with the primary reports in the Swedish Cystectomy Registry.Results: The third-party assessment identified post-operative complications in 310 patients (72%). Low-grade complications (Clavien-Dindo I-II) were noted in 110 (26%) of the patients in the primary registration, but increased to 182 (42%) in the validation (p < 0.00001). High-grade complications (Clavien-Dindo III-V) were reported in 113 (26%) patients in the primary registration, but in 128 (30%) of the patients in the validation (p = 0.02). According to the third-party assessment, 18 patients (4%) had Clavien-Dindo grade IV complications and 12 (3%) died within 90 days of surgery (Clavien-Dindo grade V); corresponding values in the primary registration were 15 (3%) and 9 (2%), respectively. The readmission rate within 90 days increased from 27 to 32% in the validation (p < 0.00001).Conclusions: Compared with registry data, third-party assessment revealed more complications and readmissions after radical cystectomy. Hence such evaluation may improve the validity of reported complication data.
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  • Costa, Raquel, et al. (författare)
  • Regional differences in the quality of maternal and neonatal care during the COVID-19 pandemic in Portugal : Results from the IMAgiNE EURO study
  • 2022
  • Ingår i: International Journal of Gynecology and Obstetrics. - : Wiley. - 0020-7292 .- 1879-3479. ; 159:S1, s. 137-153
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To compare women's perspectives on the quality of maternal and newborn care (QMNC) around the time of childbirth across Nomenclature of Territorial Units for Statistics 2 (NUTS-II) regions in Portugal during the COVID-19 pandemic. Methods: Women participating in the cross-sectional IMAgiNE EURO study who gave birth in Portugal from March 1, 2020, to October 28, 2021, completed a structured questionnaire with 40 key WHO standards-based quality measures. Four domains of QMNC were assessed: (1) provision of care; (2) experience of care; (3) availability of human and physical resources; and (4) reorganizational changes due to the COVID-19 pandemic. Frequencies for each quality measure within each QMNC domain were computed overall and by region. Results: Out of 1845 participants, one-third (33.7%) had a cesarean. Examples of high-quality care included: low frequencies of lack of early breastfeeding and rooming-in (8.0% and 7.7%, respectively) and informal payment (0.7%); adequate staff professionalism (94.6%); adequate room comfort and equipment (95.2%). However, substandard practices with large heterogeneity across regions were also reported. Among women who experienced labor, the percentage of instrumental vaginal births ranged from 22.3% in the Algarve to 33.5% in Center; among these, fundal pressure ranged from 34.8% in Lisbon to 66.7% in Center. Episiotomy was performed in 39.3% of noninstrumental vaginal births with variations between 31.8% in the North to 59.8% in Center. One in four women reported inadequate breastfeeding support (26.1%, ranging from 19.4% in Algarve to 31.5% in Lisbon). One in five reported no exclusive breastfeeding at discharge (22.1%; 19.5% in Lisbon to 28.2% in Algarve). Conclusion: Urgent actions are needed to harmonize QMNC and reduce inequities across regions in Portugal.
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14.
  • de Dios, Eddie, 1987, et al. (författare)
  • Comparison of the patient-derived modified Japanese Orthopaedic Association scale and the European myelopathy score
  • 2024
  • Ingår i: European Spine Journal. - : SPRINGER. - 0940-6719 .- 1432-0932. ; 33:3, s. 1205-1212
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To compare the patient-derived modified Japanese Orthopaedic Association (P-mJOA) scale with the European myelopathy score (EMS) for the assessment of patients with degenerative cervical myelopathy (DCM). Methods: In this register-based cohort study with prospectively collected data, included patients were surgically treated for DCM and had reported both P-mJOA and EMS scores at baseline, 1-year follow-up, and/or 2-year follow-up to the Swedish Spine Register. P-mJOA and EMS scores were defined as severe (P-mJOA 0–11 and EMS 5–8), moderate (P-mJOA 12–14 and EMS 9–12), or mild (P-mJOA 15–18 and EMS 13–18). P-mJOA and EMS mean scores were compared, and agreement was evaluated with Spearman’s rank correlation coefficient (ρ), the intraclass correlation coefficient (ICC), and kappa (κ) statistics. Results: Included patients (n = 714, mean age 63.2years, 42.2% female) completed 937 pairs of the P-mJOA and the EMS. The mean P-mJOA and EMS scores were 13.9 ± 3.0 and 14.5 ± 2.7, respectively (mean difference –0.61 [95% CI –0.72 to –0.51; p < 0.001]). Spearman’s ρ was 0.84 (p < 0.001), and intra-rater agreement measured with ICC was 0.83 (p < 0.001). Agreement of severity level measured with unweighted and weighted κ was fair (κ = 0.22 [p < 0.001]; κ = 0.34 [p < 0.001], respectively). Severity levels were significantly higher using the P-mJOA (p < 0.001). Conclusion: The P-mJOA and the EMS had similar mean scores, and intra-rater agreement was high, whereas severity levels only demonstrated fair agreement. The EMS has a lower sensitivity for detecting severe myelopathy but shows an increasing agreement with the P-mJOA for milder disease severity. A larger interval to define severe myelopathy with the EMS is recommended.
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15.
  • de Schipper, Elles, et al. (författare)
  • A comprehensive scoping review of ability and disability in ADHD using the International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY)
  • 2015
  • Ingår i: European Child and Adolescent Psychiatry. - : Springer. - 1018-8827 .- 1435-165X. ; 24:8, s. 859-872
  • Forskningsöversikt (refereegranskat)abstract
    • This is the first in a series of four empirical investigations to develop International Classification of Functioning, Disability and Health (ICF) Core Sets for Attention Deficit Hyperactivity Disorder (ADHD). The objective here was to use a comprehensive scoping review approach to identify the concepts of functional ability and disability used in the scientific ADHD literature and link these to the nomenclature of the ICF-CY. Systematic searches were conducted using Medline/PubMed, PsycINFO, ERIC and Cinahl, to extract the relevant concepts of functional ability and disability from the identified outcome studies of ADHD. These concepts were then linked to ICF-CY by two independent researchers using a standardized linking procedure. Data from identified studies were analysed until saturation of ICF-CY categories was reached. Eighty studies were included in the final analysis. Concepts contained in these studies were linked to 128 ICF-CY categories. Of these categories, 68 were considered to be particularly relevant to ADHD (i.e., identified in at least 5 % of the studies). Of these, 32 were related to Activities and participation, 31 were related to Body functions, and five were related to environmental factors. The five most frequently identified categories were school education (53 %), energy and drive functions (50 %), psychomotor functions (50 %), attention functions (49 %), and emotional functions (45 %). The broad variety of ICF-CY categories identified in this study underlines the necessity to consider ability and disability in ADHD across all dimensions of life, for which the ICF-CY provides a valuable and universally applicable framework. These results, in combination with three additional preparatory studies (expert survey, focus groups, clinical study), will provide a scientific basis to define the ICF Core Sets for ADHD for multi-purpose use in basic and applied research, and every day clinical practice.
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  • Drandić, Daniela, et al. (författare)
  • Women's perspectives on the quality of hospital maternal and newborn care around the time of childbirth during the COVID-19 pandemic : Results from the IMAgiNE EURO study in Slovenia, Croatia, Serbia, and Bosnia-Herzegovina
  • 2022
  • Ingår i: International Journal of Gynecology and Obstetrics. - : Wiley. - 0020-7292 .- 1879-3479. ; 159:S1, s. 54-69
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To assess the quality of maternal and newborn care (QMNC) in countries of the former Yugoslavia. Method: Women giving birth in a facility in Slovenia, Croatia, Serbia, and Bosnia-Herzegovina between March 1, 2020 and July 1, 2021 answered an online questionnaire including 40 WHO standards-based quality measures. Results: A total of 4817 women were included in the analysis. Significant differences were observed across countries. Among those experiencing labor, 47.4%–62.3% of women perceived a reduction in QMNC due to the COVID-19 pandemic, 40.1%–69.7% experienced difficulties in accessing routine antenatal care, 60.3%–98.1% were not allowed a companion of choice, 17.4%–39.2% reported that health workers were not always using personal protective equipment, and 21.2%–53.8% rated the number of health workers as insufficient. Episiotomy was performed in 30.9%–62.8% of spontaneous vaginal births. Additionally, 22.6%–55.9% of women received inadequate breastfeeding support, 21.5%–62.8% reported not being treated with dignity, 11.0%–30.5% suffered abuse, and 0.7%–26.5% made informal payments. Multivariate analyses confirmed significant differences among countries, with Slovenia showing the highest QMNC index, followed by Croatia, Bosnia-Herzegovina, and Serbia. Conclusion: Differences in QMNC among the countries of the former Yugoslavia during the COVID-19 pandemic were significant. Activities to promote high-quality, evidence-based, respectful care for all mothers and newborns are urgently needed. ClinicalTrials.gov Identifier: NCT04847336.
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  • Edin, Sofia, et al. (författare)
  • Opposing roles by KRAS and BRAF mutation on immune cell infiltration in colorectal cancer : possible implications for immunotherapy
  • 2024
  • Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 130
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The immune response has important clinical value in colorectal cancer (CRC) in both prognosis and response to immunotherapy. This study aims to explore tumour immune cell infiltration in relation to clinically well-established molecular markers of CRC.Methods: Multiplex immunohistochemistry and multispectral imaging was used to evaluate tumour infiltration of cytotoxic T cells (CD8+), Th1 cells (T-bet+), T regulatory cells (FoxP3+), B cells (CD20+), and macrophages (CD68+) in a cohort of 257 CRC patients.Results: We found the expected association between higher immune-cell infiltration and microsatellite instability. Also, whereas BRAF-mutated tumours displayed increased immune-cell infiltration compared to BRAF wild-type tumours, the opposite was seen for KRAS-mutated tumours, differences that were most prominent for cytotoxic T cells and Th1 cells. The opposing relationships of BRAF and KRAS mutations with tumour infiltration of cytotoxic T cells was validated in an independent cohort of 608 CRC patients. A positive prognostic importance of cytotoxic T cells was found in wild-type as well as KRAS and BRAF-mutated CRCs in both cohorts.Conclusion: A combined evaluation of MSI status, KRAS and BRAF mutational status, and immune infiltration (cytotoxic T cells) may provide important insights to prognosis and response to immunotherapy in CRC.
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  • Einarsdottir, Elisabet, et al. (författare)
  • The CTLA4 region as a general autoimmunity factor: an extended pedigree provides evidence for synergy with the HLA locus in the etiology of type 1 diabetes mellitus, Hashimoto's thyroiditis and Graves' disease
  • 2003
  • Ingår i: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 11:1, s. 81-84
  • Tidskriftsartikel (refereegranskat)abstract
    • We have identified a large family in the northern part of Sweden with multiple cases of autoimmune diseases, namely type 1 diabetes (T1D), Graves' disease (GD) and Hashimoto's thyroiditis (HT). The family members affected by any of these diseases share a region of 2.4 Mb that comprises among others the CTLA4 gene. We determined that all affected members of the family shared the HLA susceptibility haplotype (DR4-DQA1*0301-DQB1*0302). Analysis of genetic interaction conditioning for HLA haplotype provided strong evidence that the critical region which includes the CTLA4 gene acts together with the HLA locus on the etiology of disease (lodscore 4.20 (theta=0.0). The study of this family allowed us to: (1) reinforce a number of reports on linkage and association of the CTLA4 region to T1D and AITD; (2) demonstrate that a single haplotypic variant in this region constitutes an etiological factor to disease susceptibility in T1D, GD and HT; (3) reveal a strong genetic interaction of the CTLA4 and HLA loci in the genetic architecture of autoimmune disease; (4) emphasise the value of large pedigrees drawn from isolated populations as tools to single out the effect of individual loci in the etiology of complex diseases.
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21.
  • Ekbäck, Erik, et al. (författare)
  • Training for Awareness, Resilience and Action (TARA) for medical students : a single-arm mixed methods feasibility study to evaluate TARA as an indicated intervention to prevent mental disorders and stress-related symptoms
  • 2022
  • Ingår i: BMC Medical Education. - : BioMed Central (BMC). - 1472-6920. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Medical students have a higher risk for depression, anxiety, stress-related symptoms, burnout, and suicide, and more rarely seek professional help or treatment than the general population. Appeals are being made to address the mental health and resilience of physicians-to-be. The novel program Training for Awareness, Resilience, and Action (TARA) was originally developed to treat depressed adolescents, targeting specific neuroscientific findings in this population. TARA has shown feasibility and preliminary efficacy in clinically depressed adolescents and corresponding brain-changes in mixed community adolescent samples. The present study investigated the feasibility and acceptability of TARA as a potential indicated prevention program for symptoms of depression, anxiety, stress and burnout in Swedish medical students.Methods: We conducted a single-arm trial with 23 self-selected students in their early semesters of medical school (mean age 25.38 years, 5 males and 18 females), with or without mental disorders. All participants received TARA. Self-reported symptoms of depression, anxiety, perceived stress and psychological inflexibility were collected before (T0) and after the intervention (T1). Qualitative data on the participants’ experiences of TARA were collected in focus-group interviews conducted halfway through the program and upon completion of the program. Individual interviews were also conducted 2 years later. Qualitative content analysis was performed.Results: The mean attendance rate was 61.22% and the dropout rate was 17.40%. The Child Session Rating Scale administered after every session reflected an overall acceptable content, mean total score 34.99 out of 40.00. Trends towards improvement were seen across all outcome measures, including the Hospital Anxiety and Depression Scale Anxiety (t = 1.13, p = 0.29) and Depression (t = 1.71, p = 0.11) subscales, Perceived Stress Scale (t = 0.67, p = 0.51) and Avoidance and Fusion Questionnaire for youth (t = 1.64, p = 0.10). None of the participants deteriorated markedly during the intervention. Qualitative content analysis resulted in a main theme labeled: “An uncommon meeting-ground for personal empowerment”, with 4 themes; “Acknowledging unmet needs”, “Entering a free zone”, “Feeling connected to oneself and others” and “Expanding self-efficacy”.Conclusion: TARA is feasible and acceptable in a mixed sample of Swedish medical students. The students’ reports of entering an uncommon meeting-ground for personal empowerment supports effectiveness studies of TARA in this context.
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22.
  • Eklöf, Vincy, 1984-, et al. (författare)
  • Cancer-associated fecal microbial markers in colorectal cancer detection
  • 2017
  • Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 141:12, s. 2528-2536
  • Tidskriftsartikel (refereegranskat)abstract
    • Colorectal cancer (CRC) is the second most common cause of cancer death in the western world. An effective screening program leading to early detection of disease would severely reduce the mortality of CRC. Alterations in the gut microbiota have been linked to CRC, but the potential of microbial markers for use in CRC screening has been largely unstudied. We used a nested case-control study of 238 study subjects to explore the use of microbial markers for clbA+ bacteria harboring the pks pathogenicity island, afa-C+ diffusely adherent Escherichia coli harboring the afa-1 operon, and Fusobacterium nucleatum in stool as potential screening markers for CRC. We found that individual markers for clbA+ bacteria and F. nucleatum were more abundant in stool of patients with CRC, and could predict cancer with a relatively high specificity (81.5% and 76.9%, respectively) and with a sensitivity of 56.4% and 69.2%, respectively. In a combined test of clbA+ bacteria and F. nucleatum, CRC was detected with a specificity of 63.1% and a sensitivity of 84.6%. Our findings support a potential value of microbial factors in stool as putative noninvasive biomarkers for CRC detection. We propose that microbial markers may represent an important future screening strategy for CRC, selecting patients with a "high-risk" microbial pattern to other further diagnostic procedures such as colonoscopy.
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24.
  • Eklöf, Vincy, 1984-, et al. (författare)
  • The Combined Value of Faecal Haemoglobin andCalprotectin in Diagnosis of Colorectal Cancer inSymptomatic Patients Referred to Colonoscopy
  • 2019
  • Ingår i: Academic Journal of Gastroenterology & Hepatology (AJGH). - San Fransisco : Iris Publishers. ; 1:3, s. 1-7
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Aim: To investigate the diagnostic value of a combined analyses of faecal immunological haemoglobin (FIT) and faecal calprotectin (FC) in detection of colorectal cancer (CRC).Methods: Out-patients (n=1440) referred to the endoscopy unit were analysed for FIT and FC in stool samples collected before the colonoscopy bowel preparation. The samples were collected from one defecation by the patients at home. Patients with IBD were excluded leaving stool samples from 1133 patients for further analyses. FIT was analysed using the immunological Analyse F.O.B Test and FC was analysed using the CALPRO® Calprotectin Elisa Test. Sensitivity and specificity to detect CRC was calculated for the individual tests, as well as for combined FIT/FC tests.Results: Out of the included patients, 38 were diagnosed with CRC, 9 with high grade dysplasia (HGD), and 133 with low grade dysplasia (LGD). FIT was analysed in 673 (59.4%), FC in 1021 (90.1%) and both FIT and FC in 561 (49.5%) patients. A ROC curve analysis showed that the most accurate cut-off level for FC in detecting CRC in our study was 105.5 µg/g. The sensitivity for CRC when using FIT, FC (cut-off > 100 µg/g) and the combination of FIT and FC (at least one positive test) was 65.5%, 74.1% and 94.4%, respectively. The corresponding specificity was 84.8%, 74.9% and 68.3%, respectively.Conclusion: Combined analyses of FIT and FC improved sensitivity for detection of CRC. Further studies in larger cohorts are required to find the optimal cut-off levels for different combinations of tests.
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25.
  • Ekman, Stina, et al. (författare)
  • Effect of circadian rhythm, age, training and acute lameness on serum concentrations of cartilage oligomeric matrix protein (COMP) neo-epitope in horses
  • 2019
  • Ingår i: Equine Veterinary Journal. - : Wiley. - 0425-1644 .- 2042-3306. ; 51:5, s. 674-680
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Molecular serum markers that can identify early reversible osteoarthritis (OA) in horses are lacking. Objectives We studied serum concentrations of a novel cartilage oligomeric matrix protein (COMP) neo-epitope in horses subjected to short-term exercise and with acute lameness. The effects of circadian rhythm and age were also evaluated. Study design Longitudinal studies in healthy horses and cross-sectional comparison of lame and non-lame horses. Methods Sera were collected from five horses before and after short-term interval exercise and during full-day box rest. Sera from 32 acutely lame horses were used to evaluate age-related effects. Independent samples from control horses (n = 41) and horses with acute lameness (n = 71) were included. COMP neo-epitope concentrations were analysed using custom-developed inhibition ELISAs validated for equine serum. The presence of COMP neo-epitope was delineated in healthy and osteoarthritic articular cartilage with immunohistochemistry. Results COMP neo-epitope concentrations decreased after speed training but returned to baseline levels post-exercise. No correlations between age and serum COMP neo-epitope concentrations were found (r = 0.0013). The mean (+/- s.d.) serum concentration of COMP neo-epitope in independent samples from non-lame horses was 0.84 +/- 0.38 mu g/mL, and for lame horses was 5.24 +/- 1.83 mu g/mL (P<0.001). Antibodies against COMP neo-epitope did not stain normal articular cartilage, but intracytoplasmic staining was found in superficial chondrocytes of mild OA cartilage and in the extracellular matrix of moderately osteoarthritic cartilage. Main limitations ELISA was based on polyclonal antisera rather than a monoclonal antibody. There is a sex and breed bias within the groups of horses, also it could have been of value to include horses with septic arthritis and tendonitis and investigated joint differences. Conclusions This COMP neo-epitope can be measured in sera, and results indicate that it could be a biomarker for pathologic fragmentation of cartilage in connection with acute joint lameness.
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26.
  • Ericsson, Anna, et al. (författare)
  • Resistance exercise improves physical fatigue in women with fibromyalgia : a randomized controlled trial.
  • 2016
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362. ; 18
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Fibromyalgia (FM) affects approximately 1-3 % of the general population. Fatigue limits the work ability and social life of patients with FM. A few studies of physical exercise have included measures of fatigue in FM, indicating that exercise can decrease fatigue levels. There is limited knowledge about the effects of resistance exercise on multiple dimensions of fatigue in FM. The present study is a sub-study of a multicenter randomized controlled trial in women with FM. The purpose of the present sub-study was to examine the effects of a person-centered progressive resistance exercise program on multiple dimensions of fatigue in women with FM, and to investigate predictors of the potential change in fatigue.METHODS: A total of 130 women with FM (age 22-64 years) were included in this assessor-blinded randomized controlled multicenter trial examining the effects of person-centered progressive resistance exercise compared with an active control group. The intervention was performed twice a week for 15 weeks. Outcomes were five dimensions of fatigue measured with the Multidimensional Fatigue Inventory (MFI-20). Information about background was collected and the women also completed several health-related questionnaires. Multiple linear stepwise regression was used to analyze predictors of change in fatigue in the total population.RESULTS: A higher improvement was found at the post-treatment examination for change in the resistance exercise group, as compared to change in the active control group in the MFI-20 subscale of physical fatigue (resistance group Δ -1.7, SD 4.3, controls Δ 0.0, SD 2.7, p = 0.013), with an effect size of 0.33. Sleep efficiency was the strongest predictor of change in the MFI-20 subscale general fatigue (beta = -0.54, p = 0.031, R (2) = 0.05). Participating in resistance exercise (beta = 1.90, p = 0.010) and working fewer hours per week (beta = 0.84, p = 0.005) were independent significant predictors of change in physical fatigue (R (2) = 0.14).CONCLUSIONS: Person-centered progressive resistance exercise improved physical fatigue in women with FM when compared to an active control group.TRIAL REGISTRATION: ClinicalTrials.gov NCT01226784 . Registered 21 October 2010.
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27.
  • Esberg, Anders, et al. (författare)
  • Host and bacterial phenotype variation in adhesion of streptococcus mutans to matched human hosts
  • 2012
  • Ingår i: Infection and Immunity. - Washington : American Society Microbiology. - 0019-9567 .- 1098-5522. ; 80:11, s. 3869-3879
  • Tidskriftsartikel (refereegranskat)abstract
    • The commensal pathogen Streptococcus mutans uses AgI/II adhesins to adhere to gp340 adsorbed on teeth. Here we analyzed isolates of S. mutans (n = 70 isolates) from caries and caries-free human extremes (n = 19 subjects) by multilocus sequence typing (MLST), AgI/II full-length gene sequencing, and adhesion to parotid saliva matched from the strain donors (nested from a case-control sample of defined gp340 and acidic proline-rich protein [PRP] profiles). The concatenated MLST as well as AgI/II gene sequences showed unique sequence types between, and identical types within, the subjects. The matched adhesion levels ranged widely (40% adhesion range), from low to moderate to high, between subjects but were similar within subjects (or sequence types). In contrast, the adhesion avidity of the strains was narrow, normally distributed for high, moderate, or low adhesion reference saliva or pure gp340 regardless of the sequence type. The adhesion of S. mutans Ingbritt and matched isolates and saliva samples correlated (r = 0.929), suggesting that the host specify about four-fifths (r(2) = 0.86) of the variation in matched adhesion. Half of the variation in S. mutans Ingbritt adhesion to saliva from the caries cases-controls (n = 218) was explained by the primary gp340 receptor and PRP coreceptor composition. The isolates also varied, although less so, in adhesion to standardized saliva (18% adhesion range) and clustered into three major AgI/II groups (groups A, B-1, and B-2) due to two variable V-region segments and diverse AgI/II sequence types due to a set of single-amino-acid substitutions. Isolates with AgI/II type A versus types B-1 and B-2 tended to differ in gp340 binding avidity and qualitative adhesion profiles for saliva gp340 phenotypes. In conclusion, the host saliva phenotype plays a more prominent role in S. mutans adhesion than anticipated previously.
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28.
  • Futter, Martyn, et al. (författare)
  • Forests, Forestry and the Water Framework Directive in Sweden : A Trans-Disciplinary Commentary
  • 2011
  • Ingår i: Forests. - : MDPI AG. - 1999-4907. ; 2:1, s. 261-282
  • Tidskriftsartikel (refereegranskat)abstract
    • The Water Framework Directive (WFD) is an ambitious piece of legislation designed to protect and improve water quality throughout Europe. However, forests are only mentioned once in the WFD, and forestry is not mentioned at all, despite its potential implications for streams, rivers and lakes. Here we present a transdisciplinary commentary on the WFD and its implications for forests and forestry in Sweden. This commentary has been prepared by forestry stakeholders, biophysical and social scientists. While we were cognizant of a large body of discipline-specific research, there are very few inter-or trans-disciplinary commentaries which link academic and stakeholder perspectives on the WFD. We had originally felt that there would be little commonality in our concerns. However, we found significant areas of agreement. Our key areas of concern about the implications of the WFD for forestry in Sweden included: (i) concerns about what is meant by good ecological status and how it is assessed; (ii) a perceived lack of clarity in the legal framework; (iii) an inadequate environmental impact assessment process; and (iv) uncertainties about appropriate programs of measures for improving water quality. We were also concerned that ecosystem services provided by forests and the positive effects of forestry on water quality are inadequately recognized in the WFD.
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29.
  • Glimskär, Anders, et al. (författare)
  • Uppföljning av naturvärden i ängs- och betesmarker via NILS : Statistisk utvärdering och förslag till design
  • 2005
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Denna rapport har som syfte att ge förslag till utformning av ett uppföljningssystem förnaturvärden i objekt som identifierats som skyddsvärda i Ängs- och betesmarksinventeringen(Jordbruksverket 2005a, b) samt göra en statistisk och kostnadsmässig utvärdering av olikadesignalternativ. Utgångspunkten har varit att uppföljningen ska ske i ett stickprov av objektsom så nära som möjligt ansluter till den metodik och de landskapsrutor som används i detnationella miljöövervakningsprogrammet NILS (Allard m.fl., 2003, Esseen m.fl., 2005). Avde åtta indikatorer som föreslagits av Naturcentrum (2004) har vi valt ut de fem som verkarmest lämpade för uppföljning i anslutning till NILS. Den metodik som föreslagits avNaturcentrum (2004) har följts så långt möjligt, men vissa modifieringar har gjorts för att görauppföljningen effektivare.
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30.
  • Gårdebjer, Sofie, 1985, et al. (författare)
  • Controlling water permeability of composite films of polylactide acid, cellulose, and xyloglucan
  • 2015
  • Ingår i: Journal of Applied Polymer Science. - : Wiley. - 1097-4628 .- 0021-8995. ; 132:1
  • Tidskriftsartikel (refereegranskat)abstract
    • To test the hypothesis that the introduction of a hydrophilic hemicellulose would affect viscoelastic properties and increase water permeability, xyloglucan (XG) was adsorbed onto the surface of microcrystalline cellulose (MCC) in water dispersion prior to the extrusion of 79–80 wt % polylactide acid (PLA), 20 wt % MCC, and 0–1 wt % XG. For comparison, composites of PLA, MCC, and non-absorbed XG were produced. Analysis of thermal properties showed no differences for glass-transition or melting temperatures, but the crystallinity of the films increased with the addition of MCC and XG. Storage modulus of the composite materials increased with XG content; however, at higher humidities storage modulus decreased, probably because of lower interfacial adhesion. Water permeability through the films increased more with the addition of XG adsorbed to the MCC than with the MCC and XG simply mixed in the same amounts.
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31.
  • Henningsson, Anna J., 1972-, et al. (författare)
  • Laboratory diagnosis of Lyme neuroborreliosis: a comparisonof three CSF anti-Borrelia antibody assays
  • 2014
  • Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Publishing Company. - 0934-9723 .- 1435-4373. ; 33, s. 797-803
  • Tidskriftsartikel (refereegranskat)abstract
    • The diagnosis of Lyme neuroborreliosis (LNB) requires the detection of intrathecal synthesis of Borrelia-specific antibodies, but in very early disease, the sensitivity may be low. We compared the performance of the second-generation IDEIA Lyme Neuroborreliosis test (Oxoid), based on purified native flagellum antigen, with two newly developed tests based on several recombinant antigens for the diagnosis of LNB. Patients investigated for LNB during 2003 through 2007 were included (n = 175); 52 with definite LNB, four with possible LNB and 119 non-LNB patients. Serum and cerebrospinal fluid (CSF) were analysed with the IDEIA Lyme Neuroborreliosis (Oxoid), VIDAS Lyme IgG (bioMérieux) and recomBead Borrelia IgM and IgG (Mikrogen) assays. Intrathecal antibody indices (AIs) were calculated according to the manufacturers’ protocols. The IDEIA test performed with an overall sensitivity (IgM and IgG AIs taken together) of 88 % and a specificity of 99 %. The VIDAS test showed a sensitivity of 86 % and a specificity of 97 %. An overall sensitivity of 100 % and a specificity of 97 % were achieved by the recomBead test. We conclude that the three assays performed equally well regarding specificity, but our data suggest an improved diagnostic sensitivity with the recomBead Borrelia test.
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32.
  • Hermansen, Anna, et al. (författare)
  • Dizziness and balance outcomes after two different postoperative rehabilitation approaches following neck surgery : analyses of a multicenter randomized controlled trial
  • 2023
  • Ingår i: Physiotherapy Theory and Practice. - Philadelphia, PA, United States : Taylor & Francis. - 0959-3985 .- 1532-5040. ; 39:4, s. 750-760
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Dizziness and balance problems are common symptoms in patients with cervical radiculopathy. Objective To evaluate the effect of neck surgery postoperatively combined with either structured rehabilitation or standard approach in patients with cervical radiculopathy and dizziness and/or balance problems, and investigate factors influencing dizziness and balance at 6-month follow-up.Methods Individuals (n = 149) with cervical radiculopathy and dizziness and/or balance problems were randomized preoperatively to structured postoperative rehabilitation or standard postoperative approach. Outcomes were intensity of dizziness and subjective balance, and clinical measures of balance.Results Self-reported measures improved at three months (p < 0.001 to p = .007) and the standing balance at six months (p = .008). No between-group differences. Baseline values, neck pain, and physical activity level explained 23-39% of the variance in 6-month outcomes for self-reported measures. Baseline values and physical activity level explained 71% of the variance in walking balance, and lower baseline scores were significantly associated with standing balance impairments (OR 0.876).Conclusion Patients improved significantly in dizziness and subjective balance intensity shortly after surgery, and in standing balance at 6 months, independent of postoperative rehabilitation. Neck pain, physical activity, and neck muscle function influenced dizziness and balance, although preoperative values and neck pain were of most importance for 6-month outcomes.
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33.
  • Holmqvist, Anna, et al. (författare)
  • Fatigue and cognitive fatigability in patients with chronic pain
  • 2024
  • Ingår i: Scandinavian Journal of Pain. - : Walter de Gruyter. - 1877-8860 .- 1877-8879. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Fatigue is common in patients with chronic pain. Still, there is a lack of studies examining objectively measurable cognitive aspects of fatigue: cognitive fatigability (CF). We aimed to investigate the presence of CF in patients with chronic pain and its relation to self-rated fatigue, attention, pain characteristics, sleep disturbance, depression, and anxiety.Methods: Two hundred patients with chronic pain and a reference group of 36 healthy subjects underwent a comprehensive neuropsychological test battery, including measurement of CF with the Wechsler Adult Intelligence Scale-III Coding subtest, and self-assessment of trait and state fatigue.Results: The patients with chronic pain did not show more CF as compared to the reference group. There was an association between CF and processing speed on a test of sustained and selective attention in the chronic pain group, while self-rated fatigue measures and pain characteristics were not associated with CF. Self-rated fatigue measures were highly correlated with self-rated pain intensity, spreading of pain, depression, anxiety, and sleep disturbance.Conclusions: The findings highlight the distinction between objective and subjective aspects of fatigue in chronic pain, and that the underlying causes of these different aspects of fatigue need to be studied further.
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34.
  • Hultsjö, Sally, et al. (författare)
  • Nurses experiences of suicide attempts in palliative care
  • 2023
  • Ingår i: Palliative & Supportive Care. - : CAMBRIDGE UNIV PRESS. - 1478-9515 .- 1478-9523.
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesTo describe nurses experiences of caring for individuals who have attempted suicide in specialized palliative care and to describe if the care of these individuals changed after the suicide attempt. MethodsA qualitative, descriptive study was conducted. Nine nurses working in specialized palliative care units were interviewed following a semi-structured interview guide. Conventional content analysis was used in the analysis process. ResultsThe results are presented in 3 categories: "A suicide attempt evokes strong emotions," "Health-care efforts changed after the suicide attempt," and "Experiences for the rest of working life." Suicide attempts aroused emotions in nurses such as frustration, compassion, and feelings of being manipulated. The relationship between the nurse and the individual was strengthened after the suicide attempt, and their conversations became deeper and changed in nature. Health-care efforts relating to the individual increased after the suicide attempt. Significance of resultsThe results of the study can create an awareness that the palliative process also includes the risk of suicide and can be used to create conditions for nurses to be able to handle questions about suicide without fear. The results of the study can be used as an "eye opener" to the fact that suicidality occurs in palliative care. In summary, there is a critical need for nursing education in suicide risk assessment and continued follow-up care for patients at risk of suicide within palliative care.
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35.
  • Jonsson, Ulf, 1974-, et al. (författare)
  • Annual Research Review : Quality of life and childhood mental and behavioural disorders - a critical review of the research.
  • 2017
  • Ingår i: Journal of Child Psychology and Psychiatry. - : Wiley. - 0021-9630 .- 1469-7610. ; 58:4, s. 439-469
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND: An individual's subjective perception of well-being is increasingly recognized as an essential complement to clinical symptomatology and functional impairment in children's mental health. Measurement of quality of life (QoL) has the potential to give due weight to the child's perspective.SCOPE AND METHODOLOGY: Our aim was to critically review the current evidence on how childhood mental disorders affect QoL. First, the major challenges in this research field are outlined. Then we present a systematic review of QoL in children and adolescents aged 0-18 years formally diagnosed with a mental and behavioural disorder, as compared to healthy or typically developing children or children with other health conditions. Finally, we discuss limitations of the current evidence base and future directions based on the results of the systematic review and other relevant literature.FINDINGS AND CONCLUSIONS: The systematic review identified 41 eligible studies. All were published after the year 2000 and 21 originated in Europe. The majority examined QoL in neurodevelopmental disorders, including attention-deficit hyperactivity disorder (k = 17), autism spectrum disorder (k = 6), motor disorders (k = 5) and intellectual disability (k = 4). Despite substantial heterogeneity, studies demonstrate that self-reported global QoL is significantly reduced compared to typical/healthy controls across several disorders and QoL dimensions. Parents' ratings were on average substantially lower, casting doubt on the validity of proxy-report. Studies for large diagnostic groups such as depressive disorders, anxiety disorders, (early onset) schizophrenia and eating disorders are largely lacking. We conclude that representative, well-characterized normative and clinical samples as well as longitudinal and qualitative designs are needed to further clarify the construct of QoL, to derive measures of high ecological validity, and to examine how QoL fluctuates over time and is attributable to specific conditions or contextual factors.
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36.
  • Kerdreux, Maïwenn, et al. (författare)
  • Porphyromonas gingivalis in colorectal cancer and its association to patient prognosis
  • 2023
  • Ingår i: Journal of Cancer. - : Ivyspring International Publisher. - 1837-9664. ; 14:9, s. 1479-1485
  • Tidskriftsartikel (refereegranskat)abstract
    • Microbiota dysbiosis may affect both the development and progression of colorectal cancer (CRC). Large metagenomic studies have highlighted specific oral bacteria linked to CRC including Porphyromonas gingivalis. Few studies have however analysed the implications of this bacterium in CRC progression and survival. In this study, we investigated the intestinal presence of P. gingivalis by qPCR in both faecal and mucosal samples from two different patient cohorts, including patients with precancerous dysplasia or CRC, as well as controls. P. gingivalis was detected in 2.6-5.3% of CRC patients and significantly different levels of P. gingivalis were found in faeces of CRC patients compared to controls (P = 0.028). Furthermore, an association was found between the presence of P. gingivalis in faeces and tumour tissue (P < 0.001). Our findings further suggested a potential link between mucosal P. gingivalis and tumours of MSI subtype (P = 0.040). Last but not least, patients with faecal P. gingivalis were found to have a significantly decreased cancer-specific survival (P = 0.040). In conclusion, P. gingivalis could be linked to patients with CRC and to a worse patient prognosis. Further studies are needed to elucidate the role of P. gingivalis in CRC pathogenesis.
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37.
  • Kontakis, Michael G., et al. (författare)
  • Artificial disc replacement and adjacent-segment pathology : 10-year outcomes of a randomized trial
  • 2022
  • Ingår i: Journal of Neurosurgery. - : AMER ASSOC NEUROLOGICAL SURGEONS. - 1547-5654 .- 1547-5646. ; 36:6, s. 945-953
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Artificial disc replacement (ADR) is designed to preserve motion and thus protect against adjacent-segment pathology (ASP) and act as an alternative treatment to fusion surgery. The question remains, how well do ADR devices perform after 10 years of follow-up compared with fusion surgery in terms of patient satisfaction, sustainability, and protection against ASP?METHODS: This was the 10-year follow-up study of 153 participants who underwent ADR or fusion surgery after anterior decompression due to cervical degenerative radiculopathy (ISRCTN registration no. 44347115). Scores on the Neck Disability Index (NDI), EQ-5D, and visual analog scale for neck and arm pain were obtained from the Swedish Spine Registry and analyzed using ANCOVA. Information about secondary surgical procedures was collected from medical records and presented as Kaplan-Meier curves. MRI and flexion-extension radiography were performed, and ASP was graded according to the Miyazaki classification system.RESULTS: Ten participants were lost to follow-up, which left 143 participants (80 underwent ADR and 65 underwent anterior cervical discectomy and fusion). There were no differences between groups in terms of patient-reported outcome measures (10-year difference in NDI scores 1.7 points, 95% CI -5.1 to 8.5, p = 0.61). Nineteen (24%) participants in the ADR group compared with 9 (14%) in the fusion group underwent secondary surgical procedures. The higher reoperation rate of the ADR group was mainly due to 11 female participants with device loosening. The rates of reoperation due to ASP were similar between groups, which was confirmed with MRI assessment of ASP that also showed no differences between the groups (p = 0.21).CONCLUSIONS: This was the first 10-year follow-up study to compare ADR with fusion surgery and to provide MRI information for the assessment of ASP. The authors found no benefit of ADR over fusion surgery after anterior decompression for cervical degenerative radiculopathy.
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38.
  • Li, Xingru, et al. (författare)
  • A Detailed Flow Cytometric Analysis of Immune Activity Profiles in Molecular Subtypes of Colorectal Cancer
  • 2020
  • Ingår i: Cancers. - : MDPI. - 2072-6694. ; 12:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The local anti-tumour immune response has important prognostic value in colorectal cancer (CRC). In the era of immunotherapy, a better understanding of the immune response in molecular subgroups of CRC may lead to significant advances in personalised medicine. On this note, microsatellite instable (MSI) tumours have been characterised by increased immune infiltration, suggesting MSI as a marker for immune inhibitor checkpoint therapy. Here, we used flow cytometry to perform a comprehensive analysis of immune activity profiles in tumour tissues, adjacent non-malignant tissues and blood, from a cohort of 69 CRC patients. We found several signs of immune suppression in tumours compared to adjacent non-malignant tissues, including T cells more often expressing the immune checkpoint molecules programmed cell death protein (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). We further analysed immune cell infiltration in molecular subgroups of CRC. MSI tumours were indeed found to be associated with increased immune infiltration, including increased fractions of PD-1+ T cells. No correlation was, however, found between MSI and the fraction of CTLA-4+ T cells. Interestingly, within the group of patients with microsatellite stable (MSS) tumours, some also presented with increased immune infiltration, including comparably high portions of PD-1+ T cells, but also CTLA-4+ T cells. Furthermore, no correlation was found between PD-1+ and CTLA-4+ T cells, suggesting that different tumours may, to some extent, be regulated by different immune checkpoints. We further evaluated the distribution of immune activity profiles in the consensus molecular subtypes of CRC. In conclusion, our findings suggest that different immune checkpoint inhibitors may be beneficial for selected CRC patients irrespective of MSI status. Improved predictive tools are required to identify these patients.
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39.
  • Li, Xingru, et al. (författare)
  • A modified protein marker panel to identify four consensus molecular subtypes in colorectal cancer using immunohistochemistry
  • 2021
  • Ingår i: Pathology, Research and Practice. - : Elsevier. - 0344-0338 .- 1618-0631. ; 220
  • Tidskriftsartikel (refereegranskat)abstract
    • Colorectal cancer (CRC) is a heterogeneous disease with different genetic and molecular backgrounds, leading to a diverse patient prognosis and treatment response. Four consensus molecular subtypes (CMS 1–4) have recently been proposed based on transcriptome profiling. A clinically practical immunohistochemistry (IHC) based CMS classifier consisting of the four markers FRMD6, ZEB1, HTR2B, and CDX2 was then demonstrated. However, the IHC-CMS classifier did not distinguish between CMS2 and CMS3 tumours. In this study, we have applied the proposed transcriptome based and IHC-based CMS classifiers in a CRC cohort of 65 patients and found a concordance of 77.5 %. Further, we modified the IHC-CMS classifier by analysing the differentially expressed genes between CMS2 and CMS3 tumours using RNA-sequencing data from the TCGA dataset. The result showed that WNT signalling was among the most upregulated pathways in CMS2 tumours, and the expression level of CTNNB1 (encoding β-catenin), a WNT pathway hallmark, was significantly upregulated (P = 1.15 × 10−6). We therefore introduced nuclear β-catenin staining to the IHC-CMS classifier. Using the modified classifier in our cohort, we found a 71.4 % concordance between the IHC and RNA-sequencing based CMS classifiers. Moreover, β-catenin staining could classify 16 out of the 19 CMS2/3 tumours into CMS2 or CMS3, thereby showing an 84.2 % concordance with the RNA-sequencing-based classifier. In conclusion, we evaluated CMS classifiers based on transcriptome and IHC analysis. We present a modified IHC panel that categorizes CRC tumours into the four CMS groups. To our knowledge, this is the first study using IHC to identify all four CMS groups.
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40.
  • Li, Xingru, et al. (författare)
  • Ex Vivo Organoid Cultures Reveal the Importance of the Tumor Microenvironment for Maintenance of Colorectal Cancer Stem Cells
  • 2020
  • Ingår i: Cancers. - : MDPI. - 2072-6694. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Colorectal cancer (CRC) is a heterogeneous disease, with varying clinical presentations and patient prognosis. Different molecular subgroups of CRC should be treated differently and therefore, must be better characterized. Organoid culture has recently been suggested as a good model to reflect the heterogeneous nature of CRC. However, organoid cultures cannot be established from all CRC tumors. The study examines which CRC tumors are more likely to generate organoids and thus benefit from ex vivo organoid drug testing. Long-term organoid cultures from 22 out of 40 CRC tumor specimens were established. It was found that organoid cultures were more difficult to establish from tumors characterized as microsatellite instable (MSI), BRAF-mutated, poorly differentiated and/or of a mucinous type. This suggests that patients with such tumors are less likely to benefit from ex vivo organoid drug testing, but it may also suggest biological difference in tumor growth. RNA sequencing analysis of tumor sections revealed that the in vivo maintenance of these non-organoid-forming tumors depends on factors related to inflammation and pathogen exposure. Furthermore, using TCGA data we could show a trend towards a worse prognosis for patients with organoid-forming tumors, suggesting also clinical differences. Results suggest that organoids are more difficult to establish from tumors characterized as MSI, BRAF-mutated, poorly differentiated and/or of a mucinous type. We further suggest that the maintenance of cell growth of these tumors in vivo may be promoted by immune-related factors and other stromal components within the tumor microenvironment.
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41.
  • Liedberg, Fredrik, et al. (författare)
  • Anorectal dysfunction after radical cystectomy for bladder cancer
  • 2022
  • Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 56:2, s. 155-161
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To prospectively assess anorectal dysfunction using patient-reported outcomes using validated questionnaires, manovolumetry and endoanal ultrasound before and 12 months after RC. Patients and methods: From 2014 to 2019, we prospectively included 44 patients scheduled for RC. Preoperatively and 12 months after surgery, 41 patients filled in a low anterior resection syndrome score (LARS-score) to assess fecal incontinence, increased frequency, urgency and emptying difficulties and a St Mark’s score to assess fecal incontinence in conjunction with manovolumetry and endoanal ultrasound examinations. Pre- and postoperative patient-reported anorectal dysfunction were assessed by LARS-score and St Marks’s score. At the same time-points, anorectal function was evaluated by measuring mean anal resting and maximal squeeze pressures, volumes and pressures at first desire, urgency to defecate and maximum toleration during manovolumetry. Wilcoxon's signed rank test was used to compare pre- and postoperative outcomes by questionnaires. Results: Postoperatively 6/41 (15%) patients reported flatus incontinence assessed by the LARS-questionnaire, and correspondingly the St Mark’s score increased postoperatively. The median anal resting pressure decreased from 57 mmHg preoperatively to 46 mmHg after RC, but without any postoperative anatomic defects detected by endoanal ultrasound. Volumes and pressures at first desire, urgency to defecate and maximum toleration during manovolumetry all increased after RC, indicating decreased postoperative rectal sensation, as rectal compliance was unaltered. Conclusions: Postoperative flatus incontinence is reported by one out of seven patients after RC, which corresponds to decreased anal resting pressures. The finding of decreased rectal sensation might also contribute to patient-reported symptoms and anorectal dysfunction after RC.
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42.
  • Liedberg, Fredrik, et al. (författare)
  • Fast-track access to urologic care for patients with macroscopic haematuria is efficient and cost-effective : results from a prospective intervention study
  • 2016
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 115, s. 770-775
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:The delay between onset of macroscopic haematuria and diagnosis of bladder cancer is often long.Methods:We evaluated timely diagnosis and health-care costs for patients with macroscopic haematuria given fast-track access to diagnostics. During a 15-month period, a telephone hotline for fast-track diagnostics was provided in nine Swedish municipalities for patients aged ⩾50 years with macroscopic haematuria. The control group comprised 101 patients diagnosed with bladder cancer in the same catchment area with macroscopic haematuria who underwent regular diagnostic process.Results:In all 275 patients who called ‘the Red Phone’ hotline were investigated, and 47 of them (17%) were diagnosed with cancer and 36 of those had bladder cancer. Median time from patient-reported haematuria to diagnosis was 29 (interquartile range (IQR) 14−104) days and 50 (IQR 27−165) days in the intervention and the control group, respectively (P=0.03). The median health-care costs were lower in the intervention group (655 (IQR 655−655) EUR) than in the control group (767 (IQR 490−1096) EUR) (P=0.002).Conclusions:Direct access to urologic expertise and fast-track diagnostics is motivated for patients with macroscopic haematuria to reduce diagnostic intervals and lower health-care expenditures.British Journal of Cancer advance online publication, 25 August 2016; doi:10.1038/bjc.2016.265 www.bjcancer.com.
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43.
  • Ling, Agnes, 1976-, et al. (författare)
  • TAP1 down-regulation elicits immune escape and poor prognosis in colorectal cancer
  • 2017
  • Ingår i: Oncoimmunology. - 2162-4011 .- 2162-402X. ; 6:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The anti-tumor immune response has been shown to be of great prognostic importance in colorectal cancer (CRC) and so has the tumors ability for immune evasion. Our aim of this study was to investigate tumor factors that influence immunity. We used a gene expression array to search for potential mechanisms of tumor immune escape. One candidate gene identified was TAP1, involved in antigen presentation by MHC class I. TAP1 protein expression was evaluated by immunohistochemistry in 436 CRC patients of the Colorectal Cancer in Umeå Study cohort. We found a significant association between a downregulated expression of TAP1 and low infiltration of various subtypes of lymphocytes as well as macrophages. A downregulated expression of TAP1 was further found to be independent of molecular characteristics, suggesting TAP1 down-regulation to reach beyond the well described highly immunogenic MSI CRCs. A low expression of TAP1 was also significantly associated with poor prognosis in patients with CRC, a result that stayed significant in tumor front of early stage tumors (stage I-II) through multivariable analyses. Furthermore, we found that TAP1 expression was inversely correlated with methylation at sites in close proximity to the promoter region. In summary, our results show down-regulation of TAP1 to be a general mechanism of tumor immune escape in CRC and a poor prognostic factor in stage I-II CRC patients. We also suggest that methylation of the TAP1 gene may be a putative mechanism for TAP1 downregulation.
  •  
44.
  • Lorenzzi Löfgren de Melo, Alexandra, et al. (författare)
  • Single-molecule array assay reveals the prognostic impact of plasma LRIG1 in ovarian carcinoma
  • 2022
  • Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 61:11, s. 1425-1433
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Ovarian carcinoma is the eighth most common cause of cancer death in women worldwide. The disease is predominantly diagnosed at a late stage. This contributes to high recurrence rates, eventually leading to the development of treatment-resistant disease. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is a transmembrane protein that functions as a tumor suppressor and regulator of growth factor signaling. LRIG1 levels have not been investigated in human plasma previously.Materials and methods: A quantitative LRIG1-specific single molecule array assay was developed and validated. LRIG1 levels were quantified in plasma samples from 486 patients with suspicious ovarian masses.Results: Among women with ovarian carcinoma, LRIG1 levels were significantly elevated compared to women with benign or borderline type tumors. High LRIG1 plasma levels were associated with worse overall survival and shorter disease-free survival both in the group of all malignant cases and among the stage 3 cases only. LRIG1 was an independent prognostic factor in patients with stage 3 ovarian carcinoma.Conclusion: LRIG1 plasma levels were elevated in patients with ovarian carcinoma, and high levels were associated with poor prognosis, suggesting that LRIG1 might be an etiologic factor and a potentially useful biomarker in ovarian carcinoma.
  •  
45.
  • Lundberg, Ida, et al. (författare)
  • MicroRNA expression in KRAS- and BRAF-mutated colorectal cancers
  • 2018
  • Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 38:2, s. 677-683
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aim: KRAS and BRAF are two genes commonly mutated in colorectal cancer (CRC). Even though BRAF is a downstream target of KRAS in the MAPK signalling pathway, KRAS- and BRAF-mutated CRCs are found to display several different clinical and histopathological features. We investigated whether a differential expression of microRNAs (miRNAs) could explain the clinicopathological differences seen between KRAS-and BRAF-mutated CRCs.Materials and Methods: Using a PCR array, we analyzed the expression of 84 different miRNAs in CRC cell lines wild-type in KRAS and BRAF, or mutated in KRAS or BRAF.Results: Ten miRNAs were selected for further analyses in tumor tissue specimens (let-7a, let-7i, miR-10a, miR-10b, miR-31, miR-100, miR-181a, miR-181b, miR-372, and miR-373). BRAF-mutated tumors were found to express significantly higher levels of miR-31 as well as significantly lower levels of miR-373, compared to wild-type tumors.Conclusion: Our results suggest that KRAS and BRAF-mutated CRCs may have different miRNA signatures compared to CRC tumors wild-type in KRAS and BRAF. However, no difference in expression levels between KRAS-and BRAF-mutated tumors was evident for the miRNAs analyzed in this study.
  •  
46.
  • Lundberg, Ida V, et al. (författare)
  • SOX2 expression is regulated by BRAF and contributes to poor patient prognosis in colorectal cancer
  • 2014
  • Ingår i: PLOS ONE. - : Public library of science. - 1932-6203. ; 9:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Sporadic colorectal cancer (CRC) is a common malignancy and also one of the main causes of cancer deaths worldwide. Aberrant expression of the transcription factor SOX2 has recently been observed in several cancer types, but its role in CRC has not been fully elucidated. Here we studied the expression of SOX2 in 441 CRC patients by immunohistochemistry and related the expression to clinicopathological and molecular variables and patient prognosis. SOX2 was expressed in 11% of the tumors and was significantly associated to BRAF(V600E) mutation, but not to KRAS mutations (codon 12 and 13). SOX2 positivity was correlated to poor patient survival, especially in BRAF(V600E) mutated cases. In vitro studies showed that cells expressing the constitutively active BRAF(V600E) had increased SOX2 expression, a finding not found in cells expressing KRAS(G12V). Furthermore, blocking downstream BRAF signalling using a MEK-inhibitor resulted in a decreased expression of SOX2. Since SOX2 overexpression has been correlated to increased migration and invasion, we investigated the SOX2 expression in human CRC liver metastasis and found that a SOX2 positive primary CRC also had SOX2 expression in corresponding liver metastases. Finally we found that cells overexpressing SOX2 in vitro showed enhanced expression of FGFR1, which has been reported to correlate with liver metastasis in CRC. Our novel findings suggest that SOX2 expression is partly regulated by BRAF signalling, and an increased SOX2 expression may promote CRC metastasis and mediate a poor patient prognosis.
  •  
47.
  • Lundholm, Marie, 1974-, et al. (författare)
  • Defective induction of CTLA-4 in the NOD mouse is controlled by the NOD allele of Idd3/IL-2 and a novel locus (Ctex) telomeric on chromosome 1
  • 2006
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 55:2, s. 538-544
  • Tidskriftsartikel (refereegranskat)abstract
    • Cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4), or CD152, is a negative regulator of T-cell activation and has been shown to be associated with autoimmune diseases. Previous work has demonstrated a defect in the expression of this molecule in nonobese diabetic (NOD) mice upon anti-CD3 stimulation in vitro. Using a genetic approach we here demonstrate that a novel locus (Ctex) telomeric on chromosome 1 together with the Idd3 (Il-2) gene confers optimal CTLA-4 expression upon CD3 activation of T-cells. Based on these data, we provide a model for how gene interaction between Idd3 (IL-2), Ctex, and Idd5.1 (Ctla-4) could confer susceptibility to autoimmune diabetes in the NOD mouse. Additionally, we showed that the Ctex and the Idd3 regions do not influence inducible T-cell costimulator (ICOS) protein expression in NOD mice. Instead, as previously shown, higher ICOS levels in NOD mice appear to be controlled by gene(s) in the Idd5.1 region, possibly a polymorphism in the Icos gene itself.
  •  
48.
  •  
49.
  • Lundholm, Marie, et al. (författare)
  • Variation in the Cd3 zeta (Cd247) gene correlates with altered T cell activation and is associated with autoimmune diabetes.
  • 2010
  • Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 184:10, s. 5537-5544
  • Tidskriftsartikel (refereegranskat)abstract
    • Tuning of TCR-mediated activation was demonstrated to be critical for lineage fate in T cell development, as well as in the control of autoimmunity. In this study, we identify a novel diabetes susceptibility gene, Idd28, in the NOD mouse and provide evidence that Cd3zeta (Cd247) constitutes a prime candidate gene for this locus. Moreover, we show that the allele of the Cd3zeta gene expressed in NOD and DBA/2 mouse strains confers lower levels of T cell activation compared with the allele expressed by C57BL/6 (B6), BALB/c, and C3H/HeJ mice. These results support a model in which the development of autoimmune diabetes is dependent on a TCR signal mediated by a less-efficient NOD allele of the Cd3zeta gene.
  •  
50.
  • Löfgren, Anna, et al. (författare)
  • Hospital costs and health-related quality of life from complications after esophagectomy
  • 2021
  • Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983. ; S0748-7983:20, s. 30804-0
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Approximately 50% of all patients undergoing esophagectomy experience complications. This paper estimates the costs due to complications after esophagectomy in a Swedish context. Material and methods: The Swedish National Register for Esophageal and Gastric Cancer (NREV) and the Healthcare Consumption Register in Region Skåne (RSVD) were crossmatched for patients undergoing esophagectomy between 2010 and 2015 in Region Skåne, Sweden (n = 132). Multivariable linear regression analysis was performed on the logarithm of total healthcare cost. HRQoL was presented descriptively. Results: The mean total healthcare costs were 335,016 SEK (€33,502) for the group with no complications and 438,320 SEK (€43,832) and 808,461 SEK (€80,846) for minor and major complications (p < 0.001), respectively. Pneumonia (p < 0.001), laryngeal nerve paresis (p = 0.002) and other complications (p < 0.001) showed significant associations with increased healthcare cost. No significant difference was found in QALY-weights between the complication grades. Patients that underwent esophagectomy reported poorer HRQoL than the scores valued by the general background population. Conclusion: Complications following esophagectomy incrementally increase the healthcare costs, where more severe complications led to higher healthcare costs. The severity of complications did not affect the mean QALY-weights.
  •  
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