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31.
  • Jiang, Huiqi, 1981- (författare)
  • NT-proBNP as a marker of postoperative heart failure in adult cardiac surgery
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Postoperative heart failure (PHF) remains the major cause of mortality after cardiac surgery. Unfortunately, generally accepted diagnostic criteria for PHF are lacking. This may explain why the evidence for the efficacy and safety of current treatment of PHF with inotropes is insufficient. In cardiology practice N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an established biomarker for heart failure. However, the association between NT-proBNP and PHF after cardiac surgery needs further clarification. Glutamate is a key intermediate in myocardial metabolism, which may improve myocardial tolerance to ischemia and facilitate post-ischemic recovery. Glutamate was associated with a reduced risk of developing severe PHF in high-risk patients undergoing coronary artery bypass surgery (CABG). The aim of this thesis was to study the role of NT-proBNP for prediction and assessment of PHF in cardiac surgery (Paper I-III) and the impact of intravenous glutamate infusion on postoperative NTproBNP after CABG (Paper IV).Paper I: We retrospectively studied the role of underlying heart disease for preoperative NT-proBNP in patients admitted for first time CABG (n=2226), aortic valve surgery (AVR) for aortic stenosis (AS) (n=406) and mitral valve surgery for mitral valve regurgitation (MR) (n=346) by adjusting for non-cardiac confounders (age, gender, obesity and renal function). The level of NT-proBNP in AS or MR was 1.67 (p<0.0001) and 1.41 times (p<0.0001) higher respectively than in coronary artery disease (CAD) after adjusting for confounders. Preoperative NT-proBNP was predictive of severe PHF in CAD and MR patients but less so in AS patients. Preoperative NT-proBNP emerged as an independent risk factor for severe PHF and postoperative mortality in CAD patients.Paper II-III: We prospectively studied the association between postoperative NT-proBNP and PHF in two cohorts, patients undergoing AVR for AS (n=203) and patients undergoing isolated CABG for acute coronary syndrome (ACS) from the GLUTAMICS-trial (n=382). NT-proBNP was measured preoperatively, on the first (POD1) and third postoperative morning (POD3). An end-points committee blinded to NT-proBNP used prespecified criteria to diagnose PHF and its severity. After AVR for AS only NT-proBNP level on POD1 provided good discrimination of PHF. PHF with NT-proBNP POD1 ≥ 5290 ng•L-1 emerged as an independent risk factor for long-term mortality (Paper II). After isolated CABG for ACS both absolute postoperative levels on POD1 and POD3 and postoperative increases of NT-proBNP were associated with PHF and the levels reflected the severity of PHF (Paper III).Paper IV: We prospectively studied the impact of intravenous glutamate infusion on postoperative NT-proBNP in a randomized double-blind study on patients undergoing CABG for ACS from the GLUTAMICS-trial (n=399). Patients were randomly allocated to intravenous infusion of L-glutamate (n=200) or saline (n=199). No effect of glutamate on postoperative NT-proBNP levels was detected in the whole cohort. According to post-hoc analysis glutamate was associated with less increase of NT-proBNP from preoperative level to POD3 and significantly lower absolute levels on POD3 among high risk patients with EuroSCORE II ≥4.15 (upper quartile).Conclusion: Patients with AS or MR have higher preoperative NT-proBNP than CAD patients after adjusting for confounders. The predictive value of NT-proBNP with regard to severe PHF and postoperative mortality was confirmed in CAD patients. Postoperative NTproBNP may prove a useful tool for assessment of PHF after AVR for AS and isolated CABG. NT-proBNP POD1 identifies patients with PHF at risk of a poor long-term survival after AVR for AS. Intravenous infusion of glutamate may prevent or mitigate PHF in highrisk patients undergoing CABG but these results need to be confirmed.
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32.
  • Jonsson, Åsa, 1969- (författare)
  • How to create and analyze a Heart Failure Registry with emphasis on Anemia and Quality of Life
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background and aimsHeart failure (HF) is a major cause of serious morbidity and death in the population and one of the leading medical causes of hospitalization among people older than 60 years. The aim of this thesis was to describe how to create and how to analyze a Heart Failure Registry with emphasis on Anemia and Quality of Life. (Paper I) We described the creation of the Swedish Heart Failure Registry (SwedeHF) as an instrument, which may help to optimize the handling of HF patients and show how the registry can be used to improve the management of patients with HF. (Paper II) In order to show how to analyze a HF registry we investigated the prevalence of anemia, its predictors, and its association with mortality and morbidity in a large cohort of unselected patients with HFrEF included in the SwedeHF, and to explore if there are subgroups of HF patients identifying high--‐risk patients in need of treatment. (Paper III) In order to show another way of analyzing a HF registry we assessed the prevalence of, associations with, and prognostic impact of anemia in patients with HFmrEF and HFpEF. (Paper IV) Finally we examined the usefulness of EQ--‐ 5D as a measure of patient--‐reported outcomes among HF patients using different analytical models and data from the SwedeHF, and comparing results about HRQoL for patients with HFpEF and HFrEF.Methods An observational study based on the SwedeHF database, consisting of about 70 variables, was undertaken to describe how a registry is created and can be used (Paper I). One comorbidity (anemia) was applied to different types of HF patients, HFrEF (EF <40%) (II) and HFmrEF (EF 40--‐49% ) or HFpEF (> 50%) (III) analyzing the data with different statistical methods. The usefulness of EQ--‐5D as measure of patient--‐ reported outcomes was studied and the results about HRQoL were compared for patients with HFpEF and HFrEF (IV).ResultsIn the first paper (Paper I) we showed how to create a HF registry and presented some characteristics of the patients included, however not adjusted since this was not the purpose of the study. In the second paper (Paper II) we studied anemia in patients with HFrEF and found that the prevalence of anemia in HFrEF were 34 % and the most important independent predictors were higher age, male gender and renal dysfunction. One--‐year survival was 75 % with anemia vs. 81 % without (p<0,001). In the matched cohort after propensity score the hazard ratio associated with anemia was for all--‐cause death 1.34. Anemia was associated with greater risk with lower age, male gender, EF 30--‐39%, and NYHA--‐class I--‐II. In the third paper (Paper III) we studied anemia in other types of HF patients and found that the prevalence in the overall cohort in patients with EF > 40% was 42 %, in HFmrEF 38 % and in HFpEF (45%). Independent associations with anemia were HFpEF, male sex, higher age, worse New York Heart Association class and renal function, systolic blood pressure <100 mmHg, heart rate ≥70 bpm, diabetes, and absence of atrial fibrillation. One--‐year survival with vs. without anemia was 74% vs. 89% in HFmrEF and 71% vs. 84% in HFpEF (p<0.001 for all). Thus very similar results in paper II and III but in different types of HF patients. In the fourth paper (Paper IV) we studied the usefulness of EQ--‐5D in two groups of patients with HF (HFpEF and HFrEF)) and found that the mean EQ--‐5D index showed small reductions in both groups at follow--‐up. The patients in the HFpEF group reported worsening in all five dimensions, while those in the HFrEF group reported worsening in only three. The Paretian classification showed that 24% of the patients in the HFpEF group and 34% of those in the HFrEF group reported overall improvement while 43% and 39% reported overall worsening. Multiple logistic regressions showed that treatment in a cardiology clinic affected outcome in the HFrEF group but not in the HFpEF group (Paper IV).Conclusions The SwedeHF is a valuable tool for improving the management of patients with HF, since it enables participating centers to focus on their own potential for improving diagnoses and medical treatment, through the online reports (Paper I). Anemia is associated with higher age, male gender and renal dysfunction and increased risk of mortality and morbidity (II, III). The influence of anemia on mortality was significantly greater in younger patients in men and in those with more stable HF (Paper II, III). The usefulness of EQ--‐5D is dependent on the analytical method used. While the index showed minor differences between groups, analyses of specific dimensions showed different patterns of change in the two groups of patients (HFpEF and HFrEF). The Paretian classification identified subgroups that improved or worsened, and can therefore help to identify needs for improvement in health services (Paper IV).
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33.
  • Alevronta, Eleftheria, et al. (författare)
  • Dose-response relationships of intestinal organs and excessive mucus discharge after gynaecological radiotherapy
  • 2021
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 16:4 April
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The study aims to determine possible dose-volume response relationships between the rectum, sigmoid colon and small intestine and the ‘excessive mucus discharge’ syndrome after pelvic radiotherapy for gynaecological cancer. Methods and materials From a larger cohort, 98 gynaecological cancer survivors were included in this study. These survivors, who were followed for 2 to 14 years, received external beam radiation therapy but not brachytherapy and not did not have stoma. Thirteen of the 98 developed excessive mucus discharge syndrome. Three self-assessed symptoms were weighted together to produce a score interpreted as ‘excessive mucus discharge’ syndrome based on the factor loadings from factor analysis. The dose-volume histograms (DVHs) for rectum, sigmoid colon, small intestine for each survivor were exported from the treatment planning systems. The dose-volume response relationships for excessive mucus discharge and each organ at risk were estimated by fitting the data to the Probit, RS, LKB and gEUD models. Results The small intestine was found to have steep dose-response curves, having estimated dose-response parameters: γ : 1.28, 1.23, 1.32, D : 61.6, 63.1, 60.2 for Probit, RS and LKB respectively. The sigmoid colon (AUC: 0.68) and the small intestine (AUC: 0.65) had the highest AUC values. For the small intestine, the DVHs for survivors with and without excessive mucus discharge were well separated for low to intermediate doses; this was not true for the sigmoid colon. Based on all results, we interpret the results for the small intestine to reflect a relevant link. Conclusion An association was found between the mean dose to the small intestine and the occurrence of ‘excessive mucus discharge’. When trying to reduce and even eliminate the incidence of ‘excessive mucus discharge’, it would be useful and important to separately delineate the small intestine and implement the dose-response estimations reported in the study.
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34.
  • Meijnikman, A. S., et al. (författare)
  • Microbiome-derived ethanol in nonalcoholic fatty liver disease
  • 2022
  • Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28:10, s. 2100-2106
  • Tidskriftsartikel (refereegranskat)abstract
    • A new study examines microbiome-generated ethanol in individuals with and without nonalcoholic fatty liver disease (NAFLD), concluding that microbial ethanol might contribute to pathogenesis in some patients with NAFLD. To test the hypothesis that the gut microbiota of individuals with nonalcoholic fatty liver disease (NAFLD) produce enough ethanol to be a driving force in the development and progression of this complex disease, we performed one prospective clinical study and one intervention study. Ethanol was measured while fasting and 120 min after a mixed meal test (MMT) in 146 individuals. In a subset of 37 individuals and in an external validation cohort, ethanol was measured in portal vein blood. In an intervention study, ten individuals with NAFLD and ten overweight but otherwise healthy controls were infused with a selective alcohol dehydrogenase (ADH) inhibitor before an MMT. When compared to fasted peripheral blood, median portal vein ethanol concentrations were 187 (interquartile range (IQR), 17-516) times higher and increased with disease progression from 2.1 mM in individuals without steatosis to 8.0 mM in NAFL 21.0 mM in nonalcoholic steatohepatitis. Inhibition of ADH induced a 15-fold (IQR,1.6- to 20-fold) increase in peripheral blood ethanol concentrations in individuals with NAFLD, although this effect was abolished after antibiotic treatment. Specifically, Lactobacillaceae correlated with postprandial peripheral ethanol concentrations (Spearman's rho, 0.42; P < 10(-5)) in the prospective study. Our data show that the first-pass effect obscures the levels of endogenous ethanol production, suggesting that microbial ethanol could be considered in the pathogenesis of this highly prevalent liver disease.
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35.
  • Papakokkinou, Eleni, et al. (författare)
  • Prevalence of Nelson's syndrome after bilateral adrenalectomy in patients with cushing's disease: a systematic review and meta-analysis
  • 2021
  • Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403.
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Bilateral adrenalectomy (BA) still plays an important role in the management of Cushing's disease (CD). Nelson's syndrome (NS) is a severe complication of BA, but conflicting data on its prevalence and predicting factors have been reported. The aim of this study was to determine the prevalence of NS, and identify factors associated with its development. Data sources Systematic literature search in four databases. Study Selection Observational studies reporting the prevalence of NS after BA in adult patients with CD. Data extraction Data extraction and risk of bias assessment were performed by three independent investigators. Data synthesis Thirty-six studies, with a total of 1316 CD patients treated with BA, were included for the primary outcome. Pooled prevalence of NS was 26% (95% CI 22-31%), with moderate to high heterogeneity (I-2 67%, P < 0.01). The time from BA to NS varied from 2 months to 39 years. The prevalence of NS in the most recently published studies, where magnet resonance imaging was used, was 38% (95% CI 27-50%). The prevalence of treatment for NS was 21% (95% CI 18-26%). Relative risk for NS was not significantly affected by prior pituitary radiotherapy [0.9 (95% CI 0.5-1.6)] or pituitary surgery [0.6 (95% CI 0.4-1.0)]. Conclusions Every fourth patient with CD treated with BA develops NS, and every fifth patient requires pituitary-specific treatment. The risk of NS may persist for up to four decades after BA. Life-long follow-up is essential for early detection and adequate treatment of NS.
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36.
  • Steineck, Gunnar, 1952, et al. (författare)
  • Contouring pudendal nerves.
  • 2018
  • Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 57:4, s. 438-439
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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37.
  • Robertson, Josefina, et al. (författare)
  • Serum neopterin levels in relation to mild and severe COVID-19
  • 2020
  • Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, is rapidly spreading worldwide. There is limited information about prognostic markers that could help clinicians to identify COVID-19 patients with a poor prognosis. Serum levels of the immune activation marker neopterin has shown to be of prognostic value in patients with SARS. The aim of this study was to investigate whether serum neopterin is associated with the severity of COVID-19. Methods: We included 34 patients with confirmed COVID-19 between March 3 and March 30, 2020. Fifteen patients had mild disease and did not require hospitalization, whereas 19 patients developed severe COVID-19 requiring intensive care. Concentrations of serum neopterin, tryptophan, and kynurenine were measured at and repeatedly after inclusion. Results: We found a more than two-fold higher mean concentration of neopterin in severely ill patients (mean value 42.0 nmol/L (SD 18.2)) compared to patients with mild symptoms (16.9 nmol/L (SD 11.0)). All of the severe cases had elevated neopterin concentrations (> 9.1 nmol/L) at the initial sampling with values ranging from 17.2 to 86.7 nmol/L. In comparison, 10 of 15 patients with mild disease had neopterin levels above 9.1 nmol/L, with concentrations in the range from 4.9 to 31.6 nmol/L. Neopterin levels gradually decreased during the course of COVID-19, but severe cases maintained elevated levels for a longer period. Moreover, lower levels of tryptophan and higher levels of kynurenine, indicating an increased tryptophan catabolism, were seen in the group with severe cases. Conclusions: In conclusion, we found that serum neopterin levels are associated with the severity of COVID-19. Our findings suggest that neopterin could be used as a prognostic marker, but further studies are needed to elucidate how it can be used in the clinic.
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38.
  • Andersson, John, 1978, et al. (författare)
  • Developing a multivariable prediction model of global health-related quality of life in patients treated for rectal cancer : a prospective study in five countries
  • 2024
  • Ingår i: International Journal of Colorectal Disease. - : Springer Nature. - 0179-1958 .- 1432-1262. ; 39
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Rectal cancer and its treatment have a negative impact on health-related quality of life (HRQoL). If risk factors for sustained low HRQoL could be identified early, ideally before the start of treatment, individualised interventions could be identified and implemented to maintain or improve HRQoL. The study aimed to develop a multivariable prediction model for global HRQoL 12 months after rectal cancer treatment.Methods Within COLOR II, a randomised, multicentre, international trial of laparoscopic and open surgery for rectal cancer, a sub-study on HRQoL included 385 patients in 12 hospitals and five countries. The HRQoL study was optional for hospitals in the COLOR II trial. EORTC QLQ-C30 and EORTC QLQ-CR38 were analysed preoperatively and at 1 and 12 months postoperatively. In exploratory analyses, correlations between age, sex, fatigue, pain, ASA classification, complications, and symptoms after surgery to HRQoL were studied. Bivariate initial analyses were followed by multivariate regression models.Results Patient characteristics and clinical factors explained 4–10% of the variation in global HRQoL. The patient-reported outcomes from EORTC QLQ-C30 explained 55–65% of the variation in global HRQoL. The predominant predictors were fatigue and pain, which significantly impacted global HRQoL at all time points measured.Conclusion We found that fatigue and pain were two significant factors associated with posttreatment global HRQoL in patients treated for rectal cancer T1-T3 Nx. Interventions to reduce fatigue and pain could enhance global HRQoL after rectal cancer treatment.
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39.
  • Forssell-Aronsson, Eva, 1961, et al. (författare)
  • Indium-111 activity concentration in tissue samples after intravenous injection of indium-111-DTPA-D-Phe-1-octreotide.
  • 1995
  • Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 36:1, s. 7-12
  • Tidskriftsartikel (refereegranskat)abstract
    • Indium-111 activity concentrations in human tumor and normal tissue samples were determined at 24, 48 and 120 hr after i.v. injection of 111In-DTPA-D-Phe-1-octreotide. Fourteen patients were included in the study. Seven patients had medullary thyroid carcinoma, four had midgut carcinoid tumors, two had endocrine pancreatic tumors and one had chronic pancreatitis.
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40.
  • Glimelius, Bengt, et al. (författare)
  • Persistent prevention of oxaliplatin-induced peripheral neuropathy using calmangafodipir (PledOx®) : a placebo-controlled randomised phase II study (PLIANT)
  • 2018
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 57:3, s. 393-402
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Oxaliplatin causes disabling acute and chronic peripheral neuropathy. We explored the preventive effects of calmangafodipir, mimicking the mitochondrial enzyme manganese superoxide dismutase, thereby protecting cells from oxidative stress, in a placebo-controlled, double-blinded randomised phase II study (ClinicalTrials.gov.NCT01619423) in patients with metastatic colorectal cancer (mCRC).Patient and methods: mCRC patients treated with modified FOLFOX-6 (folinic acid 200 mg/m2, 5-fluorouracil bolus 400 mg/m2, oxaliplatin 85 mg/m2 and 5-fluorouracil 2400 mg/m2 continuous infusion for 46 h) every fortnight for 8 cycles in first or second line were eligible. Calmangafodipir was given in a phase I dose-finding and in a phase II placebo-controlled study, as a 5-min infusion 10 min prior to oxaliplatin. Neurotoxicity was evaluated by the physician using the Oxaliplatin Sanofi Specific Scale and by the patient using the cold allodynia test and the Leonard scale.Results: Eleven patients were included in phase I without any detectable toxicity to calmangafodipir. In the phase II study, 173 patients were randomised to placebo (n = 60), calmangafodipir 2 µmol/kg (n = 57) and calmangafodipir 5 µmol/kg (n = 45, initially 10 µmol/kg, n = 11). Calmangafodipir-treated patients (all three doses pooled) had less physician graded neurotoxicity (odds ratio (90% confidence interval one-sided upper level) 0.62(1.15), p = .16), significantly less problems with cold allodynia (mean 1.6 versus 2.3, p < .05) and significantly fewer sensory symptoms in the Leonard scale (cycle 1–8 mean 1.9 versus 3.0, p < .05 and during follow-up after 3 and 6 months, mean 3.5 versus 7.3, p < .01). Response rate, progression-free and overall survival did not differ among groups.Conclusions: Calmangafodipir at a dose of 5 µmol/kg appears to prevent the development of oxaliplatin-induced acute and delayed CIPN without apparent influence on tumour outcomes.
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