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1.
  • Lewerin, C., et al. (författare)
  • Low holotranscobalamin and cobalamins predict incident fractures in elderly men: the MrOS Sweden.
  • 2014
  • Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - 1433-2965. ; 25:1, s. 131-140
  • Tidskriftsartikel (refereegranskat)abstract
    • SummaryIn a population-based study on cobalamin status and incident fractures in elderly men (n  = 790) with an average follow-up of 5.9 years, we found that low levels of metabolically active and total cobalamins predict incident fractures, independently of body mass index (BMI), bone mineral density (BMD), plasma total homocysteine (tHcy), and cystatin C.IntroductionCobalamin deficiency in elderlies may affect bone metabolism. This study aims to determine whether serum cobalamins or holotranscobalamin (holoTC; the metabolic active cobalamin) predict incident fractures in old men.MethodsMen participating in the Gothenburg part of the population-based Osteoporotic Fractures in Men (MrOS) Sweden cohort and without ongoing vitamin B medication were included in the present study (n = 790; age range, 70–81 years).ResultsDuring an average follow-up of 5.9 years, 110 men sustained X-ray-verified fractures including 45 men with clinical vertebral fractures. The risk of fracture (adjusted for age, smoking, BMI, BMD, falls, prevalent fracture, tHcy, cystatin C, 25-OH-vitamin D, intake of calcium, and physical activity (fully adjusted)), increased per each standard deviation decrease in cobalamins (hazard ratio (HR), 1.38; 95 % confidence intervals (CI), 1.11–1.72) and holoTC (HR, 1.26; 95 % CI, 1.03–1.54), respectively. Men in the lowest quartile of cobalamins and holoTC (fully adjusted) had an increased risk of all fracture (cobalamins, HR = 1.67 (95 % CI, 1.06–2.62); holoTC, HR = 1.74 (95 % CI, 1.12–2.69)) compared with quartiles 2–4. No associations between folate or tHcy and incident fractures were seen.ConclusionsWe present novel data showing that low levels of holoTC and cobalamins predicting incident fracture in elderly men. This association remained after adjustment for BMI, BMD, tHcy, and cystatin C. However, any causal relationship between low cobalamin status and fractures should be explored in a prospective treatment study.
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2.
  • Nordberg, Marika, et al. (författare)
  • Aetiology of Tick-Borne Infections in an Adult Swedish Population—Are Co-Infections with Multiple Agents Common?
  • 2014
  • Ingår i: Open Journal of Clinical Diagnostics. - Scientific Research Publishing. - 2162-5816. ; 4:1, s. 31-40
  • Tidskriftsartikel (refereegranskat)abstract
    • In Scandinavia, tick-borne infections affecting humans include Lyme borreliosis (LB), tick-borne encephalitis (TBE) and human granulocytic anaplasmosis (HGA). Each of these infections can present with unspecific symptoms. In this prospective clinical study, we recruited patients based on two independent inclusion criteria; 1) patients with unspecific symptoms, i.e. fever (≥38.0℃) or a history of feverishness and/or any combination of headache, myalgia or arthralgia and 2) patients with erythema migrans (EM), following an observed tick bite or tick exposure within one month prior to onset of symptoms. A total of 206 patients fulfilled the study. Among these, we could identify 186 cases of LB (174 with EM), 18 confirmed and two probable cases of HGA and two cases of TBE. Thirteen of the HGA cases presented without fever. Furthermore, 22 of the EM patients had a sub-clinical co-infection with Anaplasma phagocytophilum, based on serology. Both TBE cases had co-infections, one with Borrelia burgdorferi and one with Anaplasma phagocytophilum. We conclude that it is important to consider several causative agents and possible co-infections in the clinical management of infectious diseases where ticks may be suspected as vectors.
3.
  • Rostami, Elham, 1979- (författare)
  • Traumatic brain injury in humans and animal models
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Traumatic brain injuries (TBI) are receiving increasing attention due to a combination of injuries related to war and sports, as well as to an increasing number of traffic accident survivors. Today the leading cause of death in young adults in industrialized nations is traumatic brain injury and in the population under 35 years, the death rate is 3.5 times that of cancer and heart disease combined. Despite a major improvement in the outcome of TBI in the acute setting, the assessment, therapeutic interventions and prevention of long-term complications remain a challenge. The challenges today are primarily related to a rapid diagnosis, identification of patient’s pathophysiological heterogeneity and to limit the secondary injuries. TBI is a complex condition that can be caused by focal or diffuse primary impacts that may initiate complex secondary neurochemical processes that proceeds over hours and days. The major secondary events include neuronal death, ischemia, excitotoxicity, mitochondrial failure, oxidative stress, oedema and inflammation. In addition, the brain’s restorative capacity involving neurotrophins, in particular brain derived neurotrophic factor (BDNF), is triggered. Animal models are necessary to gain a deeper insight into the events that follow a TBI, and to ultimately apply the findings to the clinical setting. The aim of this thesis was to identify distinct pathological processes in different types of TBI by using animal models that mimic distinct types of TBI found in patients. We investigated alterations in gene expression, serum biomarkers and secondary processes such as inflammatory response involving the complement cascade. In addition we aimed to assess the effects of heterogeneity of TBI patients, based on their genetic background, on the outcome of TBI, with specific focus on BDNF. We used animal models to mimic three major types of TBI; blast wave, penetrating and rotational acceleration TBI. We found distinct profiles of alteration in gene expression in these models. The histological findings in blast and rotational TBI indicated these injuries to be mild. The hallmark of the rotational TBI was axonal injuries found in anatomical locations comparable with clinical findings in diffuse axonal injuries (DAI) in humans. Despite the mild type of injury displayed in the histology and behavioural outcome, significant increases in the serum biomarkers Tau, S100B, NF-H and MBP were observed up to 2 weeks following the injury. The complement cascade was initiated in both penetrating and rotational TBI, detected by C1q and C3. However, the terminal pathway that generates cell death, detected by C5b9, was only activated in the penetrating TBI. This suggests that axonal injuries and secondary axotomy found in the rotational TBI are not complement mediated. In order to investigate whether genetic heterogeneity can be used to predict injury outcome and brain plasticity following TBI, we targeted the ApoE ε4 allele and the BDNF gene. We investigated whether there was an association between the presence of the ApoE ε4 allele and BDNF polymorphisms and cognitive outcome in veterans who had suffered penetrating head injury. We found that the genetic polymorphisms of BDNF predict general intelligence following penetrating TBI. Subsequently we investigated the expression of BDNF and its receptors TrkB-full length, TrkB-truncated and p75NTR, in animals exposed to penetrating TBI. The expression of TrkB truncated and p75NTR was altered in the chronic phase. In summary, these results show the importance of categorizing the different types of TBI, not only through the use of animal models but also in the clinical setting. Each type of TBI shows distinct patterns of gene expression, behavioural outcome, and morphological changes that may be reflected in the release of serum biomarkers. In the clinical setting, the situation is further complicated by the coexistence of different types of injuries. In addition to this, the genetic background of each patient contributes to the heterogeneity of TBI pathology as well as their ability to recover. The use of distinct types of TBI models will provide essential information about the underlying pathology, which can then be applied to the clinical setting. This will contribute to the establishment of better diagnostic tools as well as more individualized treatment approaches.
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4.
  • Bjerg, Anders, et al. (författare)
  • Higher Risk of Wheeze in Female than Male Smokers. Results from the Swedish GA(2)LEN Study
  • 2013
  • Ingår i: Plos One. - 1932-6203. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Women who smoke have higher risk of lung function impairment, COPD and lung cancer than smoking men. An influence of sex hormones has been demonstrated, but the mechanisms are unclear and the associations often subject to confounding. This was a study of wheeze in relation to smoking and sex with adjustment for important confounders. Methods: In 2008 the Global Allergy and Asthma European Network (GA(2)LEN) questionnaire was mailed to 45.000 Swedes (age 16-75 years), and 26.851 (60%) participated. "Any wheeze'': any wheeze during the last 12 months. "Asthmatic wheeze'': wheeze with breathlessness apart from colds. Results: Any wheeze and asthmatic wheeze was reported by 17.3% and 7.1% of women, vs. 15.8% and 6.1% of men (both p<0.001). Although smoking prevalence was similar in both sexes, men had greater cumulative exposure, 16.2 pack-years vs. 12.8 in women (p<0.001). Most other exposures and characteristics associated with wheeze were significantly overrepresented in men. Adjusted for these potential confounders and pack-years, current smoking was a stronger risk factor for any wheeze in women aged <53 years, adjusted odds ratio (aOR) 1.85 (1.56-2.19) vs. 1.60 (1.30-1.96) in men. Cumulative smoke exposure and current smoking each interacted significantly with female sex, aOR 1.02 per pack-year (p<0.01) and aOR 1.28 (p = 0.04) respectively. Female compared to male current smokers also had greater risk of asthmatic wheeze, aOR 1.53 vs. 1.03, interaction aOR 1.52 (p = 0.02). These interactions were not seen in age >= 53 years. Discussion: In addition to the increased risk of COPD and lung cancer female, compared to male, smokers are at greater risk of significant wheezing symptoms in younger age. This became clearer after adjustment for important confounders including cumulative smoke exposure. Estrogen has previously been shown to increase the bioactivation of several compounds in tobacco smoke, which may enhance smoke-induced airway inflammation in fertile women.
5.
  • Hodgins, S., et al. (författare)
  • Individuals developing schizophrenia are hidden among adolescent substance misusers
  • 2016
  • Ingår i: Psychological Medicine. - 0033-2917. ; 46:14, s. 3041-3050
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Strategies are needed to identify youth developing schizophrenia. The present study aimed to determine whether adolescents treated for substance misuse were at elevated risk to develop schizophrenia, whether this risk has changed since the late 1960s, and whether substance misuse in adolescence predicted poorer outcomes through adulthood. Method In a Swedish city, since the mid-1960s there has been only one clinic for adolescent substance misuse. Three samples from this clinic were studied: 1992 individuals treated from 1968 to 1971 followed to age 50 years; 1576 treated from 1980 to 1984 followed to age 35 years; and 180 treated in 2004 followed to age 22 years. Each clinical sample was matched on age, sex and place of birth to an equal, or larger, number of randomly selected individuals from the general population. Schizophrenia, substance use disorders, physical disorders related to substance misuse, criminal convictions, poverty and death were identified using national registers. Results Individuals treated for substance misuse in adolescence were at increased risk to subsequently develop schizophrenia: in males the increase was approximately four-fold and in females between five- and seven-fold. There was no difference in risk for those treated in 1968-1971 and from 1980 to 1984 when cannabis use increased from 37.6% to 49.8% of the clinical samples. Among males who developed schizophrenia, treatment for substance misuse was associated with increased risk of substance use disorders and criminal convictions through adulthood. Conclusions Treatment programmes for adolescents misusing substances include a disproportionate number developing schizophrenia. Early detection and treatment have the potential to improve long-term outcomes.
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6.
  • Magnusson, Marie, et al. (författare)
  • A placebo-controlled study of retinal blood flow changes by pentoxifylline and metabolites in humans.
  • 2006
  • Ingår i: British Journal of Clinical Pharmacology. - John Wiley and Sons Inc.. - 1365-2125. ; 61:2, s. 138-147
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: To investigate the possible effects of pentoxifylline metabolites on retinal blood flow in humans. METHODS: A randomized, placebo-controlled, four-period cross-over study that was observer blinded and partly blinded for the eight participants. On one occasion a placebo was given as an intravenous (i.v.) infusion over 100 min. On the other three occasions pentoxifylline was administered as i.v. infusions over 100 min at a rate of 3 mg min(-1). Before two of the pentoxifylline infusions the subjects were pretreated with either ciprofloxacin or rifampicin. Retinal blood flow was measured by scanning laser doppler flowmetry (SLDF) in a selected area of the central temporal retina before, during and until 5 h after the end of infusion. Blood samples for concentration analyses of pentoxifyllin, R-M1, S-M1, M4 and M5 were taken serially and areas under the curves (AUCs) were calculated. Linear mixed models were used for the statistical analyses. RESULTS: Mean AUCs (ng h ml(-1)) were significantly increased for pentoxifylline (1964 vs. 1453) and S-M1 (5804 vs. 4227), but not R-M1 when pentoxifylline was co-administered with ciprofloxacin. The mean AUC for M5 was significantly reduced when subjects were pretreated with rifampicin (2041 vs. 3080). Pentoxifylline with and without pretreatment with rifampicin significantly increased retinal blood flow assessed as mean flow, pulsation (i.e. 1-systole/diastole), and diastolic flow (but not during systole), compared with placebo. The increases over placebo were more pronounced on diastolic flow, 9.7% (95% confidence interval 4.2, 15.5) than on mean flow, 4.6% (1.1, 8.3) after pentoxifylline administration. With pentoxifylline after rifampicin pretreatment the corresponding differences were 11.7% (5.8, 17.9) and 5.1% (1.4, 7.8) over placebo, respectively. After co-administration of pentoxifylline and ciprofloxacin we saw only a nonsignificant trend towards increased flow during diastole, but a significant decrease in pulsation. When AUCs for pentoxifylline and its metabolites were used as regressor variables to retinal mean flow we found that pentoxifylline, R-M1 and M5 had coefficients with a positive sign indicating that they enhanced the retinal blood flow. In contrast, S-M1 and M4 had coefficients with negative sign and thus appeared to decrease the blood flow in subjects treated with pentoxifylline. CONCLUSION: The R-M1 and M5 metabolites of pentoxifylline contributed significantly to the effects of pentoxifylline on retinal blood flow.
7.
  • Newson, R. B., et al. (författare)
  • The association of asthma, nasal allergies, and positive skin prick tests with obesity, leptin, and adiponectin
  • 2014
  • Ingår i: Clinical and Experimental Allergy. - Wiley-Blackwell. - 0954-7894. ; 44:2, s. 250-260
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cross-sectional and longitudinal reports show that obese adults have more asthma than non-obese adults. A proposed mechanism is via effects of adipokines (leptin and adiponectin) on the immune system.OBJECTIVE: We wished to measure the associations of asthma and other atopic diseases with serum adipokine levels and to find whether the associations with asthma were strong enough to rule out the possibility that they are secondary to the association of fatness measures with asthma.METHODS: The Global Asthma and Allergy Network of Excellence (GA(2) LEN) clinical follow-up survey is a clinical survey, embedded in a larger multi-centre cross-sectional postal survey, involving, with a case/control design, enrichment of the sample with subjects with asthma and chronic rhinosinusitis (CRS). We recorded serum leptin or adiponectin in 845 men and 1110 women in 15 centres and also anthropometric measures of fatness including body mass index and waist/hip ratio, current asthma, and specific skin prick and IgE sensitisation. We used inverse sampling-probability-weighted rank and regression statistics to measure population associations of disease outcomes with adipokines in males and females, adjusting for confounders (area, age, smoking history, and number of elder siblings) and also mutually adjusting associations with adipokines and fatness measures.RESULTS: One thousand nine hundred and fifty-five subjects aged 16-77 years had information on leptin or adiponectin levels. Leptin and leptin/adiponectin ratio were positively associated with the level of asthma, especially in females (Somers' D of leptin by asthma score, 0.20; 95% CI, 0.08-0.30; P = 0.00079). These associations were attenuated after adjusting for confounders and became non-significant after additionally adjusting for fatness measures and multiple comparisons.CONCLUSIONS AND CLINICAL RELEVANCE: Asthma levels are positively associated with serum leptin. However, we cannot rule out the possibility that this association is secondary to associations of both with fatness measures.
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8.
  • Adolfsson, Jan, et al. (författare)
  • Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005 : Data from the national prostate cancer register in Sweden
  • 2007
  • Ingår i: Scandinavian Journal of Urology and Nephrology. - Stockholm : Taylor & Francis. - 0036-5599. ; 41:6, s. 456-477
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. Material and methods. Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. Results. In total, 72 028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of >100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score ≤6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged ≥75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. Conclusions. All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer
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9.
  • Agnew, L., et al. (författare)
  • FACTORS ASSOCIATED WITH WORK ABILITY IN PATIENTS WITH CHRONIC WHIPLASH-ASSOCIATED DISORDER GRADE II-III: A CROSS-SECTIONAL ANALYSIS
  • 2015
  • Ingår i: Journal of Rehabilitation Medicine. - Foundation for Rehabilitation Information. - 1650-1977. ; 47:6, s. 546-551
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the factors related to self-perceived work ability in patients with chronic whiplash-associated disorder grades II-III. Design: Cross-sectional analysis. Patients: A total of 166 working age patients with chronic whiplash-associated disorder. Methods: A comprehensive survey collected data on work ability (using the Work Ability Index); demographic, psychosocial, personal, work- and condition-related factors. Forward, stepwise regression modelling was used to assess the factors related to work ability. Results: The proportion of patients in each work ability category were as follows: poor (12.7%); moderate (39.8%); good (38.5%); excellent (9%). Seven factors explained 65% (adjusted R-2 = 0.65, p less than 0.01) of the variance in work ability. In descending order of strength of association, these factors are: greater neck disability due to pain; reduced self-rated health status and health-related quality of life; increased frequency of concentration problems; poor workplace satisfaction; lower self-efficacy for performing daily tasks; and greater work-related stress. Conclusion: Condition-specific and psychosocial factors are associated with self-perceived work ability of individuals with chronic whiplash-associated disorder.
10.
  • Bohman, B., et al. (författare)
  • Infrequent attention to dietary and physical activity behaviours in conversations in Swedish child health services
  • 2013
  • Ingår i: Acta Paediatrica. - Wiley-Blackwell. - 0803-5253. ; 102:5, s. 520-524
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To investigate conversations between nurses and parents in Swedish child health services and to assess to what extent attention is directed towards dietary and physical activity behaviours in children.Methods: Twenty-three nurses audio-recorded one session each. Recordings were assessed and topics were classified according to predetermined categories.Results: The three most frequent topics of conversation concerned physical examinations of the child (30% of session time), talking to the child to establish or maintain contact and interest (15%), and development of language skills (12%). Dietary habits came on fourth place (10%), and physical activity ranked 14 (4%).Conclusion: Attention to dietary and physical activity behaviours in children is infrequent in Swedish child health services. Concern is raised about the efficacy of prevention efforts against childhood obesity.
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