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Sökning: hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Klinisk medicin) hsv:(Endokrinologi och diabetes) > Umeå universitet

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1.
  • Pourhamidi, Kaveh, et al. (författare)
  • Evaluation of clinical tools and their diagnostic use in distal symmetric polyneuropathy
  • 2014
  • Ingår i: Primary care diabetes. - : Elsevier. - 1878-0210 .- 1751-9918. ; 8:1, s. 77-84
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: To compare the diagnostic usefulness of tuning fork, monofilament, biothesiometer and skin biopsies in peripheral neuropathy in individuals with varying glucose metabolism.METHODS: Normoglycaemic, impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) individuals were recruited. Nerve conduction studies (NCS) and thermal threshold tests were performed. Vibrotactile sense was tested with a biothesiometer and a 128-Hz tuning fork. Touch/pressure perception was examined with a 10-g monofilament. Skin biopsies were performed and intraepidermal nerve fibres were quantified. Distal symmetric polyneuropathy (DSPN) was defined as neuropathy disability score ≥2 and abnormal NCS. Thermal threshold tests were used to define small nerve fibre neuropathy (sDSPN) in cases where NCS (large nerve fibres) were normal.RESULTS: The prevalence of DSPN and sDSPN in the whole group (n=119) was 18% and 23%, respectively. For the biothesiometer, a cut-off of ≥24.5V had a sensitivity of 82% and specificity of 70% (AUC=0.81, 95% CI 0.71-0.91) when evaluating DSPN. An intraepidermal nerve fibre density cut-off of ≤3.39fibres/mm showed a sensitivity of 74% and specificity of 70% in the detection of sDSPN, whereas the sensitivity of the tuning fork and the biothesiometer were relatively low, 46% and 67%, respectively. When combining skin biopsies with the tuning fork, 10 more sDSPN cases were identified. Adding skin biopsy to the combination of the tuning fork and biothesiometer increased the sensitivity of finding sDSPN cases, but not DSPN, from 81% to 93%.CONCLUSION: Using a biothesiometer in clinical routine might be a sensitive method to detect large nerve fibre dysfunction in the lower extremity, whereas skin biopsies in combination with methods measuring vibrotactile sense could increase the diagnostic sensitivity of detecting peripheral neuropathy at an early stage.
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2.
  • Pourhamidi, Kaveh, et al. (författare)
  • Heat shock protein 27 concentrations are lower in patientswith type 1 diabetes mellitus than in healthy controls andcorrelates with large nerve fibre dysfunction
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Objective Heat shock protein 27 (HSP27) may contribute to the survival of neurons. Our aims were to study whether HSP27 concentrations differ between individuals with and without type 1 diabetes, and evaluate the relationship between the progression of peripheral nerve dysfunction and HSP27 concentrations.Research Design and Methods Type 1 diabetes patients (n=27, 41% women; mean age 41±8 years) were recruited in 1992 with a follow-up in 2005; serum HSP27 concentrations were determined in baseline and follow-up samples and compared to non-diabetic controls (n=397, 34% women; mean age 43±14 years). The type 1 diabetes patients underwent nerve conduction studies and thermal and vibration perception threshold tests at baseline and at follow-up. Reference data was used to standardise results for age, height and sex by calculating the Z-scores. Delta changes in HSP27 (follow-up HSP27 – baseline HSP27) and small and large nerve fibre function were used for correlation analyses.Results Type 1 diabetes patients had lower HSP27 concentrations at baseline (mean HSP27547 pg/ml, 95% CI 421, 711) and at follow-up (mean HSP27 538 pg/ml, 95% CI 417,693) compared to healthy controls (mean HSP27 785 pg/ml, 95% CI 732, 842; p<0.05 for both comparisons). Deteriorating large nerve fibre function correlated with delta HSP27 concentrations in type 1 diabetes (r=0.50, p=0.01).Conclusions Patients with type 1 diabetes had lower HSP27 concentrations than non-diabetic controls and progression of large nerve fibre dysfunction correlated with decreasing HSP27 concentrations during the follow-up period. This could be indicative ofinsufficient neuroprotection in type 1 diabetes.
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3.
  • Pourhamidi, Kaveh, et al. (författare)
  • Heat shock protein 27 is associated with better nerve function and fewer signs of neuropathy
  • 2011
  • Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 54:12, s. 3143-3149
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis High levels of serum heat shock protein 27 (sHSP27) have been associated with distal symmetric polyneuropathy in patients with type 1 diabetes. Our objective was to investigate the association between sHSP27, neuropathic signs and nerve function in individuals with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and type 2 diabetes.Methods Participants were recruited consecutively from the population-based Vasterbotten Intervention Program (NGT, n=39, IGT, n=29, and type 2 diabetes, n=51) and were matched for age and sex. sHSP27 levels were measured and nerve conduction studies were performed (peroneal and sural nerves). z Scores for each nerve conduction measure were calculated and compiled into a composite z score for the leg. Neuropathy disability score (NDS) was used to assess neuropathic signs.Results Patients with diabetes had significantly lower sHSP27 levels (geometric mean sHSP27 206 pg/ml, 95% CI 142, 299) than those with IGT (geometric mean sHSP27 455 pg/ml, 95% CI 319, 650, p<0.05) and controls (geometric mean sHSP27 361 pg/ml, 95% CI 282, 461, p<0.05). Participants with few signs of neuropathy (first tertile, NDS <= 2) had significantly higher sHSP27 levels (geometric mean sHSP27 401 pg/ml, 95% CI 310, 520) than participants with many signs (third tertile, NDS >= 7) (geometric mean sHSP27 192 pg/ml, 95% CI 128, 288, p=0.007). The highest sHSP27 tertile was associated with better nerve function, adjusted for age, sex, statin medication and HbA(1c) (OR 2.51, 95% CI 1.25, 5.05, p<0.05).Conclusions/interpretation High sHSP27 levels were associated with better nerve function and fewer neuropathic signs in NGT, IGT and type 2 diabetes.
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4.
  • Pourhamidi, Kaveh, 1985- (författare)
  • Peripheral nerve function : metabolic features, clinical assessment, and heat shock protein 27
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Peripheral neuropathy is a common complication among patients with diabetes mellitus, but whether peripheral neuropathy is present in individuals with impaired glucose tolerance (IGT) is debatable. In order to identify and diagnose peripheral neuropathy correctly, it is important to evaluate diagnostic tools that can be implemented in routine health care to assess both large and small nerve fibre function. There is currently limited knowledge about neuroprotective factors that could be useful for measuring peripheral nerve function in individuals at risk of developing neuropathy such as those with diabetes mellitus. Thus, studies are needed to investigate potential neuroprotective factors in relation to peripheral nerve function in humans.Objectives: The overall goal of this thesis was to study the metabolic features and clinical assessment of peripheral nerve function and the potential relationship between the neuroprotective factor heat shock protein 27 (HSP27) and peripheral nerve function.Methods: Thirty-nine participants with normal glucose tolerance (NGT) and 29 participants with IGT were recruited from the population-based Västerbotten Intervention Programme in 2003–2004. Patients with type 2 diabetes mellitus (T2DM, n = 51) were recruited from primary health care centres. NGT and IGT individuals underwent two separate oral glucose tolerance tests to verify their glucose status. The peripheral nerve function in the lower limb was assessed by nerve conduction studies, neuropathy disability scoring, quantitative sensory tests, and skin biopsies with subsequent quantification of intraepidermal nerve fibre density (IENFD). The concentrations of HSP27 in serum were determined in the NGT, IGT, and T2DM individuals. Patients with type 1 diabetes mellitus (T1DM) were recruited from the Diabetes Clinic, Skåne University Hospital in Malmö, Sweden (n = 27) in 1992 and were followed-up in 2005. Baseline and follow-up concentrations of HSP27 were determined in T1DM patients as well as in healthy non-diabetic controls (n = 397). The T1DM patients underwent nerve conduction studies and thermal and vibration perception threshold tests at baseline and at follow-up. Delta changes in HSP27 concentrations and small and large nerve fibre function were calculated.Results: There was no difference between IGT and NGT in sural nerve conduction, intraepidermal nerve fibre density, or thermal thresholds. The biothesiometer had a sensitivity of 82% and a specificity of 72% in identifying peripheral neuropathy with a cut-off value of ≥24.5 V at the medial malleolus. Adding the quantification of IENFD to the combination of the tuning fork and biothesiometer increased the diagnostic sensitivity from 81% to 95%, the negative predictive value from 87% to 94%, and the positive likelihood ratio from 1.8 to 1.9 when identifying small nerve fibre dysfunction. T2DM patients had lower HSP27 concentrations (mean HSP27 = 412 pg/mL, 95% CI 284–598 pg/mL) than NGT (mean HSP27 = 722 pg/mL, 95% CI 564–922 pg/mL) and IGT (mean HSP27 = 1010 pg/mL, 95% CI 638–1300 pg/mL) individuals (p <0.05 for both comparisons). T1DM patients had lower HSP27 concentrations at baseline (mean HSP27 = 547 pg/mL, 95% CI 421–711 pg/mL) and at follow-up (mean HSP27 = 538 pg/mL, 95% CI 417–693 pg/mL) compared to healthy controls (mean HSP27 = 785 pg/mL, 95% CI 732–842 pg/mL), p <0.05 for both comparisons). High concentrations of HSP27 were associated with better large nerve fibre function (Odds ratio = 2.51, 95% CI 1.25–5.05, p <0.05). Deteriorating large nerve fibre function correlated with decreasing HSP27 concentrations over time in T1DM patients (r = 0.50, p = 0.01).Conclusions: Measures of large and small nerve fibre function in IGT individuals do not differ significantly from NGT individuals. The existence of peripheral neuropathy as a consequence of IGT is not likely, and extensive control of neuropathy in IGT individuals is not advocated by this thesis. The biothesiometer is a useful clinical tool to identify peripheral neuropathy in routine health care. Quantification of IENFD using skin biopsies in combination with methods measuring vibrotactile sense, such as the biothesiometer and the tuning fork, increase the diagnostic usefulness of identifying small nerve fibre dysfunction. High HSP27 concentrations are associated with better peripheral large nerve fibre function. Patients with diabetes mellitus have lower HSP27 concentrations than healthy non-diabetic controls, and deterioration of large nerve fibre function correlates with a decrease in HSP27 concentrations over time in T1DM. This could be indicative of insufficient neuroprotection in patients with diabetes mellitus.
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5.
  • Taddei, C, et al. (författare)
  • Repositioning of the global epicentre of non-optimal cholesterol
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
  • Tidskriftsartikel (refereegranskat)abstract
    • High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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6.
  • Eriksson, D, et al. (författare)
  • Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
  • 2016
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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7.
  • Lewerin, Catharina, 1961, et al. (författare)
  • High plasma osteocalcin is associated with low blood haemoglobin in elderly men: the MrOS Sweden Study
  • 2016
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 280:4, s. 398-406
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: It has been suggested that osteoblasts are involved in the regulation of haematopoietic stem cells. Whether osteocalcin, which is derived from osteoblasts and is metabolically active, influences blood haemoglobin (Hb) levels is not known. OBJECTIVE: To determine whether plasma osteocalcin is a determinant of Hb in elderly men. METHODS: A total of 993 men (mean age 75.3 +/- 3.2 years) participated in the population-based MrOS (osteoporotic fractures in men) study. Plasma osteocalcin concentration was evaluated in relation to Hb and adjustments were made for potential confounders (i.e. age, body mass index, erythropoietin, total oestradiol, fasting insulin, adiponectin, ferritin and cystatin C). RESULTS: Hb correlated (age adjusted) negatively with osteocalcin in the total study group (r = -0.12, P < 0.001) as well as in the subgroup of nondiabetic men (r = -0.16, P < 0.001). In nondiabetic men with higher osteocalcin levels, it was more likely that Hb would be in the lowest quartile (odds ratio per SD decrease in osteocalcin 1.32, 95% confidence interval 1.13-1.53). Quartiles of Hb were negatively associated (age adjusted) with osteocalcin (P < 0.001). Anaemic men (47/812) (Hb <130 g L-1 ) had significantly higher mean osteocalcin levels than nonanaemic men (33.9 vs. 27.1 mug L-1 , P < 0.001). In multiple stepwise linear regression analyses (adjusted for age, body mass index, total oestradiol, adiponectin, erythropoietin, fasting insulin, cystatin C, leptin, ferritin and holotranscobalamin), osteocalcin was an independent predictor of Hb concentration in nondiabetic men (P < 0.05). CONCLUSIONS: These data add further support to the evidence indicating that the bone-specific protein osteocalcin has several endocrine functions targeting the pancreas, testes, adipocytes, brain. An additional novel finding is that osteocalcin may also have a paracrine function as a regulator of haematopoiesis.
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8.
  • Brand, J. S., et al. (författare)
  • Diabetes and onset of natural menopause : results from the European Prospective Investigation into Cancer and Nutrition
  • 2015
  • Ingår i: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 30:6, s. 1491-1498
  • Tidskriftsartikel (refereegranskat)abstract
    • STUDY QUESTION: Do women who have diabetes before menopause have their menopause at an earlier age compared with women without diabetes? SUMMARY ANSWER: Although there was no overall association between diabetes and age at menopause, our study suggests that early-onset diabetes may accelerate menopause. WHAT IS KNOWN ALREADY: Today, more women of childbearing age are being diagnosed with diabetes, but little is known about the impact of diabetes on reproductive health. STUDY DESIGN, SIZE, DURATION: We investigated the impact of diabetes on age at natural menopause (ANM) in 258 898 women from the European Prospective Investigation into Cancer and Nutrition (EPIC), enrolled between 1992 and 2000. PARTICIPANTS/MATERIALS, SETTING, METHODS: Determinant and outcome information was obtained through questionnaires. Time-dependent Cox regression analyses were used to estimate the associations of diabetes and age at diabetes diagnosis with ANM, stratified by center and adjusted for age, smoking, reproductive and diabetes risk factors and with age from birth to menopause or censoring as the underlying time scale. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, no association between diabetes and ANM was found (hazard ratio (HR) = 0.94; 95% confidence interval (CI) 0.89-1.01). However, women with diabetes before the age of 20 years had an earlier menopause (10-20 years: HR = 1.43; 95% CI 1.02-2.01, <10 years: HR = 1.59; 95% CI 1.03-2.43) compared with non-diabetic women, whereas women with diabetes at age 50 years and older had a later menopause (HR = 0.81; 95% CI 0.70-0.95). None of the other age groups were associated with ANM. LIMITATIONS, REASONS FOR CAUTION: Strengths of the study include the large sample size and the broad set of potential confounders measured. However, results may have been underestimated due to survival bias. We cannot be sure about the sequence of the events in women with a late age at diabetes, as both events then occur in a short period. We could not distinguish between type 1 and type 2 diabetes. WIDER IMPLICATIONS OF THE FINDINGS: Based on the literature, an accelerating effect of early-onset diabetes on ANM might be plausible. A delaying effect of late-onset diabetes on ANM has not been reported before, and is not in agreement with recent studies suggesting the opposite association.
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9.
  • Omar, Nor Adila Mhd, et al. (författare)
  • Long-term whole-grain rye and wheat consumption and their associations with selected biomarkers of inflammation, endothelial function, and cardiovascular disease
  • 2021
  • Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 75:1, s. 123-132
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/objectives Whole-grain (WG) intake has been associated with a lowered risk of developing type 2 diabetes, cardiovascular disease, and some cancers in epidemiological studies. Reduced subclinical inflammation could be one important mechanism behind such associations. This study investigated whether high long-term WG rye and wheat intakes were associated with lower concentrations of biomarkers of inflammation, endothelial function, and protein biomarkers associated with cardiovascular disease. Subjects/methods We assessed WG intake by food frequency questionnaire (FFQ) and by measuring alkylresorcinols (ARs) in plasma and adipose tissue, respectively. Selected biomarkers in free-living 109 women and 149 men were analyzed from two clinical subcohort studies (Swedish Mammography Cohort-Clinical (SMC-C) and Cohort of Swedish Men-Clinical (COSM-C), respectively. Total WG rye and wheat (WGRnW) and the ratio of WG rye to WG rye and wheat (WGR/WGRnW) were estimated from FFQs. ARs were measured in plasma and adipose tissue by gas chromatography-mass spectrometry (GC-MS) and the biomarkers by ELISA. Results We found no consistent associations between WG intake assessed by different methods and the selected biomarkers. However, WGRnW intake was inversely associated with cathepsin S (P-trend < 0.05) and total AR and C17:0/C21:0 in plasma were inversely associated with the endostatin concentration (P-trend < 0.05) adjusted for BMI, age, and sex. Conclusion The results give limited support to the hypothesis that a high WG wheat and rye intake is associated with lower concentrations of common biomarkers of inflammation and CVD that have previously been reported inversely associated with WG intake or an overall healthy lifestyle.
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10.
  • Song, Xin, et al. (författare)
  • Obesity attenuates gender differences in cardiovascular mortality
  • 2014
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840 .- 1475-2840. ; 13, s. 144-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: To estimate cardiovascular disease (CVD) mortality in relation to obesity and gender. Methods: Data from 11 prospective cohorts from four European countries including 23 629 men and 21 965 women, aged 24 to 99 years, with a median follow-up of 7.9 years were analyzed. Hazards ratios (HR) for CVD mortality in relation to baseline body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were estimated using Cox proportional hazards models with age as the timescale. Results: Men had higher CVD mortality than women in all four BMI categories (<25.0, 25.0-29.9, 30.0-34.9 and >= 35.0 kg/m(2)). Compared with the lowest BMI category in women, multivariable adjusted HRs (95% confidence intervals) for higher BMI categories are 1.0 (0.8-1.4), 1.6 (1.1-2.1) and 2.8 (2.0-3.8) in women and 2.8 (2.2-3.6), 3.1 (2.5-3.9), 3.8 (2.9-4.9) and 5.4 (3.8-7.7) in men, respectively. Similar findings were observed for abdominal obesity defined by WC, WHR or WHtR. The gender difference was slightly smaller in obese than in non-obese individuals; but the interaction was statistically significant only between gender and WC (p = 0.02), and WHtR (p = 0.01). None of the interaction terms was significant among non-diabetic individuals. Conclusions: Men had higher CVD mortality than women across categories of anthropometric measures of obesity. The gender difference was attenuated in obese individuals, which warrants further investigation.
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