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Sökning: WFRF:(Engström Patrik)

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1.
  • André-Petersson, Lena, et al. (författare)
  • Behavior in a stressful situation, personality factors, and disease severity in patients with acute myocardial infarction: baseline findings from the prospective cohort study SECAMI (The Secondary Prevention and Compliance following Acute Myocardial Infarction-study)
  • 2011
  • Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Psychosocial stress has been identified as a risk factor in association with cardiovascular disease but less attention has been paid to heterogeneity in vulnerability to stress. The serial Color Word Test (CWT) measures adaptation to a stressful situation and it can be used to identify individuals that are vulnerable to stress. Prospective studies have shown that individuals with a maladaptive behavior in this test are exposed to an increased risk of future cardiovascular events. The aim of the present study was to investigate whether maladaptive behavior in the serial CWT alone or in combination with any specific personality dimension was associated with severity of myocardial infarction (MI). Methods: MI-patients (n = 147) completed the test and filled in a personality questionnaire in close proximity to the acute event. The results were analyzed in association with four indicators of severity: maximum levels above median of the cardiac biomarkers troponin I and creatine kinase-MB (CKMB), Q-wave infarctions, and a left ventricular ejection fraction (LVEF) <= 50%. Results: Maladaptive behavior in the serial CWT together with low scores on extraversion were associated with maximum levels above median of cardiac troponin I (OR 2.97, CI 1.08-8.20, p = 0.04) and CKMB (OR 3.33, CI 1.12-9.93, p = 0.03). No associations were found between the combination maladaptive behavior and low scores on extraversion and Q-wave infarctions or a decreased LVEF. Conclusions: Maladaptive behavior in combination with low scores on extraversion is associated with higher cardiac biomarker levels following an MI. The serial CWT and personality questionnaires could be used to identify individuals vulnerable to the hazardous effects of stress and thereby are exposed to an increased risk of a more severe infarction.
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  • Araghi, Marzieh, et al. (författare)
  • No association between moist oral snuff (snus) use and oral cancer : pooled analysis of nine prospective observational studies
  • 2021
  • Ingår i: Scandinavian Journal of Public Health. - : Sage Publications. - 1403-4948 .- 1651-1905. ; 49:8, s. 833-840
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Worldwide, smokeless-tobacco use is a major risk factor for oral cancer. Evidence regarding the particular association between Swedish snus use and oral cancer is, however, less clear. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between snus use and oral cancer.Methods: A total of 418,369 male participants from nine cohort studies were followed up for oral cancer incidence through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors.Results: During 9,201,647 person-years of observation, 628 men developed oral cancer. Compared to never-snus use, ever-snus use was not associated with oral cancer (adjusted HR 0.90, 95% CI: 0.74, 1.09). There were no clear trends in risk with duration or intensity of snus use, although lower intensity use (<= 4 cans/week) was associated with a reduced risk (HR 0.65, 95% CI: 0.45, 0.94). Snus use was not associated with oral cancer among never smokers (HR 0.87, 95% CI: 0.57, 1.32).Conclusions: Swedish snus use does not appear to be implicated in the development of oral cancer in men.
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  • Araghi, Marzieh, et al. (författare)
  • Smokeless tobacco (snus) use and colorectal cancer incidence and survival : Results from nine pooled cohorts
  • 2017
  • Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 45:8, s. 741-748
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: Although smoking is considered to be an established risk factor for colorectal cancer, the current evidence on the association between smokeless tobacco and colorectal cancer is scant and inconclusive. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess this association.METHODS: A total of 417,872 male participants from nine cohort studies across Sweden were followed up for incidence of colorectal cancer and death. Outcomes were ascertained through linkage to health registers. We used shared frailty models with random effects at the study level to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).RESULTS: During 7,135,504 person-years of observation, 4170 men developed colorectal cancer. There was no clear association between snus use and colorectal cancer overall. Exclusive current snus users, however, had an increased risk of rectal cancer (HR 1.40: 95% CI 1.09, 1.79). There were no statistically significant associations between snus use and either all-cause or colorectal cancer-specific mortality after colorectal cancer diagnosis.CONCLUSIONS: Our findings, from a large sample, do not support any strong relationships between snus use and colorectal cancer risk and survival among men. However, the observed increased risk of rectal cancer is noteworthy, and in merit of further attention.
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  • Araghi, Marzieh, et al. (författare)
  • Use of moist oral snuff (snus) and pancreatic cancer : Pooled analysis of nine prospective observational studies
  • 2017
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 141:4, s. 687-693
  • Tidskriftsartikel (refereegranskat)abstract
    • While smoking is a well-established risk factor for pancreatic cancer, the effect of smokeless tobacco is less well understood. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between Swedish snus use and the risk of pancreatic cancer. A total of 424,152 male participants from nine cohort studies were followed up for risk of pancreatic cancer through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors. During 9,276,054 person-years of observation, 1,447 men developed pancreatic cancer. Compared to never-snus use, current snus use was not associated with risk of pancreatic cancer (HR 0.96, 95% CI 0.83-1.11) after adjustment for smoking. Swedish snus use does not appear to be implicated in the development of pancreatic cancer in men. Tobacco smoke constituents other than nicotine or its metabolites may account for the relationship between smoking and pancreatic cancer. What's new? While smoking is a well-established risk factor for pancreatic cancer, the effect of smokeless tobacco is less well understood. Smokeless tobacco like snus yields lower exposure to tobacco carcinogens compared with smoking, because it does not undergo combustion, but delivers an equivalent dose of nicotine. Using pooled individual data from the Swedish Collaboration on Health Effects of Snus Use, here the authors show that Swedish snus use does not appear to be implicated in the development of pancreatic cancer in men. Tobacco smoke constituents other than nicotine or its metabolites may account for the relationship between smoking and pancreatic cancer.
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  • Bender, Johanna, 1975, et al. (författare)
  • Structure and dynamics of a sponge phase in the methyl delta-aminolevulinate/monoolein/water/propylene glycol system
  • 2008
  • Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 1095-7103 .- 0021-9797. ; 17:2, s. 577-584
  • Tidskriftsartikel (refereegranskat)abstract
    • The structural effect caused by the addition of up to 16% (w/w) of the hydrochloride salt of delta-aminolevulinic acid (ALA, HOOC-CH(2)-CH(2)-CO-CH(2)-NH(2)HCl) or its methyl ester (m-ALA) to the sponge phase formed of monoolein/water/propylene glycol was investigated by means of crossed polarizers, small angle X-ray diffraction (SAXD) and nuclear magnetic resonance diffusometry (NMRD). Inspection with crossed polarizers revealed that additions of 4-16% (w/w) m-ALA transformed the isotropic bicontinuous sponge phase partly (4-10%) or completely (13 and 16%) into an anisotropic lamellar phase, indicating that m-ALA has a flattening effect on the bilayer curvature. The addition of 16% (w/w) ALA did not show any effect on the sponge phase. By addition of water to the anisotropic m-ALA samples, isotropic liquids were re-formed. The SAXD data for the isotropic liquids showed a diffuse Bragg peak and the NMRD self-diffusion coefficients for the drug (m-ALA) and the components of the original sponge phase (monoolein, water and propylene glycol) were shown to be essentially constant for 0-16% (w/w) added m-ALA. These results confirmed the hypothesis that the re-formed isotropic phases were indeed sponge phases. Water, for example, showed a diffusion coefficient of 3.1-3.9x10(-10)m(2)s(-1) in the sponge phase, compared to 5.3-5.7x10(-10)m(2)s(-1) in relevant water/propylene glycol solutions or 2.3x10(-9)m(2)s(-1) in pure water. The reduction can be explained as a consequence of the microstructure (congruent monoolein bilayer) of the sponge phase and of the viscosity effect caused by propylene glycol and m-ALA.
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  • Boivie, Patrik, 1976- (författare)
  • Cerebrovascular accidents associated with aortic manipulation during cardiac surgery
  • 2005
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Despite the successful development in cardiac surgery, cerebrovascular accidents (CVA) remain a devastating complication. Aortic atherosclerosis has been identified as a major risk factor for CVA. The present thesis addresses this question in relation to aortic manipulation during cardiac surgery, being divided into a clinical (I-II) and an experimental part (III-V). Material and methods: Consecutive cardiac surgery cases (n=2641) were analyzed. Patients with CVA were extracted from a database designed to monitor clinical symptoms. Patient records were used to confirm clinical data and diagnosis. Subdivision was made into three groups: control subjects, immediate, and delayed CVA, being analyzed for neurological symptoms (I). Patients with CVA who also had been investigated with computer tomography (CT) (n=77) were further evaluated in terms of hemispheric and vascular distribution of lesions. The CT-findings were compared with CVA symptoms (II). An aortic perfusion model was developed using cadaver aorta onto which multiple cross-clamp manipulations were applied (III). Washout samples of perfusate were analyzed by computerized image processing and with subdivision into different particle spectra. The model was further developed with the introduction of intraluminal manipulation from cannula and intra-aortic filter (IV). A technique for macro-anatomic mapping of plaque distribution of cadaver thoracic aorta was developed (V). Variation in plaque density was analyzed in different anatomical segments, monitored by digital image analysis. Hazards associated with surgical manipulation were studied by superimposing cannulation and cross-clamp sites onto the aortic maps in a blinded fashion. Results: The incidence of immediate and delayed CVA was 3.0% and 0.9%, respectively. Aortic quality was a strongly associated with immediate but not delayed CVA. Left-sided symptoms of immediate CVA were significantly more frequent than of the contra-lateral side. Positive signs on CT were seen in 66% of the CVA patients. Right-hemispheric lesions were more frequent compared with the contra-lateral side and the middle-cerebral artery territory dominated. Aortic cross-clamping produced a substantial output of particulate matter. Manipulation by intra-aortic filter produced a significant washout of embolic particles that escaped the filter, although some particles were captured. Cannulation was an additional source of embolic material. In terms of plaque distribution was the anterior wall of the ascending part and arch of the aorta more affected than its posterior side. However, observing a plaque in the anterior wall of this aortic segment predicted to 83% a concomitant plaque in the posterior wall. Increased age correlated positively with plaque density. The theoretical chance of interfering with a plaque during cannulation and/or clamp positioning was 45.8%. Conclusions: Both CT scans and clinical symptoms confirmed that CVA after cardiac surgery had a right-hemispheric predominance. The perfusion model resulted in a profound output of material during cross-clamp maneuvers. The intra-aortic filter successfully collected particles but also generated embolic debris on its own. Aortic cannulation was an additional source of embolic debris. Plaques were frequently found in the cadaveric aorta, and there was a high risk of plaque interference during surgical manipulation. As expected, plaque density was age-dependent.
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  • Boivie, Patrik, et al. (författare)
  • Embolic material generated by multiple aortic crossclamping : a perfusion model with human cadaveric aorta
  • 2003
  • Ingår i: Journal of Thoracic and Cardiovascular Surgery. - 0022-5223 .- 1097-685X. ; 125:6, s. 1451-1460
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Atherosclerosis of the ascending aorta and use of aortic crossclamping are risk factors for neurologic injury during cardiac surgery. OBJECTIVES: Repeated aortic manipulation is part of the surgical approach to most cardiac operations. The aim of this study was to assess the amount and size of particulate matter that is dislodged from the aortic wall as a function of repeated aortic crossclamping. METHODS: In 10 subjects undergoing autopsy the aorta was dissected and mounted in a perfusion model. The ascending aorta was crossclamped and washed out 10 times, with the perfusate collected in aliquots (1 to 10). The aliquots were examined by computerized image processing, both macroscopically and under the microscope for calcified and cellular material. RESULTS: Aortic crossclamping produced substantial output of particulate matter. After repeated aortic crossclamping the number of particles decreased (P =.012) and approached the baseline for aliquots 6 to 10. The average particle diameter was 0.63 +/- 0.03 mm, with a maximum of 4.74 mm. Similar variability in particle outputs were recorded microscopically, with findings of both calcified and cellular material. Nine of 10 aortas had calcifications seen during simple visual inspection. CONCLUSIONS: The washouts of dislodge material at aortic crossclamping had embolic potential. During the initial aortic crossclamping procedures the amount of particles was substantial, both macroscopically and microscopically. On the microscopic scale noncalcified cellular debris represents a significant pool of embolic material. Repeated aortic crossclamping reduced the amount of particles. These findings question surgical techniques associated with repeated aortic crossclamping.
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  • Boivie, Patrik, et al. (författare)
  • Intraluminal aortic manipulation by means of intra-aortic filter, cannulation, and external clamp maneuvers evaluated versus dislodged embolic material.
  • 2006
  • Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier BV. - 0022-5223 .- 1097-685X. ; 131:2, s. 283-289
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Aortic atherosclerosis is an important risk factor for cerebrovascular accidents in cardiac surgery. An intra-aortic filter might reduce this risk. We aimed to analyze the risks for emboli associated with intraluminal aortic manipulation and intra-aortic filter handling in relation to cannulation and external clamp maneuvers. METHODS: A model was designed with a cadaver aorta and retrograde perfusion (n = 16). A crossclamp was positioned on the ascending aorta and repeatedly opened under pressure to collect aliquots with dislodged particles. Cannulation was performed after 10 clamp maneuvers, followed by positioning and removing the intra-aortic filter, with each step followed by a washout sequence to collect perfusate. The removed filter was also analyzed. Evaluation was by means of digital image analysis, with differentiation of particles into different spectra. RESULTS: Intra-aortic filter manipulation produced a significant washout of embolic particles; in particular, this was seen for the macroscopic cellular spectrum (P = .006 and P = .002 for filter insertion and removal, respectively). Particles were also found to be collected by the filter (P = .004). In addition, cannulation and aortic crossclamp manipulation generated a notable number of particles (P = .001 and P = .013, respectively). CONCLUSIONS: The intra-aortic filter collects material during aortic manipulation. However, intraluminal aortic manipulation from filter handling can also dislodge particles, possibly related to shedding of intimal debris. This is in addition to substantial amounts of particles that are generated by aortic cannulation and aortic crossclamping.
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  • Boivie, Patrik, et al. (författare)
  • Side differences in cerebrovascular accidents after cardiac surgery : a statistical analysis of neurologic symptoms and possible implications for anatomic mechanisms of aortic particle embolization.
  • 2005
  • Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier BV. - 0022-5223 .- 1097-685X. ; 129:3, s. 591-598
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Aortic manipulation and particle embolization have been identified to cause cerebrovascular accidents in cardiac surgery. Recent data suggest that left-hemispheric cerebrovascular accident (right-sided symptoms) is more common, and this has been interpreted as being caused by aortic cannula stream jets. Our aim was to evaluate symptoms of cerebrovascular accident and side differences from a retrospective statistical analysis. METHODS: During a 2-year period, 2641 consecutive cardiac surgery cases were analyzed. Patients positive for cerebrovascular accident were extracted from a database designed to monitor clinical symptoms. A protocol was used to confirm symptom data with the correct diagnosis in patient records. Patients were subdivided into 3 groups: control, immediate cerebrovascular accident, and delayed cerebrovascular accident. RESULTS: Among pooled patients, immediate and delayed cerebrovascular accidents were 3.0% and 0.9%, respectively. The expected predisposing factors behind immediate cerebrovascular accidents were significant, although the type of operation affected this search. Aortic quality was a strong predictor ( P < .001). The rate of delayed cerebrovascular accident was unaffected by surgery group. Left-sided symptoms of immediate cerebrovascular accident were approximately twice as frequent ( P = .016) as on the contralateral side. This phenomenon was observed for pooled patients and for isolated coronary bypass procedures (n = 1882; P = .025). CONCLUSIONS: Immediate cerebrovascular accident and aortic calcifications are linked. The predominance of left-sided symptoms may suggest that aortic manipulation and anatomic mechanisms in the aortic arch are more likely to cause cerebrovascular accidents than effects from cannula stream jets.
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  • Boivie, Patrik, et al. (författare)
  • Size distribution of embolic material produced at aortic cross-clamp manipulation
  • 2010
  • Ingår i: Scandinavian Cardiovascular Journal. - London, UK : Informa Plc.. - 1401-7431 .- 1651-2006. ; 44:6, s. 367-372
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The association between aortic atherosclerosis and neurological damage during cardiac surgery is well recognized. The purpose was here to analyze the size distribution of particles produced at cross-clamp manipulation of the ascending aorta. Design: A human cadaveric aortic perfusion model of retrograde design was applied (n 27). With this model, washout samples were collected from the pressurized ascending aorta during cross clamp manipulation. Before the experiment, the aorta was flushed to remove debris and with a baseline sample collected. The cross-clamp was opened to collect ten repeated aliquots with dislodged particles. Collected washout samples were evaluated by digital image analysis and microscopy. Results: Cross-clamping produced a significant output of particles, which was seen for size intervals of 1 mm and smaller (p 0.002 to p 0.022). In all size intervals the particle output correlated with the degree of overall aortic calcification(p 0.002 to p 0.025). The model generated substantially more small-size particles than large debris (p 0.010). Conclusions: Aortic clamping was here verified to dislodge aortic debris which correlated with the degree of observed calcification. Macroscopic particles were few. In contrast, cross-clamping produced substantial numbers of small-size particles. These findings emphasize microembolic risks associated with cross-clamping of atherosclerotic vessels.
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  • Brynolfsson, Patrik, et al. (författare)
  • Technical note : adapting a GE SIGNA PET/MR scanner for radiotherapy
  • 2018
  • Ingår i: Medical physics (Lancaster). - : Wiley-Blackwell Publishing Inc.. - 0094-2405. ; 45:8, s. 3546-3550
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Simultaneous collection of PET and MR data for radiotherapy purposes are useful for, for example, target definition and dose escalations. However, a prerequisite for using PET/MR in the radiotherapy workflow is the ability to image the patient in treatment position. The aim of this work was to adapt a GE SIGNA PET/MR scanner to image patients for radiotherapy treatment planning and evaluate the impact on signal-to-noise (SNR) of the MR images, and the accuracy of the PET attenuation correction. Method: A flat tabletop and a coil holder were developed to image patients in the treatment position, avoid patient contour deformation, and facilitate attenuation correction of flex coils. Attenuation corrections for the developed hardware and an anterior array flex coil were also measured and implemented to the PET/MR system to minimize PET quantitation errors. The reduction of SNR in the MR images due to the added distance between the coils and the patient was evaluated using a large homogenous saline-doped water phantom, and the activity quantitation errors in PET imaging were evaluated with and without the developed attenuation corrections. Result: We showed that the activity quantitation errors in PET imaging were within ±5% when correcting for attenuation of the flat tabletop, coil holder, and flex coil. The SNR of the MRI images were reduced to 74% using the tabletop, and 66% using the tabletop and coil holders. Conclusion: We present a tabletop and coil holder for an anterior array coil to be used with a GE SIGNA PET/MR scanner, for scanning patients in the radiotherapy work flow. Implementing attenuation correction of the added hardware from the radiotherapy setup leads to acceptable PET image quantitation. The drop in SNR in MR images may require adjustment of the imaging protocols.
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  • Byhamre, Marja Lisa, et al. (författare)
  • Swedish snus use is associated with mortality : a pooled analysis of eight prospective studies
  • 2020
  • Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 49:6, s. 2041-2050
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The health consequences of the use of Swedish snus, including its relationship with mortality, have not been fully established. We investigated the relationship between snus use and all-cause and cause-specific mortality (death due to cardiovascular diseases, cancer diseases and all other reasons, respectively) in a nationwide collaborative pooling project.METHODS: We followed 169 103 never-smoking men from eight Swedish cohort studies, recruited in 1978-2010. Shared frailty models with random effects at the study level were used in order to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of mortality associated with snus use.RESULTS: Exclusive current snus users had an increased risk of all-cause mortality (aHR 1.28, 95% CI 1.20-1.35), cardiovascular mortality (aHR 1.27, 95% CI 1.15-1.41) and other cause mortality (aHR 1.37, 95% CI 1.24-1.52) compared with never-users of tobacco. The risk of cancer mortality was also increased (aHR 1.12, 95% CI 1.00-1.26). These mortality risks increased with duration of snus use, but not with weekly amount.CONCLUSIONS: Snus use among men is associated with increased all-cause mortality, cardiovascular mortality, with death from other causes and possibly with increased cancer mortality.
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  • Carrasquilla, Germán D, et al. (författare)
  • Postmenopausal hormone therapy and risk of stroke : A pooled analysis of data from population-based cohort studies.
  • 2017
  • Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 14:11
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Recent research indicates a favourable influence of postmenopausal hormone therapy (HT) if initiated early, but not late, on subclinical atherosclerosis. However, the clinical relevance of timing of HT initiation for hard end points such as stroke remains to be determined. Further, no previous research has considered the timing of initiation of HT in relation to haemorrhagic stroke risk. The importance of the route of administration, type, active ingredient, and duration of HT for stroke risk is also unclear. We aimed to assess the association between HT and risk of stroke, considering the timing of initiation, route of administration, type, active ingredient, and duration of HT.METHODS AND FINDINGS: Data on HT use reported by the participants in 5 population-based Swedish cohort studies, with baseline investigations performed during the period 1987-2002, were combined in this observational study. In total, 88,914 postmenopausal women who reported data on HT use and had no previous cardiovascular disease diagnosis were included. Incident events of stroke (ischaemic, haemorrhagic, or unspecified) and haemorrhagic stroke were identified from national population registers. Laplace regression was employed to assess crude and multivariable-adjusted associations between HT and stroke risk by estimating percentile differences (PDs) with 95% confidence intervals (CIs). The fifth and first PDs were calculated for stroke and haemorrhagic stroke, respectively. Crude models were adjusted for age at baseline only. The final adjusted models included age at baseline, level of education, smoking status, body mass index, level of physical activity, and age at menopause onset. Additional variables evaluated for potential confounding were type of menopause, parity, use of oral contraceptives, alcohol consumption, hypertension, dyslipidaemia, diabetes, family history of cardiovascular disease, and cohort. During a median follow-up of 14.3 years, 6,371 first-time stroke events were recorded; of these, 1,080 were haemorrhagic. Following multivariable adjustment, early initiation (<5 years since menopause onset) of HT was associated with a longer stroke-free period than never use (fifth PD, 1.00 years; 95% CI 0.42 to 1.57), but there was no significant extension to the time period free of haemorrhagic stroke (first PD, 1.52 years; 95% CI -0.32 to 3.37). When considering timing as a continuous variable, the stroke-free and the haemorrhagic stroke-free periods were maximal if HT was initiated approximately 0-5 years from the onset of menopause. If single conjugated equine oestrogen HT was used, late initiation of HT was associated with a shorter stroke-free (fifth PD, -4.41 years; 95% CI -7.14 to -1.68) and haemorrhagic stroke-free (first PD, -9.51 years; 95% CI -12.77 to -6.24) period than never use. Combined HT when initiated late was significantly associated with a shorter haemorrhagic stroke-free period (first PD, -1.97 years; 95% CI -3.81 to -0.13), but not with a shorter stroke-free period (fifth PD, -1.21 years; 95% CI -3.11 to 0.68) than never use. Given the observational nature of this study, the possibility of uncontrolled confounding cannot be excluded. Further, immortal time bias, also related to the observational design, cannot be ruled out.CONCLUSIONS: When initiated early in relation to menopause onset, HT was not associated with increased risk of incident stroke, regardless of the route of administration, type of HT, active ingredient, and duration. Generally, these findings held also for haemorrhagic stroke. Our results suggest that the initiation of HT 0-5 years after menopause onset, as compared to never use, is associated with a decreased risk of stroke and haemorrhagic stroke. Late initiation was associated with elevated risks of stroke and haemorrhagic stroke when conjugated equine oestrogen was used as single therapy. Late initiation of combined HT was associated with haemorrhagic stroke risk.
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  • Carroll, Christopher, et al. (författare)
  • Hypoxia Generated by Avian Embryo Growth Induces the HIF-α Response and Critical Vascularization
  • 2021
  • Ingår i: Frontiers in Ecology and Evolution. - : Frontiers Media SA. - 2296-701X. ; 9, s. 1-15
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer research has transformed our view on cellular mechanisms for oxygen sensing. It has been documented that these mechanisms are important for maintaining animal tissues and life in environments where oxygen (O2) concentrations fluctuate. In adult animals, oxygen sensing is governed by the Hypoxia Inducible Factors (HIFs) that are stabilized at low oxygen concentrations (hypoxia). However, the importance of hypoxia itself during development and for the onset of HIF-driven oxygen sensing remains poorly explored. Cellular responses to hypoxia associates with cell immaturity (stemness) and proper tissue and organ development. During mammalian development, the initial uterine environment is hypoxic. The oxygenation status during avian embryogenesis is more complex since O2 continuously equilibrates across the porous eggshell. Here, we investigate HIF dynamics and use microelectrodes to determine O2 concentrations within the egg and the embryo during the first four days of development. To determine the increased O2 consumption rates, we also obtain the O2 transport coefficient (DO2) of eggshell and associated inner and outer shell membranes, both directly (using microelectrodes in ovo for the first time) and indirectly (using water evaporation at 37.5°C for the first time). Our results demonstrate a distinct hypoxic phase (<5% O2) between day 1 and 2, concurring with the onset of HIF-α expression. This phase of hypoxia is demonstrably necessary for proper vascularization and survival. Our indirectly determined DO2 values are about 30% higher than those determined directly. A comparison with previously reported values indicates that this discrepancy may be real, reflecting that water vapor and O2 may be transported through the eggshell at different rates. Based on our obtained DO2 values, we demonstrate that increased O2 consumption of the growing embryo appears to generate the phase of hypoxia, which is also facilitated by the initially small gas cell and low membrane permeability. We infer that the phase of in ovo hypoxia facilitates correct avian development. These results support the view that hypoxic conditions, in which the animal clade evolved, remain functionally important during animal development. The study highlights that insights from the cancer field pertaining to the cellular capacities by which both somatic and cancer cells register and respond to fluctuations in O2 concentrations can broadly inform our exploration of animal development and success.
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  • Casimir, Justin, et al. (författare)
  • Skiftning av åkermark för ett effektivare jordbruk
  • 2019
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Antalet gårdar i Sverige minskar medan deras storlek ökar för att kunna hålla verksamheten konkurrenskraftig på marknaden. En vanlig situation är att gården vill expandera snabbare än det finns tillgänglig mark nära gårdscentrum. Detta leder till att gården får längre avstånd till sin åkermark. Detta extra avstånd har en kostnad, både för gårdens lönsamhet och för miljön.En föregående pilotstudie studerade kostnaden för transport av skörd och stallgödsel (spannmål, vall och stallgödsel). Studien visade att kostnader för transporter blir minst halverad om man byter till mark som ligger närmare gården. Denna studie studerade endast fyra gårdar, och inkluderade inte sociala aspekter.Detta fortsättningsprojekt syftar till att få en bättre insikt i de tekniska (geografiska) och även sociala faktorer kopplade till markbyte. Den tekniska delen av projektet innebär utveckling av ett verktyg för att 1) räkna avstånd mellan gårdscentrum och fält i hela Sverige, 2) identifiera bästa matchningar för markbyte mellan gårdar, och därmed minimera avstånd mellan gårdscentrum och fält, och 3) uppskatta potentiella besparingar av drivmedel och kostnader kopplade till markbyte.Våra resultat visar att verktyget ger ett stabilt underlag som beslutstöd. Däremot behövs mer studier för att komma överens om det bästa sättet att implementera verktyget i Sverige, särskilt angående ägarskap, affärsmodell och utveckling av nya funktioner. Den teoretiska potentialen för markbyte mellan två gårdar är uppskattad till 12,4 %.Den sociala delen av projektet undersökte lantbrukares attityder till markbyte. I semi-strukturerade intervjuer med lantbrukare, och seminarium med andra intressenter, undersökte vi hinder, förutsättningar, samt potential för implementering av verktyget. Våra resultat visar att verktyget var positivt mottaget men att det finns fler faktorer att ta hänsyn till t.ex. jordart, odlingsmetod och förtroende.
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21.
  • Chi, Celestine N., 1978-, et al. (författare)
  • Biophysical Characterization of the Complex between Human Papillomavirus E6 Protein and Synapse-associated Protein 97
  • 2011
  • Ingår i: Journal of Biological Chemistry. - : The American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 286:5, s. 3597-3606
  • Tidskriftsartikel (refereegranskat)abstract
    • The E6 protein of human papillomavirus (HPV) exhibits complex interaction patterns with several host proteins, and their roles in HPV-mediated oncogenesis have proved challenging to study. Here we use several biophysical techniques to explore the binding of E6 to the three PDZ domains of the tumor suppressor protein synapse-associated protein 97 (SAP97). All of the potential binding sites in SAP97 bind E6 with micromolar affinity. The dissociation rate constants govern the different affinities of HPV16 and HPV18 E6 for SAP97. Unexpectedly, binding is not mutually exclusive, and all three PDZ domains can simultaneously bind E6. Intriguingly, this quaternary complex has the same apparent hydrodynamic volume as the unliganded PDZ region, suggesting that a conformational change occurs in the PDZ region upon binding, a conclusion supported by kinetic experiments. Using NMR, we discovered a new mode of interaction between E6 and PDZ: a subset of residues distal to the canonical binding pocket in the PDZ(2) domain exhibited noncanonical interactions with the E6 protein. This is consistent with a larger proportion of the protein surface defining binding specificity, as compared with that reported previously.
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22.
  • Chi, Celestine N., et al. (författare)
  • Conformational change and non-canonical interactions in the complex between human papillomavirus E6 protein and Synapse-Associated Protein 97
  • Tidskriftsartikel (refereegranskat)abstract
    • The E6 protein of human papillomavirus exhibits complex interaction patterns with several host proteins and their roles in HPV mediated oncogensis have proved challenging to study. Here we use several biophysical techniques to explore the binding of E6 to the three PDZ domains of the tumor suppressor protein SAP97. All potential binding sites in SAP97 can bind E6 with low micromolar affinity. Unexpectedly,binding is not mutually exclusive and all three PDZ domains can simultaneously bind E6. Intriguingly, the quaternary complex has the same apparent hydrodynamic volume as the unliganded PDZ region, despite having a doubled mass, suggesting that a conformational change occurs in the PDZ region upon E6 binding. Further, using NMR, we discovered a new mode of interaction between E6 and PDZ, as a subset of residues distal to the binding pocket in the PDZ2 domain was found to exhibit non-canonical interactions with the E6 protein suggesting that a large proportion of the proteins surface defines binding specificity
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23.
  • Chi, Celestine N., et al. (författare)
  • Interactions outside the Boundaries of the Canonical Binding Groove of a PDZ Domain Influence Ligand Binding
  • 2012
  • Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 51:44, s. 8971-8979
  • Tidskriftsartikel (refereegranskat)abstract
    • The postsynaptic density protein-95/discs large/zonula occludens-1 (PDZ) domain is a protein-protein interaction module with a shallow binding groove where protein ligands bind. However, interactions that are not part of this canonical binding groove are likely to modulate peptide binding. We have investigated such interactions beyond the binding groove for PDZ3 from PSD-95 and a peptide derived from the C-terminus of the natural ligand CRIPT. We found via nuclear magnetic resonance experiments that up to eight residues of the peptide ligand interact with the PDZ domain, showing that the interaction surface extends far outside of the binding groove as defined by the crystal structure. PDZ3 contains an extra structural element, a C-terminal helix (α3), which is known to affect affinity. Deletion of this helix resulted in the loss of several intermolecular nuclear Overhauser enhancements from peptide residues outside of the binding pocket, suggesting that α3 forms part of the extra binding surface in wild-type PDZ3. Site-directed mutagenesis, isothermal titration calorimetry, and fluorescence intensity experiments confirmed the importance of both α3 and the N-terminal part of the peptide for the affinity. Our data suggest a general mechanism in which different binding surfaces outside of the PDZ binding groove could provide sites for specific interactions.
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24.
  • Dam, Veerle, et al. (författare)
  • Association of menopausal characteristics and risk of coronary heart disease : A pan-European case-cohort analysis
  • 2019
  • Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:4, s. 1275-1285
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Earlier age at menopause has been associated with increased risk of coronary heart disease (CHD), but the shape of association and role of established cardiovascular risk factors remain unclear. Therefore, we examined the associations between menopausal characteristics and CHD risk; the shape of the association between age at menopause and CHD risk; and the extent to which these associations are explained by established cardiovascular risk factors.Methods: We used data from EPIC-CVD, a case-cohort study, which includes data from 23 centres from 10 European countries. We included only women, of whom 10 880 comprise the randomly selected sub-cohort, supplemented with 4522 cases outside the sub-cohort. We conducted Prentice-weighted Cox proportional hazards regressions with age as the underlying time scale, stratified by country and adjusted for relevant confounders.Results: After confounder and intermediate adjustment, post-menopausal women were not at higher CHD risk compared with pre-menopausal women. Among post-menopausal women, earlier menopause was linearly associated with higher CHD risk [HRconfounder and intermediate adjusted per-year decrease = 1.02, 95% confidence interval (CI) = 1.01-1.03, p = 0.001]. Women with a surgical menopause were at higher risk of CHD compared with those with natural menopause (HRconfounder-adjusted = 1.25, 95% CI = 1.10-1.42, p < 0.001), but this attenuated after additional adjustment for age at menopause and intermediates (HR = 1.12, 95% CI = 0.96-1.29, p = 0.15). A proportion of the association was explained by cardiovascular risk factors.Conclusions: Earlier and surgical menopause were associated with higher CHD risk. These associations could partially be explained by differences in conventional cardiovascular risk factors. These women might benefit from close monitoring of cardiovascular risk factors and disease.
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25.
  • Dybjer, E., et al. (författare)
  • Incretin hormones, insulin, glucagon and advanced glycation end products in relation to cognitive function in older people with and without diabetes, a population-based study
  • 2020
  • Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 37:7, s. 1157-1166
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim The aim of this observational study was to investigate relationships between physiological levels of glucometabolic biomarkers and cognitive test results in a population-based setting. Methods Cross-sectional data were obtained from the Swedish population-based Malmo Diet and Cancer Study Re-examination 2007-2012 comprising 3001 older people (mean age 72 years). Through oral glucose tolerance testing (OGTT), fasting and post-load levels of serum insulin, plasma glucagon, serum glucose-dependent insulinotropic peptide (GIP) and plasma glucagon-like peptide-1 (GLP-1) were measured. Insulin resistance and insulin sensitivity levels were calculated. In 454 participants, advanced glycation end products (AGEs) were estimated through skin autofluorescence. Associations between biomarkers and two cognitive tests, the Mini-Mental State Examination (MMSE) and A Quick Test of Cognitive Speed (AQT) respectively, were explored in multiple regression analyses. Results Positive associations following adjustments for known prognostic factors were found between MMSE scores and insulin sensitivity (B = 0.822, P = 0.004), 2-h plasma glucagon (B = 0.596, P = 0.026), 2-h serum GIP (B = 0.581, P = 0.040) and 2-h plasma GLP-1 (B = 0.585, P = 0.038), whereas negative associations were found between MMSE scores and insulin resistance (B = -0.734, P = 0.006), fasting plasma GLP-1 (B = -0.544, P = 0.033) and AGEs (B = -1.459, P = 0.030) were found. Conclusions Higher levels of insulin sensitivity, GIP and GLP-1 were associated with better cognitive outcomes, but AGEs were associated with worse outcomes, supporting evidence from preclinical studies. Glucagon was linked to better outcomes, which could possibly reflect neuroprotective properties similar to the related biomarker GLP-1 which has similar intracellular properties. Longitudinal and interventional studies are needed to further evaluate neuromodulating effects of these biomarkers. presented at the European Association for the Study of Diabetes (EASD) 2019, Barcelona, Spain
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26.
  • Ekblom Bak, Elin, 1981-, et al. (författare)
  • Accelerometer derived physical activity and subclinical coronary and carotid atherosclerosis : cross-sectional analyses in 22 703 middle-aged men and women in the SCAPIS study
  • 2023
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:11
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The aim included investigation of the associations between sedentary (SED), low-intensity physical activity (LIPA), moderate-to-vigorous intensity PA (MVPA) and the prevalence of subclinical atherosclerosis in both coronaries and carotids and the estimated difference in prevalence by theoretical reallocation of time in different PA behaviours.DESIGN: Cross-sectional.SETTING: Multisite study at university hospitals.PARTICIPANTS: A total of 22 670 participants without cardiovascular disease (51% women, 57.4 years, SD 4.3) from the population-based Swedish CArdioPulmonary bioImage study were included. SED, LIPA and MVPA were assessed by hip-worn accelerometer.PRIMARY AND SECONDARY OUTCOMES: Any and significant subclinical coronary atherosclerosis (CA), Coronary Artery Calcium Score (CACS) and carotid atherosclerosis (CarA) were derived from imaging data from coronary CT angiography and carotid ultrasound.RESULTS: High daily SED (>70% ≈10.5 hours/day) associated with a higher OR 1.44 (95% CI 1.09 to 1.91), for significant CA, and with lower OR 0.77 (95% CI 0.63 to 0.95), for significant CarA. High LIPA (>55% ≈8 hours/day) associated with lower OR for significant CA 0.70 (95% CI 0.51 to 0.96), and CACS, 0.71 (95% CI 0.51 to 0.97), but with higher OR for CarA 1.41 (95% CI 1.12 to 1.76). MVPA above reference level, >2% ≈20 min/day, associated with lower OR for significant CA (OR range 0.61-0.67), CACS (OR range 0.71-0.75) and CarA (OR range 0.72-0.79). Theoretical replacement of 30 min of SED into an equal amount of MVPA associated with lower OR for significant CA, especially in participants with high SED 0.84 (95% CI 0.76 to 0.96) or low MVPA 0.51 (0.36 to 0.73).CONCLUSIONS: MVPA was associated with a lower risk for significant atherosclerosis in both coronaries and carotids, while the association varied in strength and direction for SED and LIPA, respectively. If causal, clinical implications include avoiding high levels of daily SED and low levels of MVPA to reduce the risk of developing significant subclinical atherosclerosis.
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27.
  • Engström, Anna-Lena, et al. (författare)
  • Juvenile arthritis and development of symptoms of temporomandibular disorders: a 15-year prospective cohort study.
  • 2007
  • Ingår i: Journal of orofacial pain. - 1064-6655 .- 1945-3396. ; 21:2, s. 120-6
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: To compare the development of symptoms of temporomandibular disorders (TMD) in a sample of patients with juvenile arthritis (JA) and a matched control sample. METHODS: In 1986, 40 patients with JA (28 girls and 12 boys; mean age +/- SD, 18 +/- 4.5 years) and an age- and sex-matched control sample were examined for signs and symptoms of TMD. Fifteen years later in 2001, a questionnaire concerning symptoms of TMD was sent to these subjects. Twenty-eight individuals (68%) in the JA sample (20 women and 8 men; mean age +/- SD, 35 +/- 5.2 years) and 26 controls (19 women and 7 men; 34 +/- 4.0 years) were available for the follow-up. RESULTS: The overall prevalence of symptoms of TMD increased between the 2 examinations in both groups. The prevalence of reported TMD symptoms, such as jaw pain, fatigue in the jaws, and difficulty opening the jaws wide, as well as awareness of tooth clenching, headaches, neck and shoulder pains, was significantly greater among the JA sample than among the controls at the follow-up. CONCLUSION: The study indicates that prevalence of pain and dysfunction in the craniofacial or cervical regions of JA patients is increased more than 20 years after the onset of JA compared to healthy individuals.
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28.
  • Engström, A., et al. (författare)
  • Polytopes from subgraph statistics
  • 2011
  • Ingår i: FPSAC - Int. Conf. Form. Power Ser. Algebraic Comb.. ; , s. 305-316
  • Konferensbidrag (refereegranskat)abstract
    • We study polytopes that are convex hulls of vectors of subgraph densities. Many graph theoretical questions can be expressed in terms of these polytopes, and statisticians use them to understand exponential random graph models. Relations among their Ehrhart polynomials are described, their duals are applied to certify that polynomials are nonnegative, and we find some of their faces. For the general picture we inscribe cyclic polytopes in them and calculate volumes. From the volume calculations we conjecture that a variation of the Selberg integral indexed by Schur polynomials has a combinatorial formula. We inscribe polynomially parametrized sets, called curvy zonotopes, in the polytopes and show that they approximate the polytopes arbitrarily close. 
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29.
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30.
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31.
  • Engström, Gunnar, et al. (författare)
  • Distribution and determinants of ischaemic heart disease in an urban population. A study from the myocardial infarction register in Malmo, Sweden
  • 2000
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 247:5, s. 588-596
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Age adjusted incidence of myocardial infarction has been found to vary substantially between the residential areas of the city of Malmo. The objective of this study was to assess the extent to which major biological risk factors and socio-economic circumstances account for the differences in incidence of and mortality from myocardial infarction. DESIGN: Ecological study of risk factor prevalence and incidence and mortality from myocardial infarction. SETTING: Seventeen administrative areas in Malmo, Sweden. SUBJECTS: Assessment of risk factor prevalence was based on 28 466 men and women, ranging from 45 to 73 years old, who were recruited as participants in the Malmo Diet and Cancer study. Information on serum lipids was available in a random subsample of 5362 subjects. Information about socio-economic level of the residential area was based on statistics from the Malmo City Council and Statistics Sweden. MAIN OUTCOME MEASURES: Weighted least square regressions between prevalence of risk factors (i.e. smoking, hypertension, obesity, diabetes, hypercholesterolemia and hypertriglyceridemia), a myocardial infarction risk score, a socio-economic score and incidence and mortality from myocardial infarction. RESULTS: The risk factor prevalence and myocardial infarction incidence was highest in areas with low socio-economic level. Prevalence of smoking, obesity and hypertension was significantly associated with myocardial infarction incidence and mortality rates amongst men (all r > 0.60). Prevalence of smoking was significantly associated with incidence and mortality from myocardial infarction amongst women (r = 0.66 and r = 0.61, respectively). A myocardial infarction risk score based on four biological risk factors explained 40-60% of the intra-urban geographical variation in myocardial infarction incidence and mortality. The socio-economic score added a further 2-16% to the explained variance. CONCLUSION: In an urban population with similar access to medical care, well-known biological cardiovascular risk factors account for a substantial proportion of the intra-urban geographical variation of incidence of and mortality from myocardial infarction. The socio-economic circumstances further contribute to the intra-urban variation in disease.
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32.
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33.
  • Engström, Gunnar, et al. (författare)
  • Incidence of myocardial infarction in women. A cohort study of risk factors and modifiers of effect
  • 2000
  • Ingår i: Journal of Epidemiology and Community Health. - 1470-2738. ; 54:2, s. 104-107
  • Tidskriftsartikel (refereegranskat)abstract
    • STUDY OBJECTIVE: To assess whether the increased incidence of myocardial infarction and death associated with smoking, hypertension, hyperlipidaemia and diabetes varies significantly between groups defined in terms of occupation, education and marital status. SETTING: Malmo, Sweden. PARTICIPANTS: 9351 women, aged 28-55, with a mean follow up of 10.7 years. MAIN RESULTS: Smoking, hypertension (> or = 160/95 mm Hg or treatment), hyperlipidaemia (cholesterol > or = 6.5 mmol/l or triglycerides > or = 2.3 mmol/l), diabetes, low occupation and education levels were significantly more common among women who experienced a fatal or nonfatal myocardial infarction during the follow up (n = 104) than in other women (n = 9247). Exposure to smoking, hypertension and hyperlipidaemia showed substantial differences between groups defined in terms of education, occupation and marital status. The association between low occupation and myocardial infarction remained statistically significant after adjustments for several potential confounders (RR = 2.6, 95% CI 1.1, 6.0). Single women had similarly higher adjusted mortality rates than married women (RR = 1.4, 95% CI 1.1, 1.8). When other major risk factors were taken into account, the relative risk for mortality and myocardial infarction associated with smoking was 2.6 (95% CI 2.0, 3.4) and 7.8 (95% CI 4.4, 13.9), respectively. CONCLUSION: In this urban female population, short education and low occupation level were both associated with an increased prevalence of smoking, hypertension, hyperlipidaemia and diabetes. Low occupation level increases the rate of cardiac events caused by exposure to these four risk factors.
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34.
  • Engström, Gunnar, et al. (författare)
  • Inflammation-sensitive plasma proteins and incidence of myocardial infarction in men with low cardiovascular risk.
  • 2003
  • Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 23:12, s. 2247-2251
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective— Myocardial infarction (MI) is sometimes experienced by individuals without any traditional risk factor. This prospective study explored whether incidence of MI in nonsmoking, nondiabetic men with normal blood pressure and serum lipids is related to inflammation-sensitive plasma proteins (ISPs). Methods and Results— Five ISPs ({alpha}1-antitrypsin, haptoglobin, ceruloplasmin, fibrinogen, orosomucoid) were analyzed in 6075 men, 47±3.6 years old. A low-risk group (no traditional risk factor, n=1108) and a high-risk group (>=2 major risk factors, n=1011) were defined. Incidence of MI (n=227) was monitored over 18.1±4.3 years of follow-up. In the low-risk group, the age-adjusted relative risks (RRs) were 1.00 (reference), 1.9 (95% CI, 0.8 to 4.2), 1.8 (95% CI, 0.6 to 5.4), and 2.9 (95% CI, 1.05 to 8.1), respectively, for men with 0, 1, 2 and >=3 ISPs in the top quartile (trend: P=0.03). In this group, the increased risk was observed only after >=10 years of follow-up. In the high-risk group, the age-adjusted RRs were 1.00, 1.4 (95% CI, 0.9 to 2.2), 1.9 (95% CI, 1.2 to 3.1), and 2.0 (95% CI, 1.3 to 3.1), respectively, for men with 0, 1, 2, and >=3 ISPs in the top quartile (trend: P=0.0004). Conclusion— Incidence of MI in nonsmoking, nondiabetic men with normal blood pressure and lipids was related to ISPs. The causes for this relationship remain to be explored.
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35.
  • Engström, Gunnar, et al. (författare)
  • Inflammation-sensitive plasma proteins are associated with increased incidence of heart failure: A population-based cohort study.
  • 2009
  • Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 202, s. 617-622
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Although inflammation has been associated with different cardiovascular diseases, the relationships with future heart failure (HF) are unclear. This population-based study explored whether elevated plasma levels of inflammatory proteins are associated with incidence of HF. METHODS: Five inflammation-sensitive plasma proteins (ISPs, fibrinogen, ceruloplasmin, haptoglobin, orosomucoid, and alpha1-antitrypsin) was measured in 6071 men (mean age 46 years) without history of myocardial infarction (MI) or stroke. Incidence of hospitalizations due to HF (primary diagnosis) was monitored over 22 years of follow-up, in relation to the number of elevated ISPs (i.e., in the 4th quartile). Subjects with myocardial infarction during follow-up were censored. RESULTS: During the follow-up, 159 men were hospitalized due to HF. Baseline levels of all ISPs, except for haptoglobin, were significantly higher in men who developed HF. After adjustments for confounding factors, the hazard ratios (HR) of HF were 1.00 (reference), 1.7 (95% CI: 1.1-2.7), 2.0 (CI: 1.2-3.3) and 2.6 (CI: 1.6-4.1), respectively, in men with none, one, two and three or more ISPs in the 4th quartile (trend: p<0.001). Of the individual ISPs, fibrinogen, ceruloplasmin and alpha1-antitrypsin showed significant relationships with incidence of HF after adjustment for risk factors. CONCLUSION: Plasma levels of inflammatory markers are associated with long-term incidence of hospitalizations due to HF in middle-aged men.
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36.
  • Engström, Gunnar, et al. (författare)
  • Trends in long-term survival after myocardial infarction: less favourable patterns for patients from deprived areas
  • 2000
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 248:5, s. 425-434
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: New treatments have improved the prognosis for patients with acute myocardial infarction. However, studies on long-term survival are not unequivocally in favour of an improved long-term prognosis. This study aimed to analyse trends in 3-year survival in relation to sex, age and socioeconomic level of residential area. SETTING: The Malmo myocardial infarction register, Sweden. PARTICIPANTS: All men and women in the city who, between 1978 and 1995, were admitted for a first acute myocardial infarction (n = 11 226). MAIN OUTCOME MEASURES: Age-standardized 3-year survival rates. RESULTS: Both 28-day and 3-year survival rates improved markedly during the study period. Age-standardized 3-year survival (per 100 patients) amongst men and women who survived 28 days increased, between 1978-81 and 1991-95, from 64 to 78 in men and from 66 to 77 in women, an annual increase of 1.4% (95% CI = 1.1-1.7) and 1.2% (0.8-1.5), respectively. There were marked differences in survival between residential areas with different socioeconomic circumstances. The 3-year survival rates amongst men correlated significantly with the socioeconomic circumstances in the areas expressed in terms of a socioeconomic score (men: r = 0.60, n = 17, P = 0.01; women: r = 0.37, P = 0.15). Trends tended to be less favourable in deprived areas. CONCLUSION: Three-year survival after first myocardial infarction has continuously improved for men and women in all age groups. Prognosis was worse and trends tended to be less favourable for patients from deprived areas.
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37.
  • Engström, Henrik, 1968-, et al. (författare)
  • Prototyping Tools for Game Writers
  • 2018
  • Ingår i: The Computer Games Journal. - : Springer. - 2052-773X. ; 7:3, s. 153-172
  • Tidskriftsartikel (refereegranskat)abstract
    • A game is best evaluated by playing it and prototyping is therefore an important activity in game development. Game writers and narrative designers are responsible for the narrative structure of a game, which may have a varying degree of interactivity to it. The aim of this paper is to analyse the role of prototyping tools for game writers. There is a limited range of such tools available, of which Twine is one of the most established. Most of these tools have a text-based programming interface for modelling of game mechanics. This paper presents Deig—a proto- typing tool for creating point-and-click adventure games. In Deig, game mechanics is modelled graphically using nodes from a set of primitives. We present an interview study where game writing students reflect on their experience of using Deig and Twine as prototyping tools. The result shows that both tools have their merits and complement each other. Deig was found to be intuitive for modelling of game mechanics, which lead students to create interactive narratives. Twine was found to be more useful for experimental writing. The conclusion of this work is that there is a need for a diverse set of prototyping tools to support game writing.
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38.
  • Engström, Jonas, et al. (författare)
  • Characterization of carbon nanotube doped carbon fiber prepreg laminate
  • 2012
  • Ingår i: Proceedings of the 15th European Conference on Composite Materials. - Venice : European Conference on Composite Materials, ECCM. - 9788888785332
  • Konferensbidrag (refereegranskat)abstract
    • The current paper reports results from a preliminary study on PREGCYL™ NC R2HM-01 which is a carbon nanotube doped prepreg produced by Nanocyl. The work consisted of sample manufacturing in autoclave, microcopy analysis with XHR-SEM and mechanical testing. The mechanical testing consisted of tensile tests of unidirectional (in longitudinal direction) and cross-ply laminates. Test of unidirectional laminates showed that stiffness of the PREGCYL material is slightly higher than that of MTM55 composites (111GPa vs 102GPa). The results from tests of cross-ply laminates indicated that damage (transverse cracks) initiation is delayed in PREGCYL composites compare to the MTM55 material. Damage accumulation also seems to be slower in nano-doped composites.
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39.
  • Engström, Patrik, et al. (författare)
  • A 2-Pyridone-Amide Inhibitor Targets the Glucose Metabolism Pathway of Chlamydia trachomatis
  • 2015
  • Ingår i: mBio. - 2161-2129 .- 2150-7511. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • In a screen for compounds that inhibit infectivity of the obligate intracellular pathogen Chlamydia trachomatis, we identified the 2-pyridone amide KSK120. A fluorescent KSK120 analogue was synthesized and observed to be associated with the C. trachomatis surface, suggesting that its target is bacterial. We isolated KSK120-resistant strains and determined that several resistance mutations are in genes that affect the uptake and use of glucose-6-phosphate (G-6P). Consistent with an effect on G-6P metabolism, treatment with KSK120 blocked glycogen accumulation. Interestingly, KSK120 did not affect Escherichia coli or the host cell. Thus, 2-pyridone amides may represent a class of drugs that can specifically inhibit C. trachomatis infection. IMPORTANCE Chlamydia trachomatis is a bacterial pathogen of humans that causes a common sexually transmitted disease as well as eye infections. It grows only inside cells of its host organism, within a parasitophorous vacuole termed the inclusion. Little is known, however, about what bacterial components and processes are important for C. trachomatis cellular infectivity. Here, by using a visual screen for compounds that affect bacterial distribution within the chlamydial inclusion, we identified the inhibitor KSK120. As hypothesized, the altered bacterial distribution induced by KSK120 correlated with a block in C. trachomatis infectivity. Our data suggest that the compound targets the glucose-6-phosphate (G-6P) metabolism pathway of C. trachomatis, supporting previous indications that G-6P metabolism is critical for C. trachomatis infectivity. Thus, KSK120 may be a useful tool to study chlamydial glucose metabolism and has the potential to be used in the treatment of C. trachomatis infections.
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40.
  • Engström, Patrik, 1982-, et al. (författare)
  • A comparative study of RNA and DNA as internal gene expression controls early in the developmental cycle of Chlamydia pneumoniae
  • 2010
  • Ingår i: FEMS Immunology and Medical Microbiology. - 0928-8244 .- 1574-695X. ; 58:2, s. 244-253
  • Tidskriftsartikel (refereegranskat)abstract
    • Many microbial pathogens invade and proliferate within host cells and the molecular mechanism underlying this behavior is currently being revealed for several bacterial species. Testing clinically relevant antibacterial compounds and elucidating their effects on gene expression requires adequate controls, especially when studying genetically intractable organisms such as Chlamydia spp., for which various gene fusions cannot be constructed. Until now, relative mRNA levels in Chlamydia have been measured using different internal gene expression controls, including 16S rRNA, mRNAs, and DNA. Here, we compared the advantages and disadvantages of various internal expression controls during the early phase of Chlamydia pneumoniae development. The relative abundance of target mRNAs varied using the different internal control RNAs. This was partly due to variation in the transcript stability of the RNA species. Also, seven out of nine of the analyzed RNAs increased fivefold or more between 2 and 14 h postinfection, while the amount of DNA and number of cells remained essentially unaltered. Our results suggest that RNA should not be used as a gene expression control during the early phase of Chlamydia development, and that intrinsic bacterial DNA is preferable for that purpose because it is stable, abundant, and its relative amount is generally correlated with bacterial numbers.
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41.
  • Engström, Patrik, 1982- (författare)
  • Chemical genetics discloses the importance of heme and glucose metabolism in Chlamydia trachomatis pathogenesis
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Chlamydiae are important human bacterial pathogens with an intracellular life cycle that consists of two distinct bacterial forms, an infectious form (EB) that infects the eukaryotic host cell, and a non-infectious form (RB) that allows intracellular proliferation. To be successful, chlamydiae need to alternate between EB and RB to generate infectious EB’s which are competent to infect new host cells.Chemical genetics is an attractive approach to study bacterial pathogenesis; in principal this approach relies on an inhibitory compound that specifically inhibits a protein of interest. An obstacle in using this approach is target identification, however whole genome sequencing (WGS) of spontaneous mutants resistant to novel inhibitory compounds has significantly extended the utility of chemical genetic approaches by allowing the identification of their target proteins and/or biological pathways.In this thesis, a chemical genetics approach is used, I have found that heme and glucose metabolism of C. trachomatis is specifically important for the transition from the RB form to the infectious EB form. Heme and glucose metabolism are both coupled to energy metabolism, which suggests a common link between the RB-to-EB transitions. In connection with the above findings I have developed strategies that enable the isolation of isogenic C. trachomatis mutant strains. These strategies are based on WGS of spontaneous mutant populations and subsequent genotyping of clonal strains isolated from these mutant populations. Experiments with the mutant strains suggest that the uptake of glucose-6-phosphate (G-6-P) regulates the RB-to-EB transition, representing one of the first examples where genetics has been used to study C. trachomatis pathogenesis. Additional experiments with the mutant strains indicate that G-6-P promotes bacterial growth during metabolic stress.In concert with other findings presented in this thesis, I have fine-tuned methods that could be employed to reveal how novel inhibitory chemical compounds affect chlamydiae. In a broader context, I suggest that C. trachomatis could be used as a model organism to understand how new inhibitory drugs affect other bacterial pathogens.In addition, I observed that C. pneumoniae infections resulted in generalized bone loss in mice and that these mice display a cytokine profile similar to infected bone cells in vitro. Thus, this study indicates that C. pneumoniae potentially can infect bone cells in vivo, resulting in bone loss, alternatively, the inflammatory responses seen in vivo could be the causative factor of the bone loss observed.
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42.
  • Engström, Patrik, et al. (författare)
  • Expansion of the Chlamydia trachomatis inclusion does not require bacterial replication
  • 2015
  • Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1438-4221 .- 1618-0607. ; 305:3, s. 378-382
  • Tidskriftsartikel (refereegranskat)abstract
    • Chlamydia trachomatis replication takes place inside of a host cell, exclusively within a vacuole known as the inclusion. During an infection, the inclusion expands to accommodate the increasing numbers of C. trachomatis. However, whether inclusion expansion requires bacterial replication and/or de novo protein synthesis has not been previously investigated in detail. Therefore, using a chemical biology approach, we herein investigated C. trachomatis inclusion expansion under varying conditions in vitro. Under normal cell culture conditions, inclusion expansion correlated with C trachomatis replication. When bacterial replication was inhibited using KSK120: an inhibitor that targets C. trachomatis glucose metabolism, inclusions expanded even in the absence of bacterial replication. In contrast, when bacterial protein synthesis was inhibited using chloramphenicol, expansion of inclusions was blocked. Together, these data suggest that de novo protein synthesis is necessary, whereas bacterial replication is dispensable for C trachomatis inclusion expansion. (C) 2015 The Authors. Published by Elsevier GmbH.
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43.
  • Engström, Patrik, 1982-, et al. (författare)
  • Mutations in hemG Mediate Resistance to Salicylidene Acylhydrazides, Demonstrating a Novel Link between Protoporphyrinogen Oxidase (HemG) and Chlamydia trachomatis Infectivity
  • 2013
  • Ingår i: Journal of Bacteriology. - Washington DC, USA : American Society for Microbiology. - 0021-9193 .- 1098-5530. ; 195:18, s. 4221-4230
  • Tidskriftsartikel (refereegranskat)abstract
    • Salicylidene acylhydrazides (SAHs) inhibit the type III secretion system (T3S) of Yersinia and other Gram-negative bacteria. In addition, SAHs restrict the growth and development of Chlamydia species. However, since the inhibition of Chlamydia growth by SAH is suppressed by the addition of excess iron and since SAHs have an iron-chelating capacity, their role as specific T3S inhibitors is unclear. We investigated here whether SAHs exhibit a function on C. trachomatis that goes beyond iron chelation. We found that the iron-saturated SAH INP0341 (IS-INP0341) specifically affects C. trachomatis infectivity with reduced generation of infectious elementary body (EB) progeny. Selection and isolation of spontaneous SAH-resistant mutant strains revealed that mutations in hemG suppressed the reduced infectivity caused by IS-INP0341 treatment. Structural modeling of C. trachomatis HemG predicts that the acquired mutations are located in the active site of the enzyme, suggesting that IS-INP0341 inhibits this domain of HemG and that protoporphyrinogen oxidase (HemG) and heme metabolism are important for C. trachomatis infectivity.
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44.
  • Engström, Per, et al. (författare)
  • Vacancy Referrals, Job Search, and the Duration of Unemployment : a Randomized Experiment
  • 2009
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • One goal of the public employment service is to facilitate matching between unemployed job seekers and job vacancies; another goal is to monitor job search so as to bring search efforts among the unemployed in line with search requirements. The referral of job seekers to vacancies is one instrument used for these purposes. We report results from a randomized Swedish experiment where the outcome of referrals is examined. To what extent do unemployed individuals actually apply for the jobs they are referred to? Does information to job seekers about increased monitoring affect the probability of applying and the probability of leaving unemployment? The experiment indicates that a relatively large fraction (one third) of the referrals do not result in job applications. Information about intensified monitoring causes an increase in the probability of job application, especially among young people. However, we find no significant impact on the duration of unemployment.
  •  
45.
  • Engström, Per, et al. (författare)
  • Vacancy Referrals, Job Search, and the Duration of Unemployment : A Randomized Experiment
  • 2012
  • Ingår i: Labour. - : Wiley. - 1121-7081 .- 1467-9914. ; 26:4, s. 419-435
  • Tidskriftsartikel (refereegranskat)abstract
    • One goal of the Public Employment Service is to facilitate matching between unemployed job-seekers and job vacancies; another goal is to monitor job search so as to bring search efforts among the unemployed in line with search requirements. The referral of job-seekers to vacancies is one instrument used for these purposes. We report results from a randomized Swedish experiment where the outcome of referrals is examined. To what extent do unemployed individuals actually apply for the jobs they are referred to? Does information to job-seekers about increased monitoring affect the probability of applying and the probability of leaving unemployment? The experiment indicates that a relatively large fraction (one-third) of the referrals do not result in job applications. Information about intensified monitoring causes an increase in the probability of job application, especially among young people. However, we find no significant impact on the duration of unemployment.
  •  
46.
  • Gerward, Sofia, et al. (författare)
  • Marital status and occupation in relation to short-term case fatality after a first coronary event--a population based cohort.
  • 2010
  • Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Although marital status and low occupation level has been associated with mortality, the relationship with case fatality rates (CFR) after a coronary event (CE) is unclear. This study explored whether incidence of CE and short-term CFR differ between groups defined in terms of marital status and occupation, and if this could be explained by biological and life-style risk factors. METHODS: Population-based cohort study of 33,224 subjects (67% men), aged 27 to 61 years, without history of myocardial infarction, who were enrolled between 1974 and 1992. Incidence of CE, and CFR (death during the first day or within 28 days after CE, including out-of-hospital deaths) was examined over a mean follow-up of 21 years. RESULTS: A total of 3,035 men (6.0 per 1000 person-years) and 507 women (2.4 per 1000) suffered a first CE during follow-up. CFR (during the 1st day) was 29% in men and 23% in women. After risk factor adjustments, unmarried status in men, but not in women, was significantly associated with increased risk of suffering a CE [hazard ratios (HR) 1.10, 95% CI: 0.97-1.24; 1.42: 1.27-1.58 and 1.77: 1.31-2.40 for never married, divorced and widowed, respectively, compared to married]. Unmarried status, in both gender, was also related with an increased CFR (1st day), taking potential confounders into account (odds ratio (OR) 2.14, 95% CI: 1.63-2.81; 1.91: 1.50-2.43 and 1.49: 0.77-2.89 for never married, divorced and widowed, respectively, compared to married men. Corresponding figures for women was 2.32: 0.93-5.81; 1.87: 1.04-3.36 and 2.74: 1.03-7.28. No differences in CFR (1st day) were observed between occupational groups in neither gender. CONCLUSIONS: In this population-based Swedish cohort, short-term CFR was significantly related to unmarried status in men and women. This relationship was not explained by biological-, life-style factors or occupational level.
  •  
47.
  • Gerward, Sofia, et al. (författare)
  • Survival rate 28 days after hospital admission with first myocardial infarction. Inverse relationship with socio-economic circumstances.
  • 2006
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 259:2, s. 164-172
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To study to what extent geographical differences of the mortality from ischaemic heart disease (IHD) can be accounted for by the 28-day case fatality rate (CFR) following first hospital admittance for acute myocardial infarction (MI) and whether the geographical pattern of survival has any relationship with socio-economic circumstances. Design. Register-based surveillance study. Setting. Seventeen residential areas in Malmo, Sweden. Subjects. All 5533 patients were admitted during 1986-1995 for a first acute MI at Malmo University Hospital. Main outcome measures. CFR is based on record linkage with national registers. Area-specific cardiovascular and socio-economic scores (SES) are based on previous cross-sectional studies. Results. In patients below 75 years of age, differences of the 28-day CFR accounted for 20-30% of the geographical variance in mortality from IHD. No corresponding association was found in older age groups. Patients from areas with low SES had the highest CFR, 23.8%. The odds ratios of fatal outcome for patients from areas with median and low SES (versus high SES) were 1.23 (95% CI: 1.01-1.50) and 1.25 (95% CI: 1.03-1.52), respectively (P for trend: 0.060). The strongest correlation was observed in men below 75 years of age (P for trend: 0.007). During the study period there was an improvement of the survival rate for patients from high and medium SES areas but no corresponding change for patients coming from areas having a low SES. Conclusions. In patients below 75 years, geographical differences of the mortality from IHD were related to differences of the 28-day CFR following hospital admittance for a first MI. Rates of survival were inversely related to socio-economic circumstances in the patient's residential area.
  •  
48.
  • Good, James A. D., 1985-, et al. (författare)
  • Thiazolino 2-Pyridone Amide Inhibitors of Chlamydia trachomatis Infectivity
  • 2016
  • Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 59:5, s. 2094-2108
  • Tidskriftsartikel (refereegranskat)abstract
    • The bacterial pathogen Chlamydia trachomatis is a global health burden currently treated with broad-spectrum antibiotics which disrupt commensal bacteria. We recently identified a compound through phenotypic screening that blocked infectivity of this intracellular pathogen without host cell toxicity (compound 1, KSK 120). Herein, we present the optimization of 1 to a class of thiazolino 2-pyridone amides that are highly efficacious (EC50 <= 100 nM) in attenuating infectivity across multiple serovars of C. trachomatis without host cell toxicity. The lead compound 21a exhibits reduced lipophilicity versus 1 and did not affect the growth or viability of representative commensal flora at 50 mu M. In microscopy studies, a highly active fluorescent analogue 37 localized inside the parasitiphorous inclusion, indicative of a specific targeting of bacterial components. In summary, we present a class of small molecules to enable the development of specific treatments for C. trachomatis.
  •  
49.
  • Haq, S Raza, et al. (författare)
  • Side-Chain Interactions Form Late and Cooperatively in the Binding Reaction between Disordered Peptides and PDZ Domains
  • 2012
  • Ingår i: Journal of the American Chemical Society. - : American Chemical Society. - 0002-7863 .- 1520-5126. ; 134:1, s. 599-605
  • Tidskriftsartikel (refereegranskat)abstract
    • Intrinsically disordered proteins are very common and mediate numerous protein-protein and protein-DNA interactions. While it is clear that these interactions are instrumental for the life of the mammalian cell, there is a paucity of data regarding their molecular binding mechanisms. Here we have used short peptides as a model system for intrinsically disordered proteins. Linear free energy relationships based on rate and equilibrium constants for the binding of these peptides to ordered target proteins, PDZ domains, demonstrate that native side-chain interactions form mainly after the rate-limiting barrier for binding and in a cooperative fashion. This finding suggests that these disordered peptides first form a weak encounter complex with non-native interactions. The data do not support the recent notion that the affinities of intrinsically disordered proteins toward their targets are generally governed by their association rate constants. Instead, we observed the opposite for peptide-PDZ interactions, namely, that changes in K-d correlate with changes in k(off).
  •  
50.
  • Hedberg, Magnus, 1981-, et al. (författare)
  • Cerebrovascular accidents after cardiac surgery : an analysis of CT scans in relation to clinical symptoms
  • 2005
  • Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 39:5, s. 299-305
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a link between aortic manipulation, particle embolization, and cerebrovascular accidents (CVA) in cardiac surgery. The present aim was to study hemispheric side differences of CVA. Cardiac-surgery patients with CVA and with computer tomography (CT) performed (n = 77) were analyzed within a total group of 2641 consecutive cases. CT data were reviewed for hemispheric and vascular distribution, and compared with CVA-symptom data of immediate and delayed type. Of the included patients, 66% had positive CT. In the group of 'cardiac-type' operations (e.g., routine clamping and cannulation) and having immediate CVA, right-hemispheric lesions were more frequent than of the contra-lateral side (p = 0.005). Patients with aortic dissections had strong dominance of bilateral findings, which was different from the unilateral pattern of 'cardiac-type' operations (p = 0.001). The middle-cerebral artery territory dominated, and when involved showed a significant (p = 0.022) right-sided distribution. Both CT and clinical symptoms confirmed that CVA after cardiac surgery has a right-hemispheric predominance. These observations may imply that aortic manipulation directs embolic material towards the brachiocephalic trunk.
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