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Sökning: WFRF:(Ekström Ulf)

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1.
  • Mokhtari, Arash, et al. (författare)
  • Effectiveness and Safety of the European Society of Cardiology 0-/1-h Troponin Rule-Out Protocol : The Design of the ESC-TROP Multicenter Implementation Study
  • 2020
  • Ingår i: Cardiology. - : S. Karger AG. - 1421-9751 .- 0008-6312. ; 145:11, s. 685-692
  • Tidskriftsartikel (refereegranskat)abstract
    • Chest pain is one of the most common complaints at the emergency department (ED), and it is commonly the perceived likelihood of acute coronary syndrome (ACS) that drives management. Guidelines from the European Society of Cardiology (ESC) recommend the use of a 0-/1-h high-sensitivity cardiac troponin T (hs-cTnT) protocol to rule out or in ACS, but this is mostly based on observational studies. The aim of the ESC-TROP trial is to determine the safety and effectiveness of the ESC 0-/1-h hs-cTnT protocol when implemented in routine care. Adult chest pain patients at 5 EDs in the Skåne Region, Sweden, are included in the trial. The 0-/1-h hs-cTnT ESC protocol supplemented with clinical assessment and electrocardiography (ECG) is implemented at 3 EDs, and the other 2 EDs act as concurrent controls. Outcomes will be evaluated during the 10 months after the implementation and the corresponding 10 months of the previous year. The 2 co-primary outcomes are (a) acute myocardial infarction (AMI) and all-cause death within 30 days in patients discharged from the ED, and (b) ED length of stay of the same patients. Secondary outcomes include the proportion of chest pain patients discharged from the ED and the number of ruled-out patients undergoing objective testing within 30 days. The ESC-TROP trial will determine the performance and applicability of the 0-/1-h hs-cTnT ESC protocol supplemented with clinical assessment and ECG when implemented in routine ED care. It will provide evidence whether 0-/1-h hs-cTnT testing is safe, effective, and feasible, and whether widespread implementation as recommended by ESC guidelines should be supported.
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2.
  • Alagia, Michele, et al. (författare)
  • Core-shell photoabsorption and photoelectron spectra of gas-phase pentacene : Experiment and theory
  • 2005
  • Ingår i: Journal of chemical physics Online. - : AIP Publishing. - 1089-7690 .- 0021-9606. ; 122:12, s. 124305-
  • Tidskriftsartikel (refereegranskat)abstract
    • The C K-edge photoabsorption and 1s core-level photoemission of pentacene (C22H14) free molecules are experimentally measured, and calculated by self-consistent-field and static-exchange approximation ab initio methods. Six nonequivalent C atoms present in the molecule contribute to the C 1s photoemission spectrum. The complex near-edge structures of the carbon K-edge absorption spectrum present two main groups of discrete transitions between 283 and 288  eV photon energy, due to absorption to * virtual orbitals, and broader structures at higher energy, involving * virtual orbitals. The sharp absorption structures to the * empty orbitals lay well below the thresholds for the C 1s ionizations, caused by strong excitonic and localization effects. We can definitely explain the C K-edge absorption spectrum as due to both final (virtual) and initial (core) orbital effects, mainly involving excitations to the two lowest-unoccupied molecular orbitals of * symmetry, from the six chemically shifted C 1s core orbitals. ©2005 American Institute of Physics
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3.
  • Alagia, M., et al. (författare)
  • Probing the potential energy surface by highresolution x-ray absorption spectroscopy : The umbrella motion of the coreexcited CH3 free radical
  • 2007
  • Ingår i: Physical Review. A. - 1050-2947 .- 1094-1622. ; 76:2, s. 124305-
  • Tidskriftsartikel (refereegranskat)abstract
    • A detailed study of the umbrellalike vibration in inner-shell spectroscopy is presented. The high-resolution x-ray absorption spectrum for the lowest lying core excitation of the CH3 free radical was recorded. High quality potential energy surfaces (PES) for the initial and final states of the transition were calculated as a function of the symmetrical stretching and the umbrella deformation coordinates. The strong anharmonicity along the umbrella coordinate in the double-well region of the PES of the core excited state has a strong effect on the bending vibrational progressions. The excellent agreement between the experiment and theory allows an accurate spectroscopic characterization of the vibrational structure of the electronic transition, and the estimation of the umbrella inversion time of 149  fs.
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5.
  • Axelsson, Mette, et al. (författare)
  • Mat vid diabetes. : En systematisk översikt med utvärdering av effekter samt hälsoekonomiska och etiska aspekter.
  • 2022
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • SlutsatserTyp 1- och typ 2-diabetes Det finns ett samband mellan att äta medelhavskost och lägre risk att dö i förtid oavsett orsak (måttlig tillförlitlighet). Det finns ett samband mellan att äta en större andel2 fibrer eller baljväxter och lägre risk att dö i förtid oavsett orsak (måttlig tillförlitlighet). Det kan även finnas ett samband mellan att äta en större andel nötter och lägre risk att dö i förtid oavsett orsak (låg tillförlitlighet) samt lägre risk att insjukna i hjärt- och kärlsjukdom (låg tillförlitlighet). Det finns ett samband mellan att dricka mer2 kaffe och lägre risk att dö i förtid oavsett orsak och lägre risk att dö i förtid i kranskärlssjukdom (måttlig tillförlitlighet) samt möjligen en lägre risk att dö i förtid i hjärt- och kärlsjukdom (låg tillförlitlighet). Det råder generell brist på studier med lång uppföljningstid som jämför inverkan av olika slags kostråd på överlevnad, diabeteskomplikationer, diabetesremission3, livskvalitet och biverkningar. Tillförlitligheten av befintliga resultat är dessutom mycket låg för de flesta koster, kostbehandlingar, livsmedel och näringsämnen som har utvärderats. Effekter på hälsa och relaterade mått kan i dessa fall inte bedömas.2. Begreppet ”större andel” eller ”mer” avser inte nödvändigtvis att äta eller dricka mer totalt utan att öka mängden av ett visst livsmedel genom att byta ut annan mat eller dryck.Typ 2-diabetes Det kan finnas ett samband mellan att äta en större andel mättat fett och högre risk för att dö i förtid av hjärt- och kärlsjukdom (låg tillförlitlighet). Det kan även finnas ett samband mellan att äta en större andel enkelomättat fett och lägre risk att dö i förtid oavsett orsak (låg tillförlitlighet). En behandling med en initial period av kraftigt minskat energiintag med hjälp av lågenergipulver (VLED) med efterföljande övergång till mat för viktstabilitet jämfört med vanlig kostbehandling har gynnsamma effekter på livskvalitet (enligt EQ-5D), långtidsblodsocker (HbA1c) och vikt upp till 12 månader (måttlig tillförlitlighet)4. Vidare kan metoder där VLED ingår ha gynnsamma effekter på diabetesremission5 och midjeomfång upp till 12 månader (låg tillförlitlighet) och långtidsblodsocker (HbA1c) upp till 24 månader (låg tillförlitlighet). Intensiv livsstilsbehandling därlågfettkost kombineras med fysisk aktivitet och minskat energiintag har gynnsamma effekter jämfört med vanlig kostbehandling på långtidsblodsocker (HbA1c), vikt, kroppsmasseindex (BMI), midjeomfång och vissa blodfetter upp till 12 månader (måttlig tillförlitlighet)3. Viktminskningen kan kvarstå upp till omkring 10 år (låg tillförlitlighet). Behandlingen kan leda till bättre fysisk livskvalitet upp till 8 år (låg tillförlitlighet) medan effektskillnaden i psykisk livskvalitet under samma tid kan vara obefintlig eller försumbar (låg tillförlitlighet). Jämförelsen påvisar ingen förändrad risk att dö i förtid oavsett orsak eller att dö eller insjukna av kardiovaskulära orsaker efter omkring 10 år (låg tillförlitlighet). I det hälsoekonomiska perspektivet är intensiv livsstilsbehandling mer resurskrävande än vanlig kostbehandling, och beräkningar visar små eller inga vinster i kvalitetsjusterade levnadsår (QALYs) på individnivå. Energirestriktion i samband med intensiv livsstilsbehandling med ketogen kost eller med högproteinkost (20 E%) i kombination med fysisk aktivitet jämfört med vanlig kostbehandling kan ge en viktminskning upp till 11 månader (låg tillförlitlighet) men det saknas studier som kan visa om vikten kan bibehållas på längre sikt. Det saknas studier som undersökt kliniskt viktiga utfall som dödlighet, kardiovaskulära sjukdomar, livskvalitet och diabetesremission.3. Gäller endast vid typ 2-diabetes.4. Utgår från individer med en medelkroppsvikt på cirka 100 kg och medel-HbA1c på 60 mmol/mol.5. Resultaten för utfallet diabetesremission (att uppnå normala blodsockervärden) gäller när en diabetesdiagnos sattes för mindre än 6 år sedan eller för mindre än 3 år sedan. Definitionen för diabetesremission var ett HbA1c på mindre än 48 mmol/mol och att samtidigt vara fri från blodsockersänkande läkemedel.Graviditetsdiabetes Det saknas studier om kost vid graviditetsdiabetes med tillräcklig tillförlitlighet för att kunna bedöma effekterna.
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6.
  • Boren, Jan, et al. (författare)
  • The molecular mechanism for the genetic disorder familial defective apolipoprotein B100
  • 2001
  • Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 276:12, s. 9214-9218
  • Tidskriftsartikel (refereegranskat)abstract
    • Familial defective apolipoprotein B100 (FDB) is a genetic disorder in which low density lipoproteins (LDL) bind defectively to the LDL receptor, resulting in hypercholesterolemia and premature atherosclerosis. FDB is caused by a mutation (R3500Q) that changes the conformation of apolipoprotein (apo) B100 near the receptor-binding site. We previously showed that arginine, not simply a positive charge, at residue 3500 is essential for normal receptor binding and that the carboxyl terminus of apoB100 is necessary for mutations affecting arginine 3500 to disrupt LDL receptor binding. Thus, normal receptor binding involves an interaction between arginine 3500 and tryptophan 4369 in the carboxyl tail of apoB100. W4369Y LDL and R3500Q LDL isolated from transgenic mice had identically defective LDL binding and a higher affinity for the monoclonal antibody MB47, which has an epitope flanking residue 3500. We conclude that arginine 3500 interacts with tryptophan 4369 and facilitates the conformation of apoB100 required for normal receptor binding of LDL. From our findings, we developed a model that explains how the carboxyl terminus of apoB100 interacts with the backbone of apoB100 that enwraps the LDL particle. Our model also explains how all known ligand-defective mutations in apoB100, including a newly discovered R3480W mutation in apoB100, cause defective receptor binding.
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7.
  • Buskqvist, Ulf, 1975- (författare)
  • Medborgarnas röster : studier av Internet som politisk offentlighet
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The Voices of the Citizens: Studies of the Internet as Political Public Sphere. The purpose of the study is to investigate the conditions for and forms of citizen participation in the websites’ communicative practices. A mainpoint is to compare websites located within separate institutional contexts, in terms of how they are designed and how they are used. Three types of websites are studied: media corporations, political parties and social movements, in connection with the Swedish parliamentary election 2002 and the election to the European parliament 2004. The dissertation involves case studies that take into account three different links of the communicative chain: production, content and interaction. The production dimension was studied with the help of qualitative interviews and observation. The content dimension – the design of websites, discourses and communicative invitations – was studied with critical multimodal discourse analysis (see e.g. Kress & van Leeuwen 2001). Finally, the interaction dimension was studied with inspiration from the theoretical and methodological perspectives of discourse and conversation analysis (see e.g. Hutchby 2001, van Dijk 1998, and Fairclough 1995). The results of the case studies of the three categories of websites shows that it is necessary that answers to the question of the Web’s importance for the public sphere be based on concrete empirical studies and an institutional perspective. The studies have shown that websites set up within the frame of media corporations and political parties strive to spread ready-made messages, and partly or entirely avoid interaction with the websites’ visitors. It is a question of activities that display and make visible, but neither open up nor include. On the political youth associations’ and one the social movements’ websites the imagined user is also constructed as a politically interested citizen who wishes to discuss politics with other (youths) in the website’s community, but also as a potential new member of the association.The dissertation emphasis the web as an important complement to the mass-media dominated public arenas and serves the needs of citizens in areas where journalism and established politics do not suffice.
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9.
  • Cappelli, Chiara, et al. (författare)
  • The molecular electric quadrupole moment and electric field gradient induced birefringence (Buckingham effect) of Cl2
  • 2004
  • Ingår i: Journal of Computational Methods in Sciences and Engineering. - 1472-7978 .- 1875-8983. ; 4:3, s. 365-380
  • Tidskriftsartikel (refereegranskat)abstract
    • An ab initio investigation of the molecular properties rationalizing the electric-field-gradient induced birefringence (Buckingham effect) for Cl_2 is presented. The quadrupole moment is determined using hierarchies of basis sets and wavefunction models. The electric dipole polarizability, the dipole - dipole - quadrupole and dipole - dipole - magnetic dipole hyperpolarizabilities are determined exploiting a Coupled Cluster Singles and Doubles (CCSD) response approach. The properties are zero-point vibrationally averaged, and the contribution of excited ro-vibrational states accounted for. To this end, the interatomic ^1Σ_g^+ ground state potential has been computed at CCSD plus perturbative triples - CCSD(T) - level employing a large augmented correlation consistent basis set. The effect of relativity is estimated at the Dirac-Hartree-Fock level. Our best value for the quadrupole moment of Cl_2 is (2.327 ± 0.010) au and it is in excellent agreement with experiment which, after revision and dependent on the procedure employed for correcting the original estimate of (2.24 ± 0.04) au of Graham et al., [Mol. Phys., 93, 49, (1998)], ranges from (2.31 ± 0.04) au to (2.36 ± 0.04) au.
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10.
  • Ekelund, Mats, et al. (författare)
  • Effects of total parenteral nutrition on lipid metabolism in rats
  • 1994
  • Ingår i: JPEN. - : Wiley. - 0148-6071. ; 18:6, s. 503-509
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The pathophysiologic mechanisms behind the development of liver steatosis during total parenteral nutrition (TPN) and the possible relationship to alterations of lipoprotein lipase activities in different tissues are not fully known. It is also unknown whether continuous and discontinuous administration of TPN affect lipid metabolism differently. METHODS: TPN, including 8.4 g of triglycerides per kilogram per day, was given for 10 days to two groups of male Sprague-Dawley rats that received the infusions discontinuously and continuously, respectively. Freely fed rats were used as controls. RESULTS: TPN led to hyperlipidemia and accumulation of triglycerides in the liver. High-density lipoproteins were enriched in triglycerides, whereas high-density lipoprotein cholesterol and phospholipid levels were low. The activities of hepatic lipase were markedly decreased, and lipoprotein lipase activities in adipose tissue and in cardiac muscle were both up-regulated. The increased levels of cholesterol and phospholipids in the serum of TPN animals were more pronounced after discontinuous administration. CONCLUSIONS: TPN including lipids interferes with the normal regulation of lipid metabolism. Although the mechanisms remain obscure, the elevation of lipoprotein lipase activities seems functionally important to accommodate the increased input of triglycerides during TPN. Possibly, the observed alterations in lipase activities may be attributed to a state of hypothyroidism.
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11.
  • Eksandh, Louise, et al. (författare)
  • Different clinical expressions in two families with Stargardt's macular dystrophy (STGD1)
  • 2001
  • Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907. ; 79:5, s. 524-530
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To describe the clinical expressions, with emphasis on electrophysiological examinations, in two Swedish families with Stargardt's macular dystrophy (STGD1). Methods. Two pairs of siblings with STGD1, for whom diagnosis had been confirmed by genetic linkage to the ABCA4 gene region, were examined regarding visual acuity, kinetic perimetry, fundus photography, full-field ERG and multifocal ERG (MERG). Possible disease-causing mutations were screened for by DNA sequencing of selected regions of the ABCA4 gene. Results. All STGD1 patients, had visual acuity 0.07-0.1. The two families presented different fundus appearances, MERGs and implicit times on. 30 Hz flicker white light full-field ERGs. Genetic analysis revealed one unique sequence variation in exon 19 of the ABCA4 gene, in one allele from the patients of one of the families. This point mutation causes the amino acid substitution T972N in the ABCR protein. Conclusion. Two pairs of siblings with STGD1 presented two different expressions of the disease regarding the distribution of the retinal dysfunction. One possible molecular explanation to the different clinical expressions may be the T972N substitution present in the ABCR protein in one of the STGD1 families investigated.
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12.
  • Ekström, Madeleine, 1984- (författare)
  • Oxidation and corrosion fatigue aspects of cast exhaust manifolds
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Emission regulations for heavy-duty diesel engines are becoming increasingly restrictive to limit the environmental impacts of exhaust gases and particles. Increasing the specific power output of diesel engines would improve fuel efficiency and greatly reduce emissions, but these changes could lead to increased exhaust gas temperature, increasing demands on the exhaust manifold material. This is currently the ferritic ductile cast iron alloy SiMo51, containing about 4 wt% Si and ~1 wt% Mo, which operates close to its fatigue and oxidation resistance limits at peak temperature (750C). To ensure high durability at higher temperatures, three different approaches to improving the life of exhaust manifolds were developed in this thesis.The first approach was to modify SiMo51 by adding different combinations of Cr and Ni to improve its high-temperature strength and oxidation resistance, or by applying a thermal barrier coating (TBC) to reduce the material temperature and thereby improve fatigue life. In the second approach, new materials for engine components, e.g. austenitic ductile iron and cast stainless steel, were investigated for their high-temperature fatigue and oxidation properties. In order to identify the most suitable alloys for this application, in the third the environmental effects of the corrosive diesel exhaust gas on the fatigue life of SiMo51 were investigated.The high-temperature oxidation resistance of SiMo51 at 700 and 800C in air was found to be improved by adding Cr, whereas Ni showed adverse effects. The effects of solid-solution hardening from Ni and precipitation hardening from Cr were low at 700C, with improvements only at lower temperatures. Applying a TBC system, providing thermal protection from a ceramic topcoat and oxidation protection from a metallic bond coat, resulted in only small reductions in material temperature, but according to finite element calculations still effectively improved the fatigue life of a turbo manifold. Possible alternative materials to SiMo51 identified were austenitic cast ductile iron Ni-resistant D5S and austenitic cast stainless steel HK30, which provided high durability of exhaust manifolds up to 800 and 900C, respectively. Corrosion fatigue testing of SiMo51 at 700C in diesel exhaust gas demonstrated that the corrosive gas reduced fatigue life by 30-50% compared with air and by 60-75% compared with an inert environment. The reduced fatigue life was associated with a mechanism whereby the crack tip oxidized, followed by crack growth. Thus another potential benefit of TBC systems is that the bond coat may reduce oxidation interactions and further improve fatigue life.These results can be used for selecting materials for exhaust applications. They also reveal many new research questions for future studies. Combining the different approaches of alloy modification, new material testing and improving the performance using coatings widened the scope of how component life in exhaust manifolds can be improved. Moreover, the findings on environmental interactions on SiMo51 fatigue provide a completely new understanding of these processes in ductile irons, important knowledge when designing components exposed to corrosive environments. The novel facility developed for high-temperature corrosion fatigue testing can be useful to other researchers working in this field. 
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13.
  • Ekström, Magnus Pär, et al. (författare)
  • The association of body mass index, weight gain and central obesity with activity-related breathlessness : the Swedish Cardiopulmonary Bioimage Study
  • 2019
  • Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 74:10, s. 958-964
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m(2)) is rapidly increasing globally and its impact on breathlessness is unclear.Methods: This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score >= 1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex.Results: We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m(2); and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness.Conclusion: Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.
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14.
  • Ekström, Sandra, et al. (författare)
  • Dietary intake and plasma concentrations of PUFAs in childhood and adolescence in relation to asthma and lung function up to adulthood
  • 2022
  • Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press (OUP). - 0002-9165 .- 1938-3207. ; 115:3, s. 886-896
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: PUFAs may influence the risk of asthma; however, long-term prospective studies including objective biomarkers of PUFA intake are lacking.Objectives The objective was to investigate the role of dietary intake and plasma concentrations of n–3 and n–6 (ω-3 and ω-6) PUFAs in childhood and adolescence for the development of asthma and lung function up to young adulthood.Methods: The study included participants from the Swedish prospective birth cohort BAMSE. Dietary intake of PUFAs was calculated from FFQs (n = 1992) and plasma proportions of PUFAs were measured in phospholipids (n = 831). We analyzed the n–3 PUFA α-linolenic acid (ALA; 18:3n–3); the sum of very-long-chain (VLC) n–3 PUFAs: EPA (20:5n–3), DHA (22:6n–3), and docosapentaenoic acid (22:5n–3); and the n–6 PUFAs linoleic acid (LA; 18:2n–6) and arachidonic acid (AA; 20:4n–6). Asthma was assessed by questionnaires at 8, 16, and 24 y and lung function was measured by spirometry at 24 y.Results: A high (≥median) self-reported dietary intake of LA at 8 y and AA at 16 y was associated with increased risk of prevalent asthma at 24 y (OR: 1.41; 95% CI: 1.10, 1.82 and OR: 1.32; 95% CI: 1.02, 1.70, respectively). In contrast, plasma proportions of ALA, ∑VLC n–3 PUFAs, and AA at 8 y, as well as LA at 16 y, were inversely associated with prevalent asthma at 24 y (e.g., OR: 0.55; 95% CI: 0.38, 0.81 for ∑VLC n–3 PUFAs). No consistent associations were observed with lung function.Conclusions: High dietary intake of certain n–6 PUFAs in childhood or adolescence may be associated with increased risk of asthma up to young adulthood, whereas dietary biomarkers of certain n–3 and n–6 PUFAs in plasma may be associated with decreased risk. Thus, the role of diet compared with altered metabolism of PUFAs needs further investigation to improve dietary preventive strategies for asthma.
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15.
  • Ekström, Ulf, et al. (författare)
  • A Swedish family with a mutation in the peripherin/RDS gene (Arg-172-Trp) associated with a progressive retinal degeneration
  • 1998
  • Ingår i: Ophthalmic Genetics. - : Swets & Zeitlinger Publishers. - 1744-5094 .- 1381-6810. ; 19:3, s. 149-156
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To clinically characterize a Swedish family with autosomal dominant retinitis pigmentosa due to a mutation, Arg-172-Trp, in the peripherin/RDS gene. METHODS: Full clinical evaluation including kinetic visual field testing, measurement of dark-adaptation threshold, and full-field electroretinography in seven patients with autosomal dominant retinitis pigmentosa and three healthy family members. Denaturing gradient gel electrophoresis (DGGE) was used for mutation screening in seven patients and six healthy members of the family. RESULTS: Three of four siblings from the middle generation and four of the younger generation were heterozygous for the peripherin /RDS Arg-172-Trp mutation. The mutation segregated with the disease. Visual acuity decreased progressively with age and visual fields were moderately constricted in young patients, while central scotoma and constriction of the fields were detected in the family members above 50 years of age. The results from full-field electrography were comparable with a widespread retinal degeneration. CONCLUSIONS: Earlier, the peripherin/RDS Arg-172-Trp mutation was associated primarily with a macular degeneration phenotype. One previous study indicated that this mutation also can give rise to a degeneration of the more peripheral parts of the retina. In the present study, a widespread retinal degeneration is seen in the patients above 50 years of age, carrying the Arg-172-Trp mutation.
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16.
  • Ekström, Ulf, et al. (författare)
  • An efficient screening procedure detecting six novel mutations in the LDL receptor gene in Swedish children with hypercholesterolemia
  • 1995
  • Ingår i: Human Genetics. - 1432-1203. ; 96:2, s. 147-150
  • Tidskriftsartikel (refereegranskat)abstract
    • Familial hypercholesterolemia (FH) is an autosomal semi-dominant disorder caused by defects in the low density lipoprotein receptor (LDLR) gene and is a well-documented risk factor for developing cardiovascular disease. The LDLR genes of five Swedish children with FH were examined in this study. Initial mutation screening was performed by denaturing gradient gel electrophoresis (DGGE) with enzymatically amplified exon-sized fragments, each containing a tailing GC-rich requence. The GC-clamped fragments had been synthesized with a restriction site adjacent to the intron-corresponding sequence to allow detachment of the clamps, thereby rendering the fragments suitable for subsequent analysis by single-strand conformation polymorphism (SSCP) analysis of samples from patients with no DGGE-detectable mutations. In addition, all the LDLR genes of the patients were screened for large alterations by restriction fragment length polymorphism analysis. Following this strategy, seven different, potentially disease-causing mutations were detected in the five children with FH. Six of the alterations, five single-base substitutions and one dinucleotide deletion, have not previously been described. DGGE detected six of the mutations and SSCP the seventh.
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17.
  • Ekström, Ulf, et al. (författare)
  • An individual with a healthy phenotype in spite of a pathogenic LDL receptor mutation (C240F)
  • 1999
  • Ingår i: Clinical Genetics. - : Wiley. - 0009-9163. ; 55:5, s. 332-339
  • Tidskriftsartikel (refereegranskat)abstract
    • Familial hypercholesterolemia (FH) is caused by a defect in the function of the low density lipoprotein (LDL) receptor and inherited in an autosomal, codominant way. In this study we present a 13-year-old girl, compound heterozygote for the LDL receptor mutations C240F and Y167X. Fibroblasts from the patient showed very low cholesterol esterification rate, LDL uptake, and degradation compared to normal fibroblasts (< 2%, 8%, and < 2%, respectively). The C240F mutant was expressed in LDL receptor deficient CHOMldlA7 cells. Analysis of cell extracts by immunoblotting demonstrated delayed processing of the mutated LDL receptor, which was accumulated as a precursor protein of normal size. A high molecular weight form of the receptor was also detectable in these cells, which probably reflects cross-linking through the unpaired cysteine residue in the binding domain. Cells expressing the C240F mutant protein were unable to mediate uptake and degradation of LDL. The two siblings of the index case also carried the C240F mutation, but surprisingly one of them (a 17-year-old brother) showed no signs of hypercholesterolemia. This observation is consistent with the view that there may be cholesterol lowering mechanisms that can be activated, perhaps by mutations in known or hitherto unknown genes.
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18.
  • Ekström, Ulf, 1978- (författare)
  • Birefringences and X-ray absorption from relativistic and nonrelativistic quantum chemical methods
  • 2005
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Application of quantum chemical methods for the prediction and interpretation of optical and X-ray experiments have been performed. X-ray absorption and X-ray photo-electron spectroscopy of pentacene in the gas phase has been studied using the static exchange approximation. A generalizat ion of the static exchange approximation, to the relativistic four-component realm is presented and applied to the H2S molecule. This generalization allows for a description of the effects the strong spin-orbit coupling in the core region of atoms. Two types of birefringences, Faraday effect and electric field gradient induced birefringence, a re calculated for small molecules in the gas phase, and the effects of relativity are considered for these nonlinear optical properties.
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19.
  • Ekström, Ulf, et al. (författare)
  • Characterization of the chemisorption of methylsilane on a au(1,1,1) surface from the silicon K- And L-edge spectra : A theoretical study using the four-component static exchange approximation
  • 2007
  • Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 111:37, s. 13846-13850
  • Tidskriftsartikel (refereegranskat)abstract
    • X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure spectra (NEXAFS) of methylsilane, isolated and chemisorbed to a Au(1,1,1) surface, are determined in the fully relativistic four-component static exchange approximation - both the K- and the L-edge of silicon are addressed in this investigation. In the fully chemisorbed structure, three H(Si) atoms have been cleaved off when Si binds in the hollow site of Au forming three Si - Au bonds of normal length. As due to die tri-coordinated chemisorption, the onsets of the K- and L-edge NEXAFS absorption bands occur some 2.0 and 2.5 eV lower in energy, respectively. The spin-orbit splittings in the silicon 2p-shell are not significantly changed due to adsorption. A partly chemisorbed methylsilane with only one H(Si) bond cleaved was also studied, and it is shown that the polarization dependence in the surface spectra contains details that can be used experimentally to identify the surface coordination of silicon. The red-shifts in the XPS silicon 1s (2p) spectra upon surface binding are 0.95 (0.65) and 1.15 (0.83) eV for the mono- and tricoordinated system, respectively.
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20.
  • Ekström, Ulf, et al. (författare)
  • Detection of alterations in all three exons of the peripherin/RDS gene in Swedish patients with retinitis pigmentosa using an efficient DGGE system
  • 1998
  • Ingår i: Molecular Pathology. - 1366-8714. ; 51:5, s. 287-291
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: To develop a sensitive mutation screening procedure suitable for routine analysis of the peripherin/RDS gene, and to estimate the nature and prevalence of peripherin/RDS gene mutations in Swedish patients with autosomal dominant retinitis pigmentosa. METHODS: To make the method as sensitive as possible, as many as eight segments, covering the three exons and the flanking intron sequences of the peripherin/RDS gene, were analysed by denaturing gradient gel electrophoresis. A group of 38 Swedish patients with a clinical diagnosis of autosomal dominant retinitis pigmentosa were screened for mutations in the peripherin/RDS gene. RESULTS: Three point mutations were found in four of the patients and five polymorphisms were defined. One mutation in exon 1, R172W, has been described previously in other ethnic groups as causing a macular degeneration. Another mutation, in exon 2 and causing the substitution F211L, was found in two unrelated patients. A third mutation, resulting in the likely non-pathogenic substitution S289L, as well as a polymorphism not reported previously, was found in exon 3. CONCLUSIONS: The screening procedure described allows detection of mutations in all of the exons, including the polymorphic 5' and 3' ends of the gene, and is therefore suitable for routine screening of peripherin/RDS gene defects in patients with autosomal dominant retinitis pigmentosa. The frequency of mutations found in the Swedish patient group indicates that defects in the peripherin/RDS gene might be a more common cause of autosomal dominant retinitis pigmentosa than was thought previously.
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21.
  • Ekström, Ulf, et al. (författare)
  • Expression of an LDL receptor allele with two different mutations (E256K and I402T)
  • 2000
  • Ingår i: Molecular Pathology. - 1366-8714. ; 53:1, s. 31-36
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: To investigate the disease causing event in patients with familial hypercholesterolaemia, carrying two mutations each, E256K in exon 6 and I402T in exon 9, of the gene encoding the low density lipoprotein (LDL) receptor. It was not known whether the mutations were positioned in cis or trans, or if they were each pathogenic separately or only when present together. METHODS: Polymerase chain reaction, denaturing gradient gel electrophoresis and sequencing were used to characterise the LDL receptor locus of the patients and family members. The different LDL receptor mutants, constructed in vitro by oligonucleotide directed mutagenesis, were expressed in LDL receptor deficient Chinese hamster ovary (CHO1d1A7) cells, to determine the effects of the mutations on LDL receptor function. RESULTS: The two mutations were located on the same allele of the LDL receptor gene. All mutant constructs resulted in the production of a detectable protein in CHO cells. The cells expressing only the I402T mutation, or the combination of I402T and E256K mutations, were seriously affected in mediating uptake and degradation of LDL. Contrary to initial predictions, the cells expressing only the E256K mutation showed essentially the same binding, uptake, and degradation of 125I labelled LDL as cells transfected with normal LDL receptor cDNA. These results suggest that the pathogenic mutation in the patients heterozygous for the E256K/I402T allele is the I402T mutation, and that E256K alone is a rare sequence variation, which does not affect LDL receptor protein function. E256K was not detected either in DNA from a healthy population or in DNA from other hypercholesterolaemic patients studied. CONCLUSIONS: Despite the information available on the structure-function relations between the LDL receptor and LDL receptor like proteins, predictions about the disease causing potential of a mutation are not reliable. These results suggest that the I402T mutation is pathogenic and that the substitution of E256K alone is a rare sequence variation, without a detectable phenotype modulating effect.
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22.
  • Ekström, Ulf, et al. (författare)
  • Four-component Hartree–Fock calculations of magnetic-field induced circular birefringence—Faraday effect—in noble gases and dihalogens
  • 2005
  • Ingår i: The Journal of Chemical Physics. - : AIP Publishing. - 1050-2947 .- 1094-1622 .- 0021-9606 .- 1089-7690. ; 122, s. 074321-
  • Tidskriftsartikel (refereegranskat)abstract
    • Theeffects of relativity on the magnetic-field induced circular birefringence, orFaraday effect, in He, Ne, Ar, Xe, Rn, F2, Cl2,Br2, and I2 have been determined at the four-component Hartree–Focklevel of theory. A measure of the birefringence is givenby the Verdet constant, which is a third-order molecular propertyand thus relates to quadratic response functions. A fully analyticalnonlinear polarization propagator approach is employed. The results are gaugeinvariant as a consequence of the spatial symmetries in themolecular systems. The calculations include electronic as well as vibrationalcontributions to the property. Comparison with experiment is made forHe, Ne, Ar, Xe, and Cl2, and, apart from neon,the theoretical values of the Verdet constant are within 10%of the experimental ones. The inclusion of nonrelativistically spin-forbidden excitationsin the propagator parametrization has significant effects on the dispersionin general, but such effects are in the general caselargely explained by the use of a resonant-divergent propagator theory.In the present work we do, however, observe noticeable relativisticcorrections to the Verdet constant in the off-resonant regions forsystems with light elements (F2 and Cl2), and nonrelativistic resultsfor the Verdet constant of Br2 are in error by25% in the low-frequency region. ©2005 American Institute of Physics.
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23.
  • Ekström, Ulf, et al. (författare)
  • Insufficient mixing of thawed serum samples leading to erroneous results - experience from a field study and use of a correction procedure
  • 2020
  • Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 80:2, s. 99-105
  • Tidskriftsartikel (refereegranskat)abstract
    • Incorrect analysis results that are close to expected might not be recognized in scientific studies or routine patient care. In two field studies we obtained unexpected results in a large number of samples. The present study aimed to identify the source of error in the samples from these studies and to validate a method to obtain correct results. Pre-analytical procedures were scrutinized, giving no indications of inappropriate pre-analytical sample handling in the field or during transport in a tropical climate. Using a new set of samples from volunteers in simulation experiments, we observed the known concentration gradient of analytes sampled in gel as well as plain tubes after freezer storage and thawing. Experiments demonstrated that mixing of samples by vortexing alone was not sufficient to disrupt the gradient formed by freezing and thawing, which appeared to cause the problem encountered when we in field studies analyzed and biobanked large sample sets by robot pipetting. A correction procedure was introduced, in which the obtained value of an analyte was multiplied by a correction factor calculated for each sample using the expected sodium level (140 mmol/L) divided by the measured sodium value. When it was validated on results from the simulation experiments, we repeatedly found that the correction lead to results very close to true values for analytes of different size and charge. Usefulness of the procedure was demonstrated when applied to a large set of field study results.
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24.
  • Ekström, Ulf, et al. (författare)
  • Internalization of cystatin C in human cell lines.
  • 2008
  • Ingår i: The FEBS Journal. - : Wiley. - 1742-464X. ; Aug 9, s. 4571-4582
  • Tidskriftsartikel (refereegranskat)abstract
    • Altered protease activity is considered important for tumour invasion and metastasis, processes in which the cysteine proteases cathepsin B and L are involved. Their natural inhibitor cystatin C is a secreted protein, suggesting that it functions to control extracellular protease activity. Because cystatins added to cell cultures can inhibit polio, herpes simplex and coronavirus replication, which are intracellular processes, the internalization and intracellular regulation of cysteine proteases by cystatin C should be considered. The extension, mechanism and biological importance of this hypothetical process are unknown. We investigated whether internalization of cystatin C occurs in a set of human cell lines. Demonstrated by flow cytometry and confocal microscopy, A-431, MCF-7, MDA-MB-453, MDA-MB-468 and Capan-1 cells internalized fluorophore-conjugated cystatin C when exposed to physiological concentrations (1 mum). During cystatin C incubation, intracellular cystatin C increased after 5 min and accumulated for at least 6 h, reaching four to six times the baseline level. Western blotting showed that the internalized inhibitor was not degraded. It was functionally intact and extracts of cells exposed to cystatin C showed a higher capacity to inhibit papain and cathepsin B than control cells (decrease in enzyme activity of 34% and 37%, respectively). The uptake of labelled cystatin C was inhibited by unlabelled inhibitor, suggesting a specific pathway for the internalization. We conclude that the cysteine protease inhibitor cystatin C is internalized in significant quantities in various cancer cell lines. This is a potentially important physiological phenomenon not previously described for this group of inhibitors.
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25.
  • Ekström, Ulf (författare)
  • Mutation Analysis and Hypercholesterolemia: Studies in FH patients and in healthy middle-aged men with high, low, or increasing cholesterol levels during a six-year follow-up (the CRISS study).
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Our aims were to characterize familial hypercholesterolemia (FH) in a Swedish FH population and to further elucidate the clinical expression and treatment response in relation to genotype. Secondly, we wanted to identify gene variants, which may have impact on cholesterol levels in apparently healthy subjects. In the search for sequence alterations in the large LDL receptor gene we introduced and refined a sensitive screening method, based on denaturing gradient gel electrophoresis (DGGE). In DNA from 25 FH patients (one homozygote), pathogenic mutations were demonstrated in 18 of the 26 FH alleles (69%) expected to be at hand. This result emphasizes the high sensitivity of the screening system. No single genetic defect predominates in Swedish FH patients. Neither were any large deletions within the LDL receptor gene, nor the apo B-3500 allele, encountered. Four patients with the substitution C122X and four W66G carriers showed about equally high S-Cholesterol levels. Although the treatment response was approximately 45% decrease in LDL-Cholesterol for both of the groups, there was a tendency that the dose-response differed between the two groups, which stimulates to further investigations. Some of the found mutations were also investigated in order to describe their pathogenic potential and genotype-phenotype relationship. Cell culture studies demonstrated that the substitutions C240F and I402T are deleterious for LDL receptor function. In contrast, E256K resulted in virtually normal function. To investigate whether increasing cholesterol concentrations during a six-year follow-up could be attributed to genetic variations, selected parts of the LDL receptor and apo B genes were investigated in: (I) men with high serum cholesterol levels at the entry (n=84); (II) men who showed an increase (n=182) and (III) men who had low cholesterol levels throughout the study (n=77). Pathogenic mutations were mainly encountered in group I. The apo B substitution R3500Q and a previously not described apo B substitution (R3480W) were detected. Seven different sequence alterations were found in the LDL receptor gene. The frequencies of StuI(+) and StuI(-) alleles in exon 8 of the LDL receptor gene differed significantly between the groups (p<0.02). The frequency of the StuI(-) allele in group III (allele frequency 0.006) was markedly lower than observed in other populations.
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26.
  • Ekström, Ulf, et al. (författare)
  • Mutations in the low-density lipoprotein receptor gene in Swedish familial hypercholesterolaemia patients: clinical expression and treatment response
  • 1998
  • Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972. ; 28:9, s. 740-747
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Familial hypercholesterolaemia, an autosomal co-dominant disorder caused by defects in the low-density lipoprotein receptor gene, is strongly associated with premature development of cardiovascular disease. METHODS: In this study, we have applied a gene screening method in a population of familial hypercholesterolaemia patients in order to describe the genetic background of the disease in southern Sweden. These patients were studied with the aim of relating the presence of the different mutations to the clinical expression of the disease and to the response to pharmacological treatment. RESULTS: In 16 out of 21 patients, potentially disease-causing low-density lipoprotein receptor gene defects were found, including five not previously described alterations (C240-->F, C122-->stop, C356-->Y, 785insG, 165delG). No defects in apolipoprotein B were found. One group of patients (n = 4) carried the mutation C122-->stop and another group of patients (n = 4) a mutation causing the substitution W66-->G. Patients in the two genotype subgroups were very similar with respect to lipid levels before treatment. CONCLUSION: A tendency towards differential susceptibility to treatment with statins was observed for the patient groups, encouraging further comparative studies of heterozygous FH patients.
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27.
  • Ekström, Ulf, et al. (författare)
  • Phenotypic expression of autosomal dominant retinitis pigmentosa in a Swedish family expressing a Phe-211-Leu variant of peripherin/RDS
  • 1998
  • Ingår i: Ophthalmic Genetics. - : Swets & Zeitlinger Publishers. - 1744-5094 .- 1381-6810. ; 19:1, s. 27-37
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To characterize the clinical phenotype, with emphasis on electrophysiology, of members of a Swedish family with autosomal dominant retinitis pigmentosa due to a novel mutation, F211L, in the peripherin/RDS gene. METHODS: Nine patients with autosomal dominant retinitis pigmentosa and two healthy family members underwent a full clinical evaluation including kinetic visual field testing, measurement of dark adaptation threshold, and full-field electroretinography. Blood samples were collected and DNA analysis was performed using denaturing gradient gel electrophoresis (DGGE). RESULTS: The grandfather, six of seven siblings from the middle generation, and two young boys carried the mutation F211L in the peripherin/RDS gene. The mutation segregated with the clinical presentation of disease. Fundus examination revealed mainly macular atrophy. All assessed parameters of retinal function (visual acuity, dark adaptation threshold, visual fields, and full-field electroretinograms) demonstrated a successive reduction with increasing age. Full-field electroretinograms showed a diminished rod response in all affected individuals and a reduction of the cone b-wave amplitudes with increasing age, indicating retinitis pigmentosa. In the affected family members, the disease seems to progress at a similar rate with increasing age. CONCLUSIONS: The peripherin/RDS gene mutation F211L is associated with a clinical phenotype and includes early loss of rod function and successive reduction of cone function with increasing age, but impressively well-preserved visual acuity and visual fields in young and middle-aged patients and moderately reduced vision in the old patient. Compared to previously described phenotypes segregating with mutations in the peripherin/RDS gene, the present family demonstrates a more benign clinical phenotype, which is concordant within the family.
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28.
  • Ekström, Ulf, et al. (författare)
  • Polarization propagator for X-ray spectra
  • 2006
  • Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114 .- 1050-2947 .- 1094-1622. ; 97:14
  • Tidskriftsartikel (refereegranskat)abstract
    • A polarization propagator for x-ray spectra is outlined and implemented in density functional theory. It rests on a formulation of a resonant-convergent first-order polarization propagator approach which makes it possible to directly calculate the x-ray absorption cross section at a particular frequency without explicitly addressing the excited states. The quality of the predicted x-ray spectrum relates only to the type of density functional applied without any separate treatment of dynamical relaxation effects.
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29.
  • Ekström, Ulf, et al. (författare)
  • Relativistic four-component static-exchange approximation for core-excitation processes in molecules
  • 2006
  • Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - : American Physical Society. - 1050-2947 .- 1094-1622. ; 73:2
  • Tidskriftsartikel (refereegranskat)abstract
    • A generalization of the static-exchange approximation for core-electron spectroscopies to the relativistic four-component realm is presented. The initial state is a Kramers restricted Hartree-Fock state and the final state is formed as the configuration-interaction single excited state, based on the average of configurations for (n-1) electrons in n near-degenerate core orbitals for the reference ionic state. It is demonstrated that the static-exchange Hamiltonian can be made real by considering a set of time-reversal symmetric electron excitation operators. The static-exchange Hamiltonian is constructed at a cost that parallels a single Fock matrix construction in a quaternion framework that fully exploits time-reversal and spatial symmetries for the D2h point group and subgroups. The K - and L -edge absorption spectra of H2 S are used to illustrate the methodology. The calculations adopt the Dirac-Coulomb Hamiltonian, but the theory is open ended toward improvements in the electron-electron interaction operator. It is demonstrated that relativistic effects are substantial for the L -edge spectrum of sulfur, and substantial deviations from the statistical 2:1 spin-orbit splitting of the intensity distribution are found. The average ratio in the mixed region is 1.54 at the present level of theory.
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30.
  • Ekström, Ulf, et al. (författare)
  • The umbrella motion of core-excited CH3 and CD3 methyl radicals
  • 2008
  • Ingår i: Journal of Chemical Physics. - College Park, MD United States : American Institute of Physics (AIP). - 0021-9606 .- 1089-7690. ; 128:4, s. 044302-1-044302-11
  • Tidskriftsartikel (refereegranskat)abstract
    • An accurate experimental and theoretical study of the lowest core excitationof CH3 and CD3 methyl radicals is presented. The complexvibrational structure of the lowest band of the x-ray absorptionspectrum (XAS) is due to the large variation of themolecular geometry, which is planar in the ground state andpyramidal in the core-excited state. The XAS spectra of thetwo radicals were recorded at high resolution and assigned bytheoretical simulations of the spectra, taking into account the couplingof symmetrical stretching and symmetrical bending (umbrellalike) deformations of theradicals. An excellent agreement between experimental and theoretical spectral profilesallowed us to accurately characterize the vibrational structure of theelectronic transition. The similarities, as well as the differences, ofthe peculiar vibrational progression observed for the two radicals areexplained by the strong anharmonicity along the umbrella coordinate andby the isotopic variation, leading to a different probing ofthe double-well potential energy surface of the core excited stateduring the nuclear motion.
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31.
  • Ekström, Ulf, 1978- (författare)
  • Time-dependent molecular properties in the optical and x-ray regions
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Time-dependent molecular properties are important for the experimental characterization of molecular materials. We show how these properties can be calculated, for optical and x-ray frequencies, using novel quantum chemical methods. For xray absorption there are important relativistic effects appearing, due to the high velocity electrons near the atomic nuclei. These effects are treated rigorously within the four-component static exchange approximation. We also show how electron correlation can be taken into account in the calculation of x-ray absorption spectra, in time-dependent density functional theory based on the complex polarization propagator approach. The methods developed have been applied to systems of experimental interest|molecules in the gas phase and adsorbed on metal surfaces. The effects of molecular vibrations have been take into account both within and beyond the harmonic approximation.
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32.
  • Ekström, Ulf, et al. (författare)
  • X-ray absorption spectra from the resonant-convergent first-order polarization propagator approach
  • 2006
  • Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - : American Physical Society. - 1050-2947 .- 1094-1622. ; 74:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The one-photon absorption cross sections of molecular systems have been determined in the high-energy region from the imaginary part of the electric dipole polarizability tensor. In contrast to commonly adopted state-specific methodologies, the complex polarization propagator approach does not require explicit consideration of the excited states and it is open-ended towards multiphoton absorption. It is shown that the electronic relaxation in the core-hole state is well accounted for in the present approach with use of standard density-functional based electronic structure methods. Sample calculations are presented of the K -edge x-ray absorption spectra for H2 O, CO, C4 H4 N, and C6 H6.
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33.
  • Glaser, J., et al. (författare)
  • Preventing kidney injury among sugarcane workers: Promising evidence from enhanced workplace interventions
  • 2020
  • Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 77:8, s. 527-534
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To assess if improvement of working conditions related to heat stress was associated with improved kidney health outcomes among sugarcane harvest workers in Chichigalpa, Nicaragua, a region heavily affected by the epidemic of chronic kidney disease of non-traditional origin. Methods: Based on our findings during the 2017-2018 harvest (harvest 1), recommendations that enhanced the rest schedule and improved access to hydration and shade were given before the 2018-2019 harvest (harvest 2). Actual work conditions during harvest 2 were then observed. Serum creatinine (SCr) was measured before and at end-harvest, and cross-harvest changes in estimated glomerular filtration rate (eGFR) and incident kidney injury (IKI, ie, SCr increase by ≥0.30 mg/dL or ≥1.5 times the baseline value) were compared between harvest 1 and harvest 2 for three jobs with different physical workloads using regression modelling. Workers who left during harvest were contacted at home, to address the healthy worker selection effect. Results: In burned cane cutters, mean cross-harvest eGFR decreased 6 mL/min/1.73 m2 (95% CI 2 to 9 mL/min/1.73 m2) less and IKI was 70% (95% CI 90% to 50%) lower in harvest 2 as compared with harvest 1 data. No such improvements were seen among seed cutters groups with less successful intervention implementation. Conclusion: Kidney injury risk was again elevated in workers with strenuous jobs. The results support further efforts to prevent kidney injury among sugarcane workers, and other heat-stressed workers, by improving access to water, rest and shade. The distinction between design and implementation of such interventions should be recognised. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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34.
  • Hansson, Erik, 1987, et al. (författare)
  • An explorative study of inflammation-related proteins associated with kidney injury in male heat-stressed workers
  • 2023
  • Ingår i: Journal of Thermal Biology. - : Elsevier BV. - 0306-4565. ; 112
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic kidney disease of non-traditional origin (CKDnt) and acute kidney injury (AKI) often affect heat-stressed Mesoamerican manual workers. Inflammation occurs concurrently with AKI in this population, but its role remains unknown. To explore links between inflammation and kidney injury in heat stress, we compared levels of inflammation-related proteins in cutters with and without increasing serum creatinine levels during sugarcane harvest. These sugarcane cutters have previously been identified to be repeatedly exposed to severe heat stress during the five month harvest season. A nested case-control study was conducted among male Nicaraguan sugarcane cutters in a CKDnt hotspot. Cases (n = 30) were defined as having an increase in creatinine of >= 0.3 mg/dL across the five-month harvest. Controls (n = 57) had stable creatinine levels. Ninety-two inflammation-related proteins in serum were measured before and after harvest using Proximity Extension Assays. Mixed linear regression was used to identify differences in protein concentrations between cases and controls before harvest, differential trends during harvest, and association between protein concentrations and the urine kidney injury markers Kidney Injury Molecule (KIM)-1, Monocyte Chemoattractant Protein (MCP)-1 and albumin. One protein, chemokine (C-C motif) ligand 23 (CCL23), was elevated among cases at pre-harvest. Changes in seven inflammation-related proteins (CCL19, CCL23, colony-stimulating factor 1 [CSF1], hepatocyte and fibroblast growth factors [HGF and FGF23], and tumor necrosis factor beta [TNFB] and TNF-related activation -induced cytokine [TRANCE]) were associated with case status and at least two out of three urine kidney injury markers (KIM-1, MCP-1 and albumin). Several of these have been implicated in myofibroblast activation, which likely is an important step in kidney interstitial fibrotic disease such as CKDnt. This study provides an initial exploration of immune system determinants of, and activation during, kidney injury experienced during prolonged heat stress.
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35.
  • Hansson, Erik, et al. (författare)
  • Pathophysiological mechanisms by which heat stress potentially induces kidney inflammation and chronic kidney disease in sugarcane workers
  • 2020
  • Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 12:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Chronic kidney disease of non-traditional origin (CKDnt) is common among Mesoamerican sugarcane workers. Recurrent heat stress and dehydration is a leading hypothesis. Evidence indicate a key role of inflammation. Methods: Starting in sports and heat pathophysiology literature, we develop a theoretical framework of how strenuous work in heat could induce kidney inflammation. We describe the release of pro-inflammatory substances from a leaky gut and/or injured muscle, alone or in combination with tubular fructose and uric acid, aggravation by reduced renal blood flow and increased tubular metabolic demands. Then, we analyze longitudinal data from >800 sugarcane cutters followed across harvest and review the CKDnt literature to assess empirical support of the theoretical framework. Results: Inflammation (CRP elevation and fever) and hyperuricemia was tightly linked to kidney injury. Rehydrating with sugary liquids and NSAID intake increased the risk of kidney injury, whereas electrolyte solution consumption was protective. Hypokalemia and hypomagnesemia were associated with kidney injury. Discussion: Heat stress, muscle injury, reduced renal blood flow and fructose metabolism may induce kidney inflammation, the successful resolution of which may be impaired by daily repeating pro-inflammatory triggers. We outline further descriptive, experimental and intervention studies addressing the factors identified in this study.
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36.
  • Hansson, Erik, 1987, et al. (författare)
  • Point-of-care biomarkers for prediction of kidney function trajectory among sugarcane cutters: a comparative test accuracy study
  • 2022
  • Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 12:11
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Heat-stressed Mesoamerican workers, such as sugarcane cutters, suffer from high rates of chronic kidney disease of non-traditional origin (CKDnt). We aimed to identify easily available early markers of rapid kidney function decline in a population at high risk of CKDnt. DESIGN: The accuracy of different biomarkers measured during harvest for prediction of cross-harvest kidney function decline were assessed in an exploratory study group, and the performance of the most promising biomarker was then assessed in an independent confirmation group. SETTING: Male sugarcane cutters in El Salvador and Nicaragua. PARTICIPANTS: 39 male Salvadoran sugarcane cutters sampled fortnightly at ≤9 occasions before and after work shift during harvest. 371 male Nicaraguan sugarcane cutters were sampled as part of routine monitoring during two harvests. Cutters worked at high physical intensity at wet-bulb globe temperatures mostly above 29°C for 6-8hours per day 6 days a week during the 5-6months harvest season. PRIMARY OUTCOMES: Change in estimated glomerular filtration rate (CKD Epidemiology Collaboration) across the harvest season (ΔeGFRcross-harvest). RESULTS: Dipstick leukocyturia after work shift in the El Salvadoran group was the most promising marker, explaining >25% of ΔeGFRcross-harvest variance at 8/9 occasions during harvest. Leukocyturia was associated with experiencing fever, little or dark urine, cramps, headache, dizziness and abdominal pain in the preceding 2-week period. Decreasing blood haemoglobin (Hb) and eGFR during harvest were also predictive of ΔeGFRcross-harvest. In the Nicaraguan confirmation dataset, those having ≥++ leukocyturia at any sampling during harvest had a 13 mL/min/1.73 m2 (95% CI 10 to 16mL/min/1.73 m2) worse ΔeGFRcross-harvest than those without recorded leukocyturia. CONCLUSION: Leukocyturia and Hb, both measurable with point-of-care methods, may be early indicators for kidney injury and risk for eGFR decline among heat-stressed male workers, thereby facilitating individual-level prevention and research aiming to understand the causes of CKDnt.
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37.
  • Hansson, Erik, et al. (författare)
  • Workload and cross-harvest kidney injury in a Nicaraguan sugarcane worker cohort
  • 2019
  • Ingår i: Occupational and environmental medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 76:11, s. 818-826
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To examine the association between workload and kidney injury in a fieldworker cohort with different levels of physically demanding work over a sugarcane harvest, and to assess whether the existing heat prevention efforts at a leading occupational safety and health programme are sufficient to mitigate kidney injury. METHODS: Biological and questionnaire data were collected before (n=545) and at the end (n=427) of harvest among field support staff (low workload), drip irrigation workers (moderate), seed cutters (high) and burned sugarcane cutters (very high). Dropouts were contacted (87%) and reported the reason for leaving work. Cross-harvest incident kidney injury (IKI) was defined as serum creatinine increase ≥0.30 mg/dL or ≥1.5 times the baseline value, or among dropouts reporting kidney injury leading to leaving work. RESULTS: Mean cross-harvest estimated glomerular filtration rate change was significantly associated with workload, increasing from 0 mL/min/1.73 m2 in the low-moderate category to -5 mL/min/1.73 m2 in the high and -9 mL/min/1.73 m2 in the very high workload group. A similar pattern occurred with IKI, where low-moderate workload had 2% compared with 27% in the very high workload category. A healthy worker selection effect was detected, with 32% of dropouts reporting kidney injury. Fever and C reactive protein elevation were associated with kidney injury. CONCLUSIONS: Workers considered to have the highest workload had more cross-harvest kidney damage than workers with less workload. Work practices preventing heat stress should be strengthened and their role in preventing kidney damage examined further. Future occupational studies on chronic kidney disease of unknown aetiology should account for a healthy worker effect by pursuing those lost to follow-up.
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38.
  • Henriksson, Johan, et al. (författare)
  • On the evaluation of quadratic response functions at the four-component Hartree-Fock level : Nonlinear polarization and two-photon absorption in bromo- and iodobenzene
  • 2006
  • Ingår i: Journal of Chemical Physics. - : American Institute of Physics (AIP). - 0021-9606 .- 1089-7690. ; 124:21
  • Tidskriftsartikel (refereegranskat)abstract
    • The nonlinear polarization and two-photon absorption parameters have been determined for dibromo- and di-iodobenzene in their meta- and ortho-conformations and with relativistic effects accounted for to a varying degree. By exclusion of small component integrals in the calculations of the first-order hyperpolarizability, results within 1% of fully relativistic four-component Hartree-Fock values are obtained at a cost of 8.7 times the corresponding nonrelativistic calculations. It is shown that the nonlinear absorption in bromobenzene (and even more so in iodobenzene) is broad banded due to spin-orbit interactions among the excited states, and nonrelativistic and scalar relativistic calculations are not to be used in this case. © 2006 American Institute of Physics.
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39.
  • Hofmann, Robin, et al. (författare)
  • Oxygen therapy in suspected acute myocardial infarction
  • 2017
  • Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 377:13, s. 1240-1249
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain. METHODS: In this registry-based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air. RESULTS: A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient-air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient-air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P=0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P=0.33). The results were consistent across all predefined subgroups. CONCLUSIONS: Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality. (Funded by the Swedish Heart–Lung Foundation and others; DETO2X-AMI ClinicalTrials.gov number, NCT01787110.)
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40.
  • Holst-Ekström, Måns, et al. (författare)
  • From A Farm to Cow Chapel: Farming and Forestry in Art
  • 2011
  • Ingår i: Agriculture and Forestry in Sweden Since 1900 - geographical and historical studies. - 1402-0386. - 9789186573119 ; No 54, s. 513-530
  • Bokkapitel (refereegranskat)abstract
    • The article is a survey of how farming and forestry is depicted in art in Sweden during the 19th century. The author discusses what is depicted, as well as how and why. A focus question in the article is the relative abscence of farming and forestry as a motif on the Swedish art scene during the period.
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41.
  • Holst-Ekström, Måns, et al. (författare)
  • Från Spadarvet till Kokapell: Jordbruk och skogsbruk i konsten
  • 2011
  • Ingår i: Jordbruk och skogsbruk i Sverige - studier av de areella näringarnas geografi och historia. - 1402-0386. - 9789186573102 ; nr 53, s. 486-502
  • Bokkapitel (refereegranskat)abstract
    • I artikeln görs en översikt över jordbrukets och skogsbrukets närvaro i konsten i Sverige under 1900-talet. Den innehåller också analyser och diskussioner rörande hur, när och varför det agrara motivet är närvarande alternativt frånvarande i konsten under perioden.
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42.
  • Jacobson, S G, et al. (författare)
  • Digenic inheritance of a ROM1 gene mutation with a peripherin/RDS or rhodopsin mutation in families with retinitis pigmentosa
  • 1999
  • Ingår i: Digital Journal of Ophthalmology. - 1542-8958. ; 5:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Two families with retinitis pigmentosa showed inheritance of an Arg-16-His ROM1 gene mutation with either an Arg-13-Trp RDS mutation or an Arg-135-Trp RHO mutation. The phenotypes of double and single heterozygotes were determined to examine the hypothesis that digenic inheritance may increase disease expression. In the family with ROM1 and RDS mutations, single heterozygotes were normal but one double heterozygote showed severe RP. Two other double heterozygotes, however, were normal by clinical and retinal function tests. In the family with ROM1 and RHO mutations, single heterozygotes with the RHO mutation all manifested RP, while a single heterozygote for the ROM1 mutation was normal. Disease severity was comparable in double heterozygotes and single heterozygotes HAVING the RHO mutation. We conclude that the Arg-16-His ROM1 gene mutation is non-pathogenic in the single heterozygous state, and there is no consistent evidence of digenic augmentation of pathogenicity in double heterozygotes carrying the Arg-16-His ROM1 mutation with either the benign Arg-13-Trp RDS mutation or the disease-causing Arg-135-Trp RHO mutation.
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43.
  • Jemt, Erik, et al. (författare)
  • Outcomes in Emergency Department Patients with Dyspnea versus Chest Pain : A Retrospective Consecutive Cohort Study
  • 2022
  • Ingår i: Emergency Medicine International. - : Hindawi Limited. - 2090-2840 .- 2090-2859. ; 2022, s. 1-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Dyspnea and chest pain are major and important causes of contact at the emergency department (ED). Dyspnea is associated with high morbidity and mortality, but data on characteristics and outcomes compared with chest pain in the ED are limited. This was a retrospective cohort study of consecutive patients with contact causes of dyspnea or chest pain at two Swedish EDs from 2010 to 2014. Hospital admittance, ED revisits, and mortality were analyzed using multivariable regression models, adjusted for ED and markers of disease severity (age, sex, centre, Charlson comorbidity index, c-reactive protein, troponin T, and arrival by ambulance). 29,291 patients (mean age 58.3 years; 48.9% women) with dyspnea (n = 8,812) or chest pain (n = 20,479) were included. Dyspnea patients were older than patients with chest pain (64 vs. 56 years, p < 0.001) and had more comorbidity and higher average blood troponin T and c-reactive protein levels. Dyspnea patients also had higher hospitalization rates (48% vs. 30%; adjOR (95% CI) 2.1-2.3), including the intensive care unit (1.4% vs. 0.1%; adjOR 6.9-15.9), and more ED revisits (11% vs. 7%; adjOR 1.2-1.7) in 30 days. Dyspnea patients had five-fold increased mortality compared to those with chest pain; hazard ratio (HR) 5.1 (4.8-5.4), adjusted for markers of disease severity, the mortality was two-fold higher, HR 2.2 (2.0-2.4). Compared with chest pain patients, ED dyspnea patients are older, have more comorbidity, and have worse outcomes in terms of hospitalization, morbidity, and mortality.
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44.
  • Jiemchooroj, Auayporn, et al. (författare)
  • Near-edge x-ray absorption and natural circular dichroism spectra of L-alanine : A theoretical study based on the complex polarization propagator approach
  • 2007
  • Ingår i: Journal of Chemical Physics. - : American Institute of Physics (AIP). - 0021-9606 .- 1089-7690. ; 127:16
  • Tidskriftsartikel (refereegranskat)abstract
    • The complex polarization propagator method [J. Chem. Phys. 123, 194103 (2005)] has been employed in conjunction with density functional theory and gauge-including atomic orbitais in order to determine the near-edge x-ray absorption and natural circular dichroism spectra of L-alanine in its neutral and zwitterionic forms. Results are presented for the K-edges of carbon, nitrogen, and oxygen. In contrast to traditional methods, the proposed approach enables a direct determination of the spectra at an arbitrary frequency instead of focusing on the rotatory strengths for individual electronic transitions. The propagator includes a complete set of nonredundant electron-transfer operators and allows for full core-hole relaxation. The theoretical spectrum at the nitrogen K-edge of the zwitterion compares well with the experimental spectrum. © 2007 American Institute of Physics.
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45.
  • Nielsen, Christel, et al. (författare)
  • Pregnancy-induced changes in serum concentrations of perfluoroalkyl substances and the influence of kidney function
  • 2020
  • Ingår i: Environmental Health: A Global Access Science Source. - : Springer Science and Business Media LLC. - 1476-069X. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Epidemiological associations between maternal concentrations of perfluoroalkyl substances (PFAS) and birth weight are inconsistent. There is concern that studies based on samples collected in late pregnancy may be confounded by kidney function but studies of the relation between pregnancy-induced changes in PFAS and kidney function are lacking. Our aims were to investigate changes in serum concentrations of perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) from early to late pregnancy and to explore relations to changes in glomerular filtration rate (GFR) and glomerular pore size. Methods: We conducted the study in a cohort of 73 pregnancies of normal-weight Swedish women without gestational diabetes and preeclampsia, enrolled 2009-2014. Blood was collected in median weeks 11 and 36, respectively, and analysed PFAS using liquid chromatography-tandem-mass-spectrometry. We estimated GFR based on creatinine and cystatin C and used the ratio eGFRcystatin C/eGFRcreatinine to indicate glomerular pore size. We used Wilcoxon signed-rank test to compare early and late measures and partial Spearman rank correlations to explore relations between changes in PFAS and kidney function. Results: Median concentrations of PFNA, PFOA and PFOS decreased by 15-21% but changes were uncorrelated to changes in kidney function (partial R = - 0.06-0.11). The observed increase in median PFHxS concentration of 69% was likely an artefact of systematic measurement error caused by coeluting endogenous inferences. Conclusions: Serum concentrations of PFNA, PFOA and PFOS decrease during pregnancy but the magnitudes of change are unrelated to parallel changes in eGFR and glomerular pore size, suggesting that changes in these indicators of kidney function are not important confounders in studies of PFAS and birth weight in pregnancies without gestational diabetes and preeclampsia. © 2020 The Author(s).
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46.
  • Roth, Bengt, et al. (författare)
  • Effects of heparin and low molecular weight heparin on lipid transport during parenteral feeding in the rat
  • 1996
  • Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172. ; 40:1, s. 102-111
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Treatment with heparin has been reported to interfere with lipid metabolism by release of Lipoprotein Lipase (LPL) into the circulation. The purpose of the present study was to determine the effects on LPL activity by anticoagulants in combination with total parenteral nutrition (TPN) in the rat. In an earlier investigation we could show that TPN, per se, caused a three-fold increase of triglyceride content in liver tissue, retention of lipids in the circulation and disturbed cholesterol metabolism with accumulation of cholesterol in the non High Density Lipoprotein (HDL) fraction of lipoproteins. The activity of Hepatic Lipase (HL) was decreased, while the activities of LPL in adipose tissue and heart were up-regulated. METHODS: Effects on lipid metabolism by TPN for seven days with or without simultaneous administration of heparin or Low Molecular Weight Heparin (LMWH) were studied in 52 healthy male Sprague-Dawley rats. Combinations of Heparin or LMWH and discontinuous or continuous administration of TPN solutions (including approximately 8 g triglycerides/kg body weight daily) were investigated. RESULTS: Addition of LMWH, but not heparin, to treatment with TPN resulted in significant up-regulation of LPL activity in the heart. Combination of heparin and continuous administration of TPN solutions was followed by modest, but significant, increases of S-Triglycerides and HDL-Triglycerides. No differences between the TPN groups were observed concerning liver steatosis, cholesterol metabolism, phospholipid metabolism or HL activity. CONCLUSION: Treatment with LMWH during TPN resulted in up-regulated LPL activity in the heart, which might represent a compensatory mechanism for enzyme release from the capillary walls induced by anticoagulants. Administration of heparin, a more effective lipase-releasing agent, was not associated with increased LPL activity. Heparin treatment in combination with continuous TPN administration was followed by increased levels of triglycerides in blood and HDL particles, suggesting that treatment with heparin might have impaired the capacity for LPL up-regulation, resulting in the development of hyperlipidemia. Further investigations are necessary for evaluation of the mechanisms. Depletion of LPL activity could not be demonstrated by this study in healthy rats.
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47.
  •  
48.
  • Schlingemann, Joerg, et al. (författare)
  • Novel means of viral antigen identification : Improved detection of avian influenza viruses by proximity ligation
  • 2010
  • Ingår i: Journal of Virological Methods. - : Elsevier BV. - 0166-0934 .- 1879-0984. ; 163:1, s. 116-122
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent outbreaks of avian influenza in different parts of the world have caused major economic losses for the poultry industry, affected wildlife seriously and present a significant threat even to human public health, due to the risk for zoonotic transmission. The ability to recognize avian influenza viruses (AIVs) early is of paramount importance to ensure that appropriate measures can be taken quickly to contain the outbreak. In this study. the performance of a proximity ligation assay (PLA) for the detection of AIV antigens in biological specimens was evaluated. It is shown that PLA: (i) as a novel principle of highly sensitive antigen detection is extending the arsenal of tools for the diagnosis of AIV; (ii) is very specific, nearly as sensitive as a commonly used reference real-time PCR assay, and four orders of magnitude more sensitive than a sandwich ELISA, utilizing the same antibody; (iii) avoids the necessity of nucleic acids extraction, which greatly facilitates high-throughput implementations; (iv) allows the use of inactivated samples, which safety can be transported from the field to diagnostic laboratories for further analysis. In summary, the results demonstrate that PLA is suited for rapid, accurate and early detection of AIV.
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49.
  •  
50.
  • Sterner Isaksson, Sofia, et al. (författare)
  • The effect of carbohydrate intake on glycaemic control in individuals with type 1 diabetes: a randomised, open-label, crossover trial
  • 2024
  • Ingår i: The Lancet Regional Health - Europe. - 2666-7762. ; 37
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Few studies have examined the effects of lower carbohydrate diets on glucose control in persons with type 1 diabetes (T1D). The objective of the study was to investigate whether a moderate carbohydrate diet improves glucose control in persons with T1D. Methods: A randomised, multicentre, open-label, crossover trial over 12 weeks. There were 69 individuals assessed for eligibility, 54 adults with T1D and HbA1c ≥ 58 mmol/mol (7.5%) were randomised. Interventions were moderate carbohydrate diet versus traditional diet (30 vs 50% of total energy from carbohydrates) over four weeks, with a four-week wash-out period between treatments. Masked continuous glucose monitoring was used to evaluate effects on glucose control. The primary endpoint was the difference in mean glucose levels between the last 14 days of each diet phase. Findings: 50 individuals were included in the full analysis set with a mean baseline HbA1c of 69 mmol/mol (8.4%), BMI 29 kg/m2, age of 48 years, and 50% were female. The difference in mean glucose levels between moderate carbohydrate and traditional diet was −0.6 mmol/L, 95% CI −0.9 to −0.3, p < 0.001. Time in range increased during moderate carbohydrate diet by 4.7% (68 min/24 h) (95% CI 1.3 to 8.0), p = 0.008. Time above range (>10 mmol/L) decreased by 5.9% (85 min/24 h), 95% CI −9.6 to −2.2, p = 0.003. There were no significant differences in the standard deviation of glucose levels (95% CI −0.3 to 0.0 mmol/L, p = 0.15) or hypoglycaemia in the range <3.9 mmol/L (95% CI −0.4 to 2.9%, p = 0.13) and <3.0 mmol/L (95% CI −0.4 to 1.6%, p = 0.26). Four participants withdrew, none because of adverse events. There were no serious adverse events including severe hypoglycaemia and ketoacidosis. Mean ketone levels were 0.17 (SD 0.14) mmol/L during traditional and 0.18 (SD 0.13) mmol/L during moderate carbohydrate diet (p = 0.02). Interpretation: A moderate carbohydrate diet is associated with decreases in mean glucose levels and time above range and increases in time in range without increased risk of hypoglycaemia or ketoacidosis compared with a traditional diet in individuals with T1D. Funding: The Healthcare Board, Region Västra Götaland, The Dr P Håkansson Foundation and the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement [ALFGBG-966173].
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