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Sökning: WFRF:(Taube A)

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1.
  • van Bragt, JJMH, et al. (författare)
  • Characteristics and treatment regimens across ERS SHARP severe asthma registries
  • 2020
  • Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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  • Hollo, G, et al. (författare)
  • Referral for first glaucoma surgery in Europe, the ReF-GS study
  • 2019
  • Ingår i: European journal of ophthalmology. - : SAGE Publications. - 1724-6016 .- 1120-6721. ; 29:4, s. 406-416
  • Tidskriftsartikel (refereegranskat)abstract
    • To analyze the appropriateness of referrals for incisional glaucoma-surgery in Europe. Methods: Referrals for the first open-angle glaucoma surgery between January and October 2017 were analyzed in 18 countries: 8 “old” European Union, 7 “new” European Union and 3 non-European Union European countries. Results: Most eyes had primary open-angle or exfoliative glaucoma. The average mean deviation was −13.8 dB with split fixation in 44.3%. No structural progression analysis was made before the referrals. The most common medications were the combination of a prostaglandin analog, timolol and a carbonic anhydrase inhibitor (30.0%), and all other combinations comprising ⩾ 3 molecules (33.8%). Laser trabeculoplasty was reported in only 18.4%. Of the 294 referrals, 41.5% were appropriate and timely, 35.0% appropriate but later than optimal, and 17.6% appropriate but too late (minimal vision maintained). The treatment period was significantly longer (median: 7 years) in the “old” European Union countries than in the other groups (3 and 2 years, respectively). No between-group differences were seen in intraocular pressure and mean deviation, but the non-European Union group referred the patients at significantly lower cup/disk ratio and eye drop usage than the other groups. Split fixation was significantly more common in the “old” (60.6%) than the “new” European Union countries (38.7%), and in both EU country-groups than in the non-European Union countries (13.6%). Conclusions: Of 294 European open-angle glaucoma referrals for first glaucoma-surgery, 41.5% were completely satisfactory. The damage was typically advanced, and the care varied considerably among the countries. This suggests that further efforts are necessary to improve glaucoma care in Europe.
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  • Santoru, A, et al. (författare)
  • A new potassium-based intermediate and its role in the desorption properties of the K-Mg-N-H system.
  • 2016
  • Ingår i: Physical chemistry chemical physics : PCCP. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 18:5, s. 3910-3920
  • Tidskriftsartikel (refereegranskat)abstract
    • New insights into the reaction pathways of different potassium/magnesium amide-hydride based systems are discussed. In situ SR-PXD experiments were for the first time performed in order to reveal the evolution of the phases connected with the hydrogen releasing processes. Evidence of a new K-N-H intermediate is shown and discussed with particular focus on structural modification. Based on these results, a new reaction mechanism of amide-hydride anionic exchange is proposed.
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9.
  • Dongiovanni, P, et al. (författare)
  • Causal relationship of hepatic fat with liver damage and insulin resistance in nonalcoholic fatty liver.
  • 2018
  • Ingår i: Journal of internal medicine. - : Wiley. - 1365-2796 .- 1365-2796 .- 0954-6820. ; 283:4, s. 356-370
  • Tidskriftsartikel (refereegranskat)abstract
    • Nonalcoholic fatty liver disease is epidemiologically associated with hepatic and metabolic disorders. The aim of this study was to examine whether hepatic fat accumulation has a causal role in determining liver damage and insulin resistance.We performed a Mendelian randomization analysis using risk alleles in PNPLA3, TM6SF2, GCKR and MBOAT7, and a polygenic risk score for hepatic fat, as instruments. We evaluated complementary cohorts of at-risk individuals and individuals from the general population: 1515 from the liver biopsy cohort (LBC), 3329 from the Swedish Obese Subjects Study (SOS) and 4570 from the population-based Dallas Heart Study (DHS).Hepatic fat was epidemiologically associated with liver damage, insulin resistance, dyslipidemia and hypertension. The impact of genetic variants on liver damage was proportional to their effect on hepatic fat accumulation. Genetically determined hepatic fat was associated with aminotransferases, and with inflammation, ballooning and fibrosis in the LBC. Furthermore, in the LBC, the causal association between hepatic fat and fibrosis was independent of disease activity, suggesting that a causal effect of long-term liver fat accumulation on liver disease is independent of inflammation. Genetically determined hepatic steatosis was associated with insulin resistance in the LBC and SOS. However, this association was dependent on liver damage severity. Genetically determined hepatic steatosis was associated with liver fibrosis/cirrhosis and with a small increase in risk of type 2 diabetes in publicly available databases.These data suggest that long-term hepatic fat accumulation plays a causal role in the development of chronic liver disease.
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10.
  • Heaney, Liam G., et al. (författare)
  • Eosinophilic and Noneosinophilic Asthma : An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort
  • 2021
  • Ingår i: Chest. - : Elsevier BV. - 0012-3692. ; 160:3, s. 814-830
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. Research Question: What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? Study Design and Methods: This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). Results: One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV1, 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy. Interpretation: According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.
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  • Cavallari, Larisa H., et al. (författare)
  • Association of the GGCX (CAA) 16/17 repeat polymorphism with higher warfarin dose requirements in African Americans
  • 2012
  • Ingår i: Pharmacogenetics & Genomics. - 1744-6872 .- 1744-6880. ; 22:2, s. 152-158
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Little is known about genetic contributors to higher than usual warfarin dose requirements, particularly for African Americans. This study tested the hypothesis that the gamma-glutamyl carboxylase (GGCX) genotype contributes to warfarin dose requirements greater than 7.5 mg/day in an African American population.Methods A total of 338 African Americans on a stable dose of warfarin were enrolled. The GGCX rs10654848 (CAA) n, rs12714145 (G>A), and rs699664 (p.R325Q); VKORC1 c.-1639G>A and rs61162043; and CYP2C9*2, *3, *5, *8, *11, and rs7089580 genotypes were tested for their association with dose requirements greater than 7.5mg/day alone and in the context of other variables known to influence dose variability.Results The GGCX rs10654848 (CAA) 16 or 17 repeat occurred at a frequency of 2.6% in African Americans and was overrepresented among patients requiring greater than 7.5 mg/day versus those who required lower doses (12 vs. 3%, P = 0.003; odds ratio 4.0, 95% confidence interval, 1.5-10.5). The GGCX rs10654848 genotype remained associated with high dose requirements on regression analysis including age, body size, and VKORC1 genotype. On linear regression, the GGCX rs10654848 genotype explained 2% of the overall variability in warfarin dose in African Americans. An examination of the GGCX rs10654848 genotype in warfarin-treated Caucasians revealed a (CAA) 16 repeat frequency of only 0.27% (P = 0.008 compared with African Americans).Conclusion These data support the GGCX rs10654848 genotype as a predictor of higher than usual warfarin doses in African Americans, who have a 10-fold higher frequency of the (CAA) 16/17 repeat compared with Caucasians. Pharmacogenetics and Genomics 22: 152-158 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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  • Kaczmarski, J., et al. (författare)
  • Controlling In-Ga-Zn-O thin films transport properties through density changes
  • 2016
  • Ingår i: Thin Solid Films. - : Elsevier BV. - 0040-6090. ; 608, s. 57-61
  • Tidskriftsartikel (refereegranskat)abstract
    • In the following study we investigate the effect of the magnetron cathode current (I-c) during reactive sputtering of In-Ga-Zn-O (a-IGZO) on thin-films nanostructure and transport properties. All fabricated films are amorphous, according to X-ray diffraction measurements. However, High Resolution Transmission Electron Microscopy revealed the a-IGZO fabricated at I-C = 70 mA to contain randomly-oriented nanocrystals dispersed in amorphous matrix, which disappear in films deposited at higher cathode current. These nanocrystals have the same composition as the amorphous matrix. One can observe that, while I-C is increased from 70 to 150 mA, the carrier mobility improves from mu(Hall) = 6.9 cm(2)/Vs to mu(Hall) = 9.1 cm(2)/Vs. Additionally, the increase of I-C caused a reduction of the depletion region trap states density of the Ru-Si-O/In-Ga-Zn-O Schottky barrier. This enhancement in transport properties is attributed to the greater overlapping of s-orbitals of the film-forming cations caused by increased density, evidenced by X-ray reflectivity, at a fixed chemical composition, regardless nanostructure of thin films. (C) 2016 Elsevier B.V. All rights reserved.
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  • Kaczmarski, J., et al. (författare)
  • Transparent Ru–Si–O/In–Ga–Zn–O MESFETs on flexible polymer substrates
  • 2018
  • Ingår i: IEEE Transactions on Electron Devices. - 1557-9646 .- 0018-9383. ; 65:1, s. 129-135
  • Tidskriftsartikel (refereegranskat)abstract
    • With the development of novel device applications, e.g., in the field of Internet of Things or point-of-care personalized diagnostic systems, came an increased demand for MESFETs for fast and low-power consumption integrated circuits and active-matrix displays. In this paper, we present fabrication and characterization of transparent Ru–Si–O/In–Ga–Zn–O MESFETs on flexible substrates. The use of transparent conducting oxide, namely, Ru–Si–O, as Schottky gate electrode, allows for processing the devices at room temperature, enabling the utilization of such low-temperature substrates as polyethylene terephthalate foil and paper. It was shown that tuning the device geometry allows realization of transistors providing on-current up to 2 mA, while the highest on-to-off current ratio equals 2 × 105, with off-current below 1 nA, carrier mobility in the channel exceeds 9 cm2·V−1·s−1, and subthreshold swing is below 250 mV·decade−1
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  • Liu, Yanhong, et al. (författare)
  • Genomic copy number imbalances associated with bone and non-bone metastasis of early-stage breast cancer
  • 2014
  • Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 143:1, s. 189-201
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study is to identify and validate copy number aberrations in early-stage primary breast tumors associated with bone or non-bone metastasis. Whole-genome molecular inversion probe arrays were used to evaluate copy number imbalances (CNIs) in breast tumors from 960 early-stage patients with information about site of metastasis. The CoxBoost algorithm was used to select metastasis site-related CNIs and to fit a Cox proportional hazards model. Gains at 1q41 and 1q42.12 and losses at 1p13.3, 8p22, and Xp11.3 were significantly associated with bone metastasis. Gains at 2p11.2, 3q21.3-22.2, 3q27.1, 10q23.1, and 14q13.2-3 and loss at 7q21.11 were associated with non-bone metastasis. To examine the joint effect of CNIs and clinical predictors, patients were stratified into three risk groups (low, intermediate, and high) based on the sum of predicted linear hazard ratios. For bone metastasis, the hazard (95 % confidence interval) for the low-risk group was 0.32 (0.11-0.92) compared to the intermediate-risk group and 2.99 (1.74-5.11) for the high-risk group. For non-bone metastasis, the hazard for the low-risk group was 0.34 (0.17-0.66) and 2.33 (1.59-3.43) for the high-risk group. The prognostic value of loss at 8p22 for bone metastasis and gains at 10q23.1 for non-bone metastasis, and gain at 11q13.5 for both bone and non-bone metastases were externally validated in 335 breast tumors pooled from four independent cohorts. Distinct CNIs are independently associated with bone and non-bone metastasis for early-stage breast cancer patients across cohorts. These data warrant consideration for tailoring surveillance and management of metastasis risk.
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  • McKay, Kyla A, et al. (författare)
  • Military service and related risk factors for amyotrophic lateral sclerosis.
  • 2021
  • Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 143:1, s. 39-50
  • Tidskriftsartikel (refereegranskat)abstract
    • The cause of amyotrophic lateral sclerosis (ALS) is unknown, but occupations have been explored as a potential proxy measure of risk. There is a substantial body of literature connecting military service to ALS. We aimed to summarize and assess the quality of this evidence.Systematic review of the literature, including observational studies which explored one of the following exposures: general military service (army, air force, marines, or navy); or specific exposures associated with military service measured amongst military personnel. The outcome of interest was ALS incidence, which could include onset, diagnosis, or death from ALS.A total of 2642 articles were screened. Following exclusion, 19 articles remained for inclusion in the systematic review, including 1 meta-analysis and 18 original observational studies. Most studies were of moderate quality. In general, the relationship between military service was suggestive of an increased risk, particularly among Gulf War and WWII veterans. Exposure to pesticides (including Agent Orange) certain chemicals (exhaust, burning agents), heavy metals, and head trauma, appeared to increase the risk of ALS among military personnel.There is a possible association between military service and the subsequent development of ALS; however, the evidence was limited. Studies were generally hindered by small sample sizes and inadequate follow-up time. Future studies should endeavour to objectively measure specific exposures, or combinations thereof, associated with military service, as this will be of vital importance in implementing preventative strategies into military organisations.
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  • Peterson, Stefan, et al. (författare)
  • Classification of thyroid size by palpation and ultrasonography in field surveys
  • 2000
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 355, s. 106-110
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Goitre surveys are used to assess the degree of iodine deficiency in a population. The change of goitre classification made by WHO in 1994 implied that a smaller thyroid size should be regarded as goitre. Furthermore, the acceptable goitre prevalence was lowered from 10% to 5%, and ultrasonography was recommended as a more precise method for diagnosis of goitre. We studied the effects of the change of palpation system, and compared the precision of the old and new systems with that of ultrasonographic examination. METHODS: We studied 225 schoolchildren (aged 7-14 years) in a highland village in Tanzania. The size of the thyroid was assessed in duplicate by ultrasonography and by WHO's 1960 and 1994 palpation systems. The latter were done by three examiners. Variations within and between examination methods and examiners were assessed, and measurement errors by ultrasonography were assessed from duplicate examinations. The sensitivity and specificity of the two palpation systems were calculated, with diagnosis by ultrasonography as the gold standard. Apparent palpation prevalences were calculated at a "true" 5% prevalence. FINDINGS: The lowered criterion for goitre resulted in an extra 20-33% of children being diagnosed as having goitre by palpation. The variation between repeat examinations was only slightly smaller by ultrasonography (kappa=0.63) than by experienced examiners (kappa=0.57-0.58). The variation between thyroid volume estimation by ultrasonography and the true volume was about 50% due to both measurement error and variation in the shape of thyroid lobes. The new goitre criterion decreased specificity from 76% to 29%, whereas sensitivity rose from 56% to 80%. In contrast, a suggested sharpening of the old criterion increased specificity to 90%. INTERPRETATION: A return to the old (1960) palpation criterion for goitre: "lobes larger than the terminal phalanxes of thumbs" and to an accepted palpation goitre prevalence of 10% can allow affordable monitoring of thyroid size through palpation in field surveys.
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  • Pistidda, C., et al. (författare)
  • Hydrogen storage systems from waste Mg alloys
  • 2014
  • Ingår i: Journal of Power Sources. - : Elsevier BV. - 1873-2755 .- 0378-7753. ; 270, s. 554-563
  • Tidskriftsartikel (refereegranskat)abstract
    • The production cost of materials for hydrogen storage is one of the major issues to be addressed in order to consider them suitable for large scale applications. In the last decades several authors reported on the hydrogen sorption properties of Mg and Mg-based systems. In this work magnesium industrial wastes of AZ91 alloy and Mg-10 wt.% Gd alloy are used for the production of hydrogen storage materials. The hydrogen sorption properties of the alloys were investigated by means of volumetric technique, in situ synchrotron radiation powder X-ray diffraction (SR-PXD) and calorimetric methods. The measured reversible hydrogen storage capacity for the alloys AZ91 and Mg-10 wt.% Gd are 4.2 and 5.8 wt.%, respectively. For the Mg-10 wt.% Gd alloy, the hydrogenated product was also successfully used as starting reactant for the synthesis of Mg(NH2)(2) and as MgH2 substitute in the Reactive Hydride Composite (RHC) 2LiBH(4) + MgH2. The results of this work demonstrate the concrete possibility to use Mg alloy wastes for hydrogen storage purposes. (C) 2014 Elsevier B.V. All rights reserved.
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  • Taube, D., et al. (författare)
  • Generic tacrolimus in solid organ transplantation
  • 2014
  • Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 28:5, s. 623-632
  • Forskningsöversikt (refereegranskat)abstract
    • The availability of a wide range of immunosuppressive therapies has revolutionized the management of patients who have undergone solid organ transplantation (SOT). However, the cost of immunosuppressive drugs remains high. This situation has led to the development of generic equivalents, which are similar in quality, safety, and efficacy to their approved innovator drugs. There are data available for three generic brands, tacrolimus (Intas), tacrolimus (PharOS), and tacrolimus (Sandoz). Bioequivalence has been demonstrated for generic tacrolimus (Sandoz) within a narrow therapeutic range to its innovator tacrolimus drug (Prograf) in both healthy volunteers and kidney transplant patients. Clinical experience with this generic tacrolimus formulation has also been established in both de novo and conversion patients who have undergone kidney and liver transplantation, as well as in conversion of other SOT patients, including lung and heart recipients.
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  • Udugama, Isuru A., et al. (författare)
  • The Role of Big Data in Industrial (Bio)chemical Process Operations
  • 2020
  • Ingår i: Industrial & Engineering Chemistry Research. - : American Chemical Society (ACS). - 0888-5885 .- 1520-5045. ; 59:34, s. 15283-15297
  • Tidskriftsartikel (refereegranskat)abstract
    • With the emergence of Industry 4.0 and Big Data initiatives, there is a renewed interest in leveraging the vast amounts of data collected in (bio)chemical processes to improve their operations. The objective of this article is to provide a perspective of the current status of Big-Data-based process control methodologies and the most effective path to further embed these methodologies in the control of (bio)chemical processes. Therefore, this article provides an overview of operational requirements, the availability and the nature of data, and the role of the control structure hierarchy in (bio)chemical processes and how they constrain this endeavor. The current state of the seemingly competing methodologies of statistical process monitoring and (engineering) process control is examined together with hybrid methodologies that are attempting to combine tools and techniques that belong to either camp. The technical and economic considerations of a deeper integration between the two approaches is then explored, and a path forward is proposed.
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  • Andersson-Assarsson, Johanna C., 1974, et al. (författare)
  • Evolution of age-related mutation-driven clonal haematopoiesis over 20 years is associated with metabolic dysfunction in obesity
  • 2023
  • Ingår i: Ebiomedicine. - 2352-3964. ; 92
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Haematopoietic clones caused by somatic mutations with >= 2% variant allele frequency (VAF) increase with age and are linked to risk of haematological malignancies and cardiovascular disease. Recent observations suggest that smaller clones (VAF<2%) are also associated with adverse outcomes. Our aims were to determine the prevalence of clonal haematopoiesis driven by clones of variable sizes in individuals with obesity treated by usual care or bariatric surgery (a treatment that improves metabolic status), and to examine the expansion of clones in relation to age and metabolic dysregulation over up to 20 years.Methods Clonal haematopoiesis-driver mutations (CHDMs) were identified in blood samples from participants of the Swedish Obese Subjects intervention study. Using an ultrasensitive assay, we analysed single-timepoint samples from 1050 individuals treated by usual care and 841 individuals who had undergone bariatric surgery, and multiple-timepoint samples taken over 20 years from a subset (n = 40) of the individuals treated by usual care.Findings In this explorative study, prevalence of CHDMs was similar in the single-timepoint usual care and bariatric surgery groups (20.6% and 22.5%, respectively, P = 0.330), with VAF ranging from 0.01% to 31.15%. Clone sizes increased with age in individuals with obesity, but not in those who underwent bariatric surgery. In the multiple-timepoint analysis, VAF increased by on average 7% (range -4% to 24%) per year and rate of clone growth was negatively associated with HDL-cholesterol (R = -0.68, 1.74 E-04).Interpretation Low HDL-C was associated with growth of haematopoietic clones in individuals with obesity treated by usual care.
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  • Christakoudi, Sofia, et al. (författare)
  • Development and validation of the first consensus gene-expression signature of operational tolerance in kidney transplantation, incorporating adjustment for immunosuppressive drug therapy
  • 2020
  • Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 58
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Kidney transplant recipients (KTRs) with "operational tolerance" (OT) maintain a functioning graft without immunosuppressive (IS) drugs, thus avoiding treatment complications. Nevertheless, IS drugs can influence gene-expression signatures aiming to identify OT among treated KTRs. Methods: We compared five published signatures of OT in peripheral blood samples from 18 tolerant, 183 stable, and 34 chronic rejector KTRs, using gene-expression levels with and without adjustment for IS drugs and regularised logistic regression. Findings: IS drugs explained up to 50% of the variability in gene-expression and 20-30% of the variability in the probability of OT predicted by signatures without drug adjustment. We present a parsimonious consensus gene-set to identify OT, derived from joint analysis of IS-drug-adjusted expression of five published signature gene-sets. This signature, including CD40, CTLA4, HSD11B1, IGKV4-1, MZB1, NR3C2, and RAB40C genes, showed an area under the curve 0.92 (95% confidence interval 0.88-0.94) in cross-validation and 0.97 (0.93-1.00) in six months follow-up samples. Interpretation: We advocate including adjustment for IS drug therapy in the development stage of gene-expression signatures of OT to reduce the risk of capturing features of treatment, which could be lost following IS drug minimisation or withdrawal. Our signature, however, would require further validation in an independent dataset and a biomarker-led trial. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license. (http://creativecommons.org/licenses/by/4.0/)
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  • Egecioglu, Emil, 1977, et al. (författare)
  • Central NMU signaling in body weight and energy balance regulation: evidence from NMUR2 deletion and chronic central NMU treatment in mice.
  • 2009
  • Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 297:3
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the role of the central neuromedin U (NMU) signaling system in body weight and energy balance regulation, we examined the effects of long-term intracerebroventricular (icv) infusion of NMU in C57Bl/6 mice and in mice lacking the gene encoding NMU receptor 2. In diet-induced obese male and female C57BL/6 mice, icv infusion of NMU (8 microg x day(-1) x mouse(-1)) for 7 days decreased body weight and total energy intake compared with vehicle treatment. However, these parameters were unaffected by NMU treatment in lean male and female C57BL/6 mice fed a standard diet. In addition, female (but not male) NMUR2-null mice had increased body weight and body fat mass when fed a high-fat diet but lacked a clear body weight phenotype when fed a standard diet compared with wild-type littermates. Furthermore, female (but not male) NMUR2-null mice fed a high-fat diet were protected from central NMU-induced body weight loss compared with littermate wild-type mice. Thus, we provide the first evidence that long-term central NMU treatment reduces body weight, food intake, and adiposity and that central NMUR2 signaling is required for these effects in female but not male mice.
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28.
  • Elo, Maria, et al. (författare)
  • Who is doing "transnational diaspora entrepreneurship"? : Understanding formal identity and status
  • 2022
  • Ingår i: Journal of world business (Print). - : Elsevier. - 1090-9516 .- 1878-5573. ; 57:1
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper addresses transnational diaspora entrepreneurship (TDE), its superdiversity and respective formal identity and status. As migration increases, formal identity becomes a panacea for migrants' economic participation and global entrepreneurial policies. Our review of TDE literature identified a lack of specification of TDE types and criteria. We develop a taxonomy and discuss TDE problems addressing formal identity, generation, mixed-origin, multi-location, diversity of migratory patterns and cross-border entrepreneurial business activities. Since policymaking employs formal status for impeding or facilitating cross-border venturing, it is crucial to reduce the ambiguity of terms and categories and facilitate more nuanced and accurate theorizing and policymaking.
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  • Frei, K. M., et al. (författare)
  • A matter of months: High precision migration chronology of a Bronze Age female
  • 2017
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Establishing the age at which prehistoric individuals move away from their childhood residential location holds crucial information about the socio dynamics and mobility patterns in ancient societies. We present a novel combination of strontium isotope analyses performed on the over 3000 year old "Skrydstrup Woman" from Denmark, for whom we compiled a highly detailed month-scale model of her migration timeline. When combined with physical anthropological analyses this timeline can be related to the chronological age at which the residential location changed. We conducted a series of high-resolution strontium isotope analyses of hard and soft human tissues and combined these with anthropological investigations including CT-scanning and 3D visualizations. The Skrydstrup Woman lived during a pan-European period characterized by technical innovation and great social transformations stimulated by long-distance connections; consequently she represents an important part of both Danish and European prehistory. Our multidisciplinary study involves complementary biochemical, biomolecular and microscopy analyses of her scalp hair. Our results reveal that the Skrydstrup Woman was between 17-18 years old when she died, and that she moved from her place of origin -outside present day Denmark- to the Skrydstrup area in Denmark 47 to 42 months before she died. Hence, she was between 13 to 14 years old when she migrated to and resided in the area around Skrydstrup for the rest of her life. From an archaeological standpoint, this one-time and one-way movement of an elite female during the possible "age of marriageability" might suggest that she migrated with the aim of establishing an alliance between chiefdoms. Consequently, this detailed multidisciplinary investigation provides a novel tool to reconstruct high resolution chronology of individual mobility with the perspective of studying complex patterns of social and economic interaction in prehistory.
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32.
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33.
  • Hovland, A, et al. (författare)
  • Om ångestsyndrom
  • 2018
  • Ingår i: Fysisk aktivitet som medicin. - Stockholm : SISU idrottsböcker. - 9789177270355 ; , s. 293-298
  • Bokkapitel (populärvet., debatt m.m.)
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34.
  • Kjellman, Bengt, et al. (författare)
  • Depression
  • 2008
  • Ingår i: FYSS 2008 - Fysisk aktivitet i sjukdomsprevention och sjukdomsbehandling. - : Statens folhälsoinstitut. - 9789172575431 ; , s. 281-291
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • Fysisk aktivitet har positiv effekt vid depression både för att förhindra depressionsepisoder och för att behandla sådana, såväl akut som på längre sikt. Den fysiska träningen sker med fördel parallellt med sedvanlig behandling med mediciner och samtal. Även om många studier har metodologiska brister och att det fortfarande finns få långtidsstudier, har fysisk träning vid lätt och måttlig depression klart vetenskapligt stöd när det gäller akut behandling och som ett medel att minska risken för återfall. En preventiv effekt har konstaterats vid epidemiologiska studier och vid långtidsstudier med uppföljning upp till tio år. Övriga hälsoeffekter av fysisk aktivitet är också viktiga, då depression ofta samvarierar med kroppsliga sjukdomar. Fysisk aktivitet är en stor vinst, både för den enskilda och för samhället.
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35.
  • Koivula, A, et al. (författare)
  • Phakic refractive lens: two-year results
  • 2008
  • Ingår i: Journal of refractive surgery (Thorofare, N.J. : 1995). - 1081-597X. ; 24:5, s. 507-515
  • Tidskriftsartikel (refereegranskat)
  •  
36.
  • Linnakylä, P, et al. (författare)
  • Factors behind Low Reading Literacy Achievement
  • 2004
  • Ingår i: Scandinavian Journal of Educational Research. - : Informa UK Limited. - 0031-3831 .- 1470-1170. ; 48:3, s. 231-249
  • Tidskriftsartikel (refereegranskat)
  •  
37.
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38.
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39.
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40.
  • Martinsen, E, et al. (författare)
  • Om depression
  • 2018
  • Ingår i: Fysisk aktivitet som medicin. - Stockholm : SISU idrottsböcker. - 9789177270355 ; , s. 177-182
  • Bokkapitel (populärvet., debatt m.m.)
  •  
41.
  • Nyström, B., et al. (författare)
  • A small group Whiplash-Associated-Disorders (WAD) patients with central neck pain and movement induced stabbing pain, the painful segment determined by mechanical provocation : Fusion surgery was superior to multimodal rehabilitation in a randomized trial
  • 2016
  • Ingår i: Scandinavian Journal of Pain. - : Elsevier. - 1877-8860 .- 1877-8879. ; 12, s. 33-42
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe majority of patients suffering from a whiplash injury will recover, but some will have symptoms (Whiplash Associated Disorders, WAD) for years despite conservative treatment. Some of these patients perceive neck pain that might come from a motion segment, possibly the disc. In comprehensive reviews no evidence has been found that fusion operations have a positive treatment effect on neck pain in WAD patients.PurposeOur aim was to evaluate the possibility of (a) selecting a subgroup of chronic WAD patients based on specified symptoms possibly indicating segmental pain, and (b) treating said segmental pain through fusion operation based on non-radiological segment localization. The hypothesis was that fusion operation in this selected subgroup of chronic WAD patients could alleviate perceived neck pain.MethodsEligible patients for the study had a traffic accident as the origin for their neck pain, and no previous neck symptoms. Neck pain should be the predominant symptom and the pain origin reported to be in the midline, being dull, aching in character and at sudden movements combined by a stabbing pain in the same area. Forty-nine patients with these specified symptoms were identified among a large number of chronic WAD patients. Those selected had pronounced symptoms for a median of around 50 months and had previously been investigated and fully treated within the ordinary healthcare system without success.No neurological abnormalities were to be found at clinical examination and no specific changes to be seen on X-ray and MRI. The patients were randomized to either cervical fusion operation or multimodal rehabilitation. By using a mechanical provocation test the level/s to be fused were identified. In all but one patient the surgery was performed anteriorly using microsurgical technique and a right-sided Smith-Pedersen approach and plate fixation. The multimodal rehabilitation at the Clinic of Medical Rehabilitation, Karolinska Hospital, Stockholm, included outpatient treatment for four days a week for six weeks and included treatment by physician, physiotherapists, occupational therapist, psychologists, social-service worker and nurses. Perceived change in neck pain was assessed using the Balanced Inventory for Spinal Disorders questionnaire at the 2-year-follow-up.ResultsMean age of the patients was 38 and 40 years (surgery and rehabilitation groups, respectively), the most common type of accident being rear-end collision. At clinical examination muscle tenderness was not an outstanding sign. In most patients the mid-cervical region appeared to be the painful area but one patient localized the pain to C1. At follow-up 67% of the patients in the surgery group and 23% in the rehabilitation group assessed improvements in the ITT analysis. Corresponding proportions in the per protocol analysis were 83% and 12%, respectively.ConclusionsThe results support the supposition that among patients with central neck pain for long periods of time following a whiplash injury there are some in whom the neck pain emanates from a motion segment, probably the disc, a situation suitable for fusion surgery.ImplicationsThorough individual symptom evaluation in patients with chronic WAD may identify patients who will benefit from cervical fusion surgery.
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42.
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43.
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44.
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45.
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46.
  • Sachs, Lisbeth, et al. (författare)
  • Risk in numbers - Difficulties in the transformation of genetic knowledge from research to people - The case of hereditary cancer
  • 2001
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 40:4, s. 445-453
  • Tidskriftsartikel (refereegranskat)abstract
    • Difficulties in communicating diagnostic information are exacerbated when the 'diagnosis' is a 'genetic risk' for cancer. The risk estimation demanded in this situation differs from other types of probability estimations. Observations of participants in 45 consultation sessions between physicians and potential patients were conducted at a clinic for hereditary cancer to explore the communication of genetic information. Thirty-three sessions were audiotaped, transcribed verbatim and analyzed, along with notes from the other sessions. A dominant theme was found to be numerical discussion of risk. Further analysis resulted in the description of problems for practitioners in the process of translating scientific knowledge into clinical management. Problems in providing information include unclear aims of the consultation sessions, mixing various types of background information and probabilities, recognizing how low the predictive values are, and difficulties in communicating the relationship between probability and conclusions. Problems in communicating information about the genetic risk for cancer are of at least two types: dilemmas arising from uncertainties implicit in the nature of the information itself and difficulties in communicating information in a manner that those concerned can interpret. These issues need clarification, so that information with far-reaching consequences can be made as clear and comprehensible as possible for those involved.
  •  
47.
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48.
  • Salomé, Nicolas, et al. (författare)
  • On the central mechanism underlying ghrelin's chronic pro-obesity effects in rats: new insights from studies exploiting a potent ghrelin receptor antagonist.
  • 2009
  • Ingår i: Journal of neuroendocrinology. - : Wiley. - 1365-2826 .- 0953-8194. ; 21:9, s. 777-85
  • Tidskriftsartikel (refereegranskat)abstract
    • In the present study, we explore the central nervous system mechanism underlying the chronic central effects of ghrelin with respect to increasing body weight and body fat. Specifically, using a recently developed ghrelin receptor antagonist, GHS-R1A (JMV2959), we investigate the role of GHS-R1A in mediating the effects of ghrelin on energy balance and on hypothalamic gene expression. As expected, in adult male rats, chronic central treatment with ghrelin for 14 days, when compared to vehicle-treated control rats, resulted in an increased body weight, lean mass and fat mass (assessed by dual X-ray absorptiometry), dissected white fat pad weight, cumulative food intake, food efficiency, respiratory exchange ratio and a decrease of energy expenditure. Co-administration of the ghrelin receptor antagonist JMV2959 suppressed/blocked the majority of these effects, with the notable exception of ghrelin-induced food intake and food efficiency. The hypothesis emerging from these data, namely that GHS-R1A mediates the chronic effects of ghrelin on fat accumulation, at least partly independent of food intake, is discussed in light of the accompanying data regarding the hypothalamic genes coding for peptides and receptors involved in energy balance regulation, which were found to have altered expression in these studies.
  •  
49.
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50.
  • Taube, Fabian, 1967, et al. (författare)
  • Amyotrophic lateral sclerosis (ALS) and environmental risk factors in a military context : Amyotrofisk lateral skleros (ALS) och miljöriskfaktorer inom militär verksamhet
  • 2020
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • In Sweden, approximately 220 people are diagnosed with amyotrophic lateral sclerosis (ALS) yearly. In 90% of the cases, the cause seems to be a combination of mutations and environmental risk factors, such as exposure to chemicals, head trauma, extreme physical exercise and electromagnetic radiation. Studies have found a correlation between elevated levels of lead in blood and increased risk of ALS among US veterans. However, the occurrence of ALS among professional shooters or recreational shooters has not been made clear. There is a small but significant risk increase for ALS in workers with prolonged occupational exposure to pesticides. However, military personnel are not considered to have prolonged exposure of pesticides. There is a slight increase in risk of ALS in workers who are continuously exposed to low frequency electromagnetic radiation. However, it is unclear whether electromagnetic radiation increases the risk of ALS among military personnel. Studies indicate an increase in ALS among persons exposed to hard physical exertion and/or repeated mild trauma. It is possible that this type of exposure may cause the type of improper protein folding associated with the onset of ALS. Military service members are exposed to low-grade, sometimes prolonged and parallel, exposure to several environmental risk factors. It is possible that multifactorial exposures increase the risk of developing ALS.
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