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1.
  • Bergemalm, Daniel, 1977-, et al. (author)
  • Systemic Inflammation in Preclinical Ulcerative Colitis
  • 2021
  • In: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
  • Journal article (peer-reviewed)abstract
    • Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored.Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.
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2.
  • Dupont, Chris L., et al. (author)
  • Functional Tradeoffs Underpin Salinity-Driven Divergence in Microbial Community Composition
  • 2014
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2, s. e89549-
  • Journal article (peer-reviewed)abstract
    • Bacterial community composition and functional potential change subtly across gradients in the surface ocean. In contrast, while there are significant phylogenetic divergences between communities from freshwater and marine habitats, the underlying mechanisms to this phylogenetic structuring yet remain unknown. We hypothesized that the functional potential of natural bacterial communities is linked to this striking divide between microbiomes. To test this hypothesis, metagenomic sequencing of microbial communities along a 1,800 km transect in the Baltic Sea area, encompassing a continuous natural salinity gradient from limnic to fully marine conditions, was explored. Multivariate statistical analyses showed that salinity is the main determinant of dramatic changes in microbial community composition, but also of large scale changes in core metabolic functions of bacteria. Strikingly, genetically and metabolically different pathways for key metabolic processes, such as respiration, biosynthesis of quinones and isoprenoids, glycolysis and osmolyte transport, were differentially abundant at high and low salinities. These shifts in functional capacities were observed at multiple taxonomic levels and within dominant bacterial phyla, while bacteria, such as SAR11, were able to adapt to the entire salinity gradient. We propose that the large differences in central metabolism required at high and low salinities dictate the striking divide between freshwater and marine microbiomes, and that the ability to inhabit different salinity regimes evolved early during bacterial phylogenetic differentiation. These findings significantly advance our understanding of microbial distributions and stress the need to incorporate salinity in future climate change models that predict increased levels of precipitation and a reduction in salinity.
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3.
  • Papakokkinou, Eleni, et al. (author)
  • Prevalence of Nelson's syndrome after bilateral adrenalectomy in patients with cushing's disease: a systematic review and meta-analysis
  • 2021
  • In: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403.
  • Journal article (peer-reviewed)abstract
    • Purpose Bilateral adrenalectomy (BA) still plays an important role in the management of Cushing's disease (CD). Nelson's syndrome (NS) is a severe complication of BA, but conflicting data on its prevalence and predicting factors have been reported. The aim of this study was to determine the prevalence of NS, and identify factors associated with its development. Data sources Systematic literature search in four databases. Study Selection Observational studies reporting the prevalence of NS after BA in adult patients with CD. Data extraction Data extraction and risk of bias assessment were performed by three independent investigators. Data synthesis Thirty-six studies, with a total of 1316 CD patients treated with BA, were included for the primary outcome. Pooled prevalence of NS was 26% (95% CI 22-31%), with moderate to high heterogeneity (I-2 67%, P < 0.01). The time from BA to NS varied from 2 months to 39 years. The prevalence of NS in the most recently published studies, where magnet resonance imaging was used, was 38% (95% CI 27-50%). The prevalence of treatment for NS was 21% (95% CI 18-26%). Relative risk for NS was not significantly affected by prior pituitary radiotherapy [0.9 (95% CI 0.5-1.6)] or pituitary surgery [0.6 (95% CI 0.4-1.0)]. Conclusions Every fourth patient with CD treated with BA develops NS, and every fifth patient requires pituitary-specific treatment. The risk of NS may persist for up to four decades after BA. Life-long follow-up is essential for early detection and adequate treatment of NS.
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5.
  • Zachrisson, Helene, et al. (author)
  • Diameter and compliance of the greater saphenous vein - effect of age and nitroglycerine
  • 2011
  • In: Clinical Physiology and Functional Imaging. - : Blackwell Publishing Ltd. - 1475-0961 .- 1475-097X. ; 31:4, s. 300-306
  • Journal article (peer-reviewed)abstract
    • Objectives: The greater saphenous vein (GSV) is commonly used in autologous vein graft surgery. GSV diameter has proven to influence graft patency, and furthermore venous compliance might be of importance. The purpose of the study was to evaluate the effect of age on GSV diameter and compliance, and to evaluate the effect of nitroglycerine (NTG). Methods: The diameter and compliance of the GSV, with and without NTG, were examined with B-mode ultrasound in 12 elderly (70.3 +/- 1.2 year) and 15 young (25.1 +/- 0.6 year) men. The GSV diameter at the thigh and calf level was measured at rest, after 6 min of venous stasis (60 mmHg) and after NTG administration. Pressure-area curves during a linear venous pressure decrease were produced. Venous compliance was calculated using the quadratic regression equation (area) = beta(0) + beta(1) (cuff pressure) + beta(2) (cuff pressure)(2). Results: GVS diameter between the groups showed significant lower diameter in elderly compared to young men (Pless than0.05). Venous occlusion increased GSV diameter in elderly men (Pless than0.01) as well as young men (Pless than0.001). NTG increased GSV diameter in elderly men (Pless than0.01) with an equal trend in young men. During venous occlusion, after administration of NTG, GSV diameter increased further in both elderly (Pless than0.01) and young men (Pless than0.001). GSV compliance was decreased in elderly (beta(1), 0.037 +/- 0019, beta(2), -0.000064 +/- 00017) versus young men (beta(1), 0.128 +/- 0.013, beta(2), -0.00010 +/- 000018) [Pless than0.001 (beta(1)), Pless than0.02 (beta(2))]. Conclusions: Baseline GSV diameter as well as GSV compliance is decreased in elderly men compared to the young subjects. As reduced GSV diameter as well as reduced compliance is related to decreased graft patency, these findings might be of importance for the uses of GSV as graft material in cardiovascular bypass surgery. The clinical value has to be clarified in future studies.
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6.
  • Aad, G, et al. (author)
  • Electron and photon energy calibration with the ATLAS detector using LHC Run 2 data
  • 2024
  • In: Journal of Instrumentation. - : Institute of Physics. - 1748-0221. ; 19:2
  • Journal article (peer-reviewed)abstract
    • This paper presents the electron and photon energy calibration obtained with the ATLAS detector using 140 fb−1 of LHC proton-proton collision data recorded at √s = 13 TeV between 2015 and 2018. Methods for the measurement of electron and photon energies are outlined, along with the current knowledge of the passive material in front of the ATLAS electromagnetic calorimeter. The energy calibration steps are discussed in detail, with emphasis on the improvements introduced in this paper. The absolute energy scale is set using a large sample of Z-boson decays into electron-positron pairs, and its residual dependence on the electron energy is used for the first time to further constrain systematic uncertainties. The achieved calibration uncertainties are typically 0.05% for electrons from resonant Z-boson decays, 0.4% at ET ∼ 10 GeV, and 0.3% at ET ∼ 1 TeV; for photons at ET ∼ 60 GeV, they are 0.2% on average. This is more than twice as precise as the previous calibration. The new energy calibration is validated using J/ → ee and radiative Z-boson decays. © 2024 Institute of Physics. All rights reserved.
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7.
  • Aad, G., et al. (author)
  • Integrated and differential fiducial cross-section measurements for the vector boson fusion production of the Higgs boson in the H → WW* → eνμν decay channel at 13 TeV with the ATLAS detector
  • 2023
  • In: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 108:7
  • Journal article (peer-reviewed)abstract
    • The vector-boson production cross section for the Higgs boson decay in the H→WW*→eνμν channel is measured as a function of kinematic observables sensitive to the Higgs boson production and decay properties as well as integrated in a fiducial phase space. The analysis is performed using the proton-proton collision data collected by the ATLAS detector in Run 2 of the LHC at √s=13  TeV center-of-mass energy, corresponding to an integrated luminosity of 139  fb−1. The different flavor final state is studied by selecting an electron and a muon originating from a pair of W bosons and compatible with the Higgs boson decay. The data are corrected for the effects of detector inefficiency and resolution, and the measurements are compared with different state-of-the-art theoretical predictions. The differential cross sections are used to constrain anomalous interactions described by dimension-six operators in an effective field theory.
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8.
  • Aad, G, et al. (author)
  • Measurement of Suppression of Large-Radius Jets and Its Dependence on Substructure in Pb+Pb Collisions at √sNN=5.02 TeV with the ATLAS Detector
  • 2023
  • In: Physical Review Letters. - 1079-7114. ; 131:17
  • Journal article (peer-reviewed)abstract
    • This letter presents a measurement of the nuclear modification factor of large-radius jets in Formula Presented Formula Presented collisions by the ATLAS experiment. The measurement is performed using Formula Presented and Formula Presented of Formula Presented and Formula Presented data, respectively. The large-radius jets are reconstructed with the anti-Formula Presented algorithm using a radius parameter of Formula Presented, by reclustering anti-Formula Presented Formula Presented jets, and are measured over the transverse momentum (Formula Presented) kinematic range of Formula Presented and absolute pseudorapidity Formula Presented. The large-radius jet constituents are further reclustered using the Formula Presented algorithm in order to obtain the splitting parameters, Formula Presented and Formula Presented, which characterize the transverse momentum scale and angular separation for the hardest splitting in the jet, respectively. The nuclear modification factor, Formula Presented, obtained by comparing the Formula Presented jet yields to those in Formula Presented collisions, is measured as a function of jet transverse momentum (Formula Presented) and Formula Presented or Formula Presented. A significant difference in the quenching of large-radius jets having single subjet and those with more complex substructure is observed. Systematic comparison of jet suppression in terms of Formula Presented for different jet definitions is also provided. Presented results support the hypothesis that jets with hard internal splittings lose more energy through quenching and provide a new perspective for understanding the role of jet structure in jet suppression. © 2023 CERN, for the ATLAS Collaboration.
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9.
  • Aad, G., et al. (author)
  • Measurement of the Sensitivity of Two-Particle Correlations in pp Collisions to the Presence of Hard Scatterings
  • 2023
  • In: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 131:16
  • Journal article (peer-reviewed)abstract
    • A key open question in the study of multiparticle production in high-energy pp collisions is the relationship between the “ridge”—i.e., the observed azimuthal correlations between particles in the underlying event that extend over all rapidities—and hard or semihard scattering processes. In particular, it is not known whether jets or their soft fragments are correlated with particles in the underlying event. To address this question, two-particle correlations are measured in pp collisions at √s=13  TeV using data collected by the ATLAS experiment at the LHC, with an integrated luminosity of 15.8  pb−1, in two different configurations. In the first case, charged particles associated with jets are excluded from the correlation analysis, while in the second case, correlations are measured between particles within jets and charged particles from the underlying event. Second-order flow coefficients, v2, are presented as a function of event multiplicity and transverse momentum. These measurements show that excluding particles associated with jets does not affect the measured correlations. Moreover, particles associated with jets do not exhibit any significant azimuthal correlations with the underlying event, ruling out hard processes contributing to the ridge.
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10.
  • Aad, G., et al. (author)
  • Observation of Single-Top-Quark Production in Association with a Photon Using the ATLAS Detector
  • 2023
  • In: Physical Review Letters. - : American Physical Society (APS). - 0031-9007 .- 1079-7114. ; 131:18
  • Journal article (peer-reviewed)abstract
    • This Letter reports the observation of single top quarks produced together with a photon, which directly probes the electroweak coupling of the top quark. The analysis uses 139  fb−1 of 13 TeV proton-proton collision data collected with the ATLAS detector at the Large Hadron Collider. Requiring a photon with transverse momentum larger than 20 GeV and within the detector acceptance, the fiducial cross section is measured to be 688±23(stat) , to be compared with the standard model prediction of at next-to-leading order in QCD.
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11.
  • Al-Shamkhi, Nasrin, 1985-, et al. (author)
  • Pituitary function before and after surgery for nonfunctioning pituitary adenomas-data from the Swedish Pituitary Register.
  • 2023
  • In: European journal of endocrinology. - : Bioscientifica. - 1479-683X .- 0804-4643. ; 189:2, s. 217-224
  • Journal article (peer-reviewed)abstract
    • Data on pre- and postoperative pituitary function in nonfunctioning pituitary adenomas (NFPA) are not consistent. We aimed to investigate pituitary function before and up to 5 years after transsphenoidal surgery with emphasis on the hypothalamic-pituitary-adrenal axis (HPA).Data from the Swedish Pituitary Register was used to analyze anterior pituitary function in 838 patients with NFPA diagnosed between 1991 and 2014. Patients who were reoperated or had received radiotherapy were excluded.Preoperative ACTH, TSH, LH/FSH, and GH deficiencies were reported in 31% (236/755), 39% (300/769), 51% (378/742), and 28% (170/604) of the patients, respectively. Preoperative median tumor volume was 5.0 (2.4-9.0) cm3. Among patients with preoperative, 1 year and 5 years postoperative data on the HPA axis (n = 428), 125 (29%) were ACTH-deficient preoperatively. One year postoperatively, 26% (32/125) of them had recovered ACTH function while 23% (70/303) patients had developed new ACTH deficiency. Thus, 1 year postoperatively, 163 (38%) patients were ACTH-deficient (P < .001 vs. preoperatively). No further increase was seen 5 years postoperatively (36%, P = .096). At 1 year postoperatively, recoveries in the TSH and LH/FSH axes were reported in 14% (33/241) and 15% (46/310), respectively, and new deficiencies in 22% (88/403) and 29% (83/288), respectively.Adrenocorticotrophic hormone deficiency increased significantly at 1 year postoperatively. Even though not significant, some patients recovered from or developed new deficiency between 1 and 5 years postoperatively. This pattern was seen in all axes. Our study emphasizes that continuous individual evaluations are needed during longer follow-up of patients operated for NFPA.
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12.
  • Arlien-Soborg, Mai C., et al. (author)
  • Acromegaly management in the Nordic countries: A Delphi consensus survey
  • 2024
  • In: Clinical Endocrinology. - : WILEY. - 0300-0664 .- 1365-2265.
  • Journal article (peer-reviewed)abstract
    • ObjectiveAcromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.MethodsA Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as >= 80% of panelists rating their agreement as >= 5 or <= 3 on the Likert-type scale.ResultsConsensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.ConclusionThis consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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13.
  • Arlien-Søborg, Mai C., et al. (author)
  • Acromegaly management in the nordic countries : a Delphi consensus survey
  • 2024
  • In: Clinical Endocrinology. - : John Wiley & Sons. - 0300-0664 .- 1365-2265.
  • Journal article (peer-reviewed)abstract
    • Objective: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.Methods: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1−7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale.Results: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.Conclusion: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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14.
  • Baumgardt, Magnus, et al. (author)
  • Specification of neuronal identities by feedforward combinatorial coding.
  • 2007
  • In: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 5:2, s. 0295-0308
  • Journal article (peer-reviewed)abstract
    • Neuronal specification is often seen as a multistep process: earlier regulators confer broad neuronal identity and are followed by combinatorial codes specifying neuronal properties unique to specific subtypes. However, it is still unclear whether early regulators are re-deployed in subtype-specific combinatorial codes, and whether early patterning events act to restrict the developmental potential of postmitotic cells. Here, we use the differential peptidergic fate of two lineage-related peptidergic neurons in the Drosophila ventral nerve cord to show how, in a feedforward mechanism, earlier determinants become critical players in later combinatorial codes. Amongst the progeny of neuroblast 5-6 are two peptidergic neurons: one expresses FMRFamide and the other one expresses Nplp1 and the dopamine receptor DopR. We show the HLH gene collier functions at three different levels to progressively restrict neuronal identity in the 5-6 lineage. At the final step, collier is the critical combinatorial factor that differentiates two partially overlapping combinatorial codes that define FMRFamide versus Nplp1/DopR identity. Misexpression experiments reveal that both codes can activate neuropeptide gene expression in vast numbers of neurons. Despite their partially overlapping composition, we find that the codes are remarkably specific, with each code activating only the proper neuropeptide gene. These results indicate that a limited number of regulators may constitute a potent combinatorial code that dictates unique neuronal cell fate, and that such codes show a surprising disregard for many global instructive cues.
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15.
  • Bengtsson, Daniel, 1975-, et al. (author)
  • Increased Mortality Persists after Treatment of Cushing's Disease: A Matched Nationwide Cohort Study
  • 2022
  • In: Journal of the Endocrine Society. - : The Endocrine Society. - 2472-1972. ; 6:6
  • Journal article (peer-reviewed)abstract
    • Context: Whether biochemical remission normalizes life expectancy in Cushing's disease (CD) patients remains unclear. Previous studies evaluating mortality in CD are limited by using the expected number of deaths in the background population instead of the actual number in matched controls. Objective and setting: To study mortality by time-to-event analysis in an unselected nationwide CD patient cohort. Design and participants: Longitudinal data from the Swedish Pituitary Register of 371 patients diagnosed with CD from 1991 to 2018 and information from the Swedish Cause of Death Register were evaluated. Four controls per patient (n = 1484) matched at the diagnosis date by age, sex, and residential area were included. Main outcome measures: Mortality and causes of death. Results: The median diagnosis age was 44 years (interquartile range 32-56), and the median follow-up was 10.6 years (5.7-18.0). At the 1-, 5-, 10-, 15-, and 20-year follow-ups, the remission rates were 80%, 92%, 96%, 91%, and 97%, respectively. Overall mortality was increased in CD patients compared with matched controls [hazard ratio (HR) 2.1 (95% CI 1.5-2.8)1. The HRs were 1.5 (1.02-2.2) for patients in remission at the last follow-up In = 303), 1.7 (1.03-2.8) for those in remission after a single pituitary surgery In = 177), and 5.6 (2.7-11.6) for those not in remission (n = 31). Cardiovascular diseases (32/66) and infections (12/66) were overrepresented causes of death. Conclusions: Mortality was increased in CD patients despite biochemical remission compared to matched controls. The study highlights the importance of careful comorbidity monitoring, regardless of remission status.
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16.
  • Bengtsson, Daniel, et al. (author)
  • Psychotropic Drugs in Patients with Cushing's Disease Before Diagnosis and at Long-Term Follow-Up: A Nationwide Study
  • 2021
  • In: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:6, s. 1750-1760
  • Journal article (peer-reviewed)abstract
    • Context: Psychiatric symptoms are common in Cushing's disease (CD) and seem only partly reversible following treatment. Objective: To investigate drug dispenses associated to psychiatric morbidity in CD patients before treatment and during long-term follow-up. Design: Nationwide longitudinal register-based study. Setting: University Hospitals in Sweden. Subjects: CD patients diagnosed between 1990 and 2018 (N = 372) were identified in the Swedish Pituitary Register. Longitudinal data was collected from 5 years before, at diagnosis, and during follow-up. Four matched controls per patient were included. Cross-sectional subgroup analysis of 76 patients in sustained remission was also performed. Main outcome measures: Data from the Swedish Prescribed Drug Register and the Patient Register. Results: In the 5-year period before and at diagnosis, use of antidepressants (odds ratio [OR] 2.2 [95% confidence interval (CI) 1.3-3.7]) and 2.3 [1.6-3.5]), anxiolytics [2.9 (1.6-5.3) and 3.9 (2.3-6.6)], and sleeping pills [2.1 (1.2-3.7) and 3.8 (2.4-5.9)] was more common in CD than controls. ORs remained elevated at 5-year follow-up for antidepressants [2.4 (1.53.9)] and sleeping pills [3.1 (1.9-5.3)]. Proportions of CD patients using antidepressants (26%) and sleeping pills (22%) were unchanged at diagnosis and 5-year follow-up, whereas drugs for hypertension and diabetes decreased. Patients in sustained remission for median 9.3 years (interquartile range 8.1-10.4) had higher use of antidepressants [OR 2.0 (1.1-3.8)] and sleeping pills [2.4 (1.3-4.7)], but not of drugs for hypertension. Conclusions: Increased use of psychotropic drugs in CD was observed before diagnosis and remained elevated regardless of remission status, suggesting persisting negative effects on mental health. The study highlights the importance of early diagnosis of CD, and the need for long-term monitoring of mental health.
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17.
  • Berggrund, Malin, et al. (author)
  • Protein Detection Using the Multiplexed Proximity Extension Assay (PEA) from Plasma and Vaginal Fluid Applied to the Indicating FTA Elute Micro Card™
  • 2016
  • In: Journal of Circulating Biomarkers. - : SAGE Publications. - 1849-4544. ; 5
  • Journal article (peer-reviewed)abstract
    • The indicating FTA elute micro card? has been developed to collect and stabilize the nucleic acid in biological samples and is widely used in human and veterinary medicine and other disciplines. This card is not recommended for protein analyses, since surface treatment may denature proteins. We studied the ability to analyse proteins in human plasma and vaginal fluid as applied to the indicating FTA elute micro card? using the sensitive proximity extension assay (PEA). Among 92 proteins in the Proseek Multiplex Oncology Iv2 panel, 87 were above the limit of detection (LOD) in liquid plasma and 56 among 92 above LOD in plasma applied to FTA cards. Washing and protein elution protocols were compared to identify an optimal method. Liquid-based cytology samples showed a lower number of proteins above LOD than FTA cards with vaginal fluid samples applied. Our results demonstrate that samples applied to the indicating FTA elute micro card? are amendable to protein analyses, given that a sensitive protein detection assay is used. The results imply that biological samples applied to FTA cards can be used for DNA, RNA and protein detection.
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18.
  • Blomberg, Carl, et al. (author)
  • Randomized Trials of Systemic Medically-treated Malignant Mesothelioma : A Systematic Review
  • 2015
  • In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 35:5, s. 2493-2501
  • Research review (peer-reviewed)abstract
    • Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy mainly localized to the pleura. Malignant mesothelioma grows highly invasive into surrounding tissue and has a low tendency to metastasize. The median overall survival (OS) of locally advanced or metastatic disease without treatment is 4-13 months but, during recent years, improvement in survival has been achieved since treatment for patients with mesothelioma has improved with better palliative care, systemic medical treatment, surgery and improved diagnostics methods. The present review aims at describing available data from randomized trials considering systemic medical treatment for this patient category.
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19.
  • Bolander, Åsa, 1977- (author)
  • Prognostic Factors in Malignant Melanoma
  • 2008
  • Doctoral thesis (other academic/artistic)abstract
    • Because of the failure so far to find effective treatment for patients with advanced stages of melanoma, increasing efforts have been made to find prognostic factors identifying patients in the risk zone for development of metastasis.This thesis investigates the prognostic powers of a few selected serological and immunohistochemical biomarkers.In the first and second study, patients operated on for localized malignant melanoma were investigated regarding the prognostic impact of angiogenic serological markers and circulating levels of S100. We concluded that the S100 assays, especially S100BB, are potential biomarkers in patients with malignant melanoma, correlated to both survival and disease free survival. However, no such conclusion could be drawn from the first study, where we found no correlation to survival and investigated angiogenic markers.In the third and fourth study four new potential immunohistochemical biomarkers where investigated in collaboration with the Swedish Human Protein Atlas Program, and those where TRP-1, galectin-1, DLG5 and syntaxin-7.We found that TRP-1 correlated inversely with tumor stage and galectin-1 correlated to Ki-67.DLG5 showed a significant inverse correlation to Ki67 and the expression of STX7 was inversely correlated to tumor stage, suggesting that decreased expression is associated with more aggressive tumors.None of the investigated markers in study III and IV correlated with disease free survival or overall survival.In the fifth and last study, we examined the expression of SOX10, a transcription factor, in different melanocytic lesions. Also, a proliferation assay was carried out in a human melanoma cell line. The results reveal the presence of SOX10 in different melanocytic lesions, with a weak inverse correlation to survival and a significant inverse correlation to T-stage. A significant decrease in proliferation rate for SOX10 silenced cells was found and our data also suggests an increased migratory response in SOX10 silenced cells.
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20.
  • Bolander, Åsa, et al. (author)
  • Serological and immunohistochemical analysis of S100 and derivatives as markers for prognosis of newly operated malignant melanoma patients
  • 2008
  • In: Melanoma research. - 0960-8931 .- 1473-5636. ; 18:6, s. 412-419
  • Journal article (peer-reviewed)abstract
    • The incidence of cutaneous malignant melanoma is rising, and tumour markers are attracting attention as a possible alternative to clinical examination in the follow-up situation. S100 is the preferred marker for malignant melanoma, and correlation between serum S100 and disease relapse and survival has been reported. S100 tests previously used in clinical studies were specified poorly regarding reactivity with S100A1B and S100BB. In this study, a newly designed S100 assay (designed to measure exclusively S100A1B and S100BB) and two newly developed serological assays, S100A1B, and S100BB, were investigated postoperatively in patients undergoing radical surgery for cutaneous malignant melanoma. Additionally, immunohistochemical analysis of S100A4 was performed on the primary malignant melanoma using tissue microarrays. The primary aim of the study was to investigate whether any of these assays, either singly or in combination, can contribute additional information concerning increased risk of relapse and death because of malignant melanoma. In total, 98 patients (54 males, 44 females) with malignant melanoma were included in the study. As a continuous variable, S100BB (P=0.016) was associated statistically with increased risk of relapse; this was not the case for increased values of either S100 (P=0.11) or S100A1B (P=0.92). The Kaplan-Meier overall survival as well as disease specific survival curve for the S100 serum level demonstrated a statistically significant association with better survival if the patient had a S100 level
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21.
  • Bolander, Åsa, et al. (author)
  • The Role of Circulating Angiogenic Factors in Patients Operated on for Localized Malignant Melanoma
  • 2007
  • In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:5A, s. 3211-3217
  • Journal article (peer-reviewed)abstract
    • Malignant melanoma is a disease capable of rapid progression and rapidly developing metastases. Angiogenesis is a key event signalling tumour progression and elevated levels of angiogenic markers may indicate metastatic disease. No previously published work has, so far, examined plasma vascular endothelial growth factor (VEGF) and its receptor, VEGFR-1, in melanoma. This study investigated circulating levels of the angiogenic factors, VEGF-A and -D, their receptors 1-3 and hepatocyte growth factor (HGF)/scatter factor, in patients shortly after primary surgery for localized malignant melanoma. Elevated circulating levels of VEGF and its receptors, and of HGF, were found postoperatively, possibly derived from the reactive stroma adjacent to the tumours. Using univariate analysis, a correlation between levels of VEGFR-1 and relapse was found, but a correlation between the investigated angiogenic factors and survival could not be established. The results of the present study indicate that production of these angiogenic factors may be due to sources other than malignant melanoma cells.
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22.
  • Bosworth, H. B., et al. (author)
  • Medication adherence: a call for action
  • 2011
  • In: American heart journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 162:3, s. 412-24
  • Journal article (peer-reviewed)abstract
    • Poor adherence to efficacious cardiovascular-related medications has led to considerable morbidity, mortality, and avoidable health care costs. This article provides results of a recent think-tank meeting in which various stakeholder groups representing key experts from consumers, community health providers, the academic community, decision-making government officials (Food and Drug Administration, National Institutes of Health, etc), and industry scientists met to evaluate the current status of medication adherence and provide recommendations for improving outcomes. Below, we review the magnitude of the problem of medication adherence, prevalence, impact, and cost. We then summarize proven effective approaches and conclude with a discussion of recommendations to address this growing and significant public health issue of medication nonadherence.
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23.
  • Bulatovic, Ines (author)
  • Investigating aerosol effects on stratocumulus clouds through large-eddy simulation
  • 2022
  • Doctoral thesis (other academic/artistic)abstract
    • Clouds have a large impact on Earth’s radiative budget by reflecting, absorbing and re-emitting radiation. They thus play a critical role in the climate system. Nevertheless, cloud radiative effects in a changing climate are highly uncertain. Atmospheric aerosol particles are another factor affecting Earth’s climate but the magnitude of their influence is also associated with high uncertainty. Therefore, an accurate representation of aerosol-cloud interactions in models is critical for having confidence in future climate projections. This thesis investigates aerosol impacts on cloud microphysical and radiative properties through numerical modelling, more specifically large-eddy simulation (LES). Moreover, the thesis investigates how the simulated cloud response to changes in the aerosol population depends on the model description of different processes. Mixed-phase stratocumulus (MPS) clouds are especially problematic to simulate for models on all scales. These clouds consist of a mixture of supercooled water and ice in the same volume and are therefore potentially thermodynamically unstable. MPS clouds over the central (north of 80° N) Arctic Ocean are particularly sensitive to aerosol changes due to the relatively clean atmospheric conditions in this region. At the same time, the clouds also have an important impact on the Arctic surface radiative budget. Therefore, this thesis mostly focuses on Arctic MPS clouds.Simulations of a typical subtropical marine stratocumulus cloud showed that the aerosol-cloud forcing depends on the model treatment for calculating the cloud droplet number concentration (CDNC). The simulated change in the top of the atmosphere shortwave radiation due to increased aerosol number concentrations was almost three times as large when the CDNC was prescribed compared to when the CDNC was prognostic. Simulations of a central Arctic summertime low-level MPS cloud confirmed that the chemical composition and the size of aerosol particles both can play an important role in determining the efficiency of an aerosol to act as cloud condensation nuclei - and thus influence cloud properties. However, the hygroscopicity of the aerosol particle was only important if the particles were small in size (i.e., if they correspond to the Aitken mode size) or if they were close to hydrophobic. Further, it was also found that Aitken mode particles can significantly change microphysical and radiative properties of central Arctic MPS if the concentration of larger particles (i.e., corresponding to the accumulation mode) is less than approximately 10-20 cm-3. One of the most recent research expeditions in the central Arctic (in the summer of 2018) was characterized by a high occurrence of multiple cloud layers. Namely, the boundary layer structure consisted of two MPS, one located close to the surface and one at the top of the boundary layer. Large-eddy simulations of an observed case with this particular cloud structure showed that the two-layer boundary-layer clouds are persistent unless the aerosol number concentrations are low (< 5 cm-3) or the wind speed is high (≥ 8.5 m s-1). In the model, low aerosol numbers led to a dissipation of the upper cloud layer while the lower cloud layer dissipated if the wind speed was strong. Changes in the optical thickness and cloud emissivity of each individual cloud layer of the two-layer cloud structure were found to substantially impact the surface radiative fluxes.
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24.
  • Casar Borota, Olivera, et al. (author)
  • Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations
  • 2021
  • In: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:4, s. 1183-1194
  • Journal article (peer-reviewed)abstract
    • Context: Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors. Objective: To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs. Design: We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored. Results: Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; 28%) than in those with APTs (4/30;13%). Lack of ATRX was most common in the corticotroph tumors, 7/22 (32%), versus tumors of the Pit-1 lineage, 2/24 (8%). Loss-of-function ATRX mutations were found in all 9 ATRX immunonegative cases: nonsense mutations (n = 4), frameshift deletions (n = 4), and large deletions affecting 22-28 of the 36 exons (n = 3). More than 1 ATRX gene defect was identified in 2 PCs. Conclusion: ATRX mutations occur in a subset of APTs and are more common in corticotroph tumors. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumors.
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25.
  • Davidson, Lee Ti, et al. (author)
  • Admission of patients with chest pain and/or breathlessness from the emergency department in relation to risk assessment and copeptin levels - an observational study
  • 2022
  • In: Upsala Journal of Medical Sciences. - : UPSALA MED SOC. - 0300-9734 .- 2000-1967. ; 127:1
  • Journal article (peer-reviewed)abstract
    • Background: One of the most critical decisions that emergency department (ED) physicians make is the discharge versus admission of patients. We aimed to study the association of the decision in the ED to admit patients with chest pain and/or breathlessness to a ward with risk assessment using the Rapid Emergency Triage and Treatment System (RETTS), the National Early Warning Score (NEWS), and plasma levels of the biomarkers copeptin, midregional proadrenomedulin (MR-proADM), and midregional proatrial natriuretic peptide (MR-proANP). Methods: Patients presenting at the ED with chest pain and/or breathlessness with less than one week onset were enrolled. Patients were triaged according to RETTS. NEWS was calculated from the vital signs retrospectively. Results: Three hundred and thirty-four patients (167 males), mean age 63.8 +/- 16.8 years, were included. Of which, 210 (62.8%) patients complained of chest pain, 65 (19.5%) of breathlessness, and 59 (17.7%) of both. Of these, 176 (52.7%) patients were admitted to a ward, and 158 (47.3%) patients were discharged from the ED. In binary logistic models, age, gender, vital signs (O-2 saturation and heart rate), NEWS class, and copeptin were associated with admission to a ward from the ED. In receiver-operating-characteristics (ROC) analysis, copeptin had an incremental predictive value compared to NEWS alone (P = 0.002). Conclusions: Emergency physicians decisions to admit patients with chest pain and/or breathlessness from the ED to a ward are related to age, O-2 saturation, heart rate, NEWS category, and copeptin. As an independent predictive marker for admission, early analysis of copeptin might be beneficial when improving patient pathways at the ED.
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26.
  • Eckardt, Johanna, et al. (author)
  • Long-term frozen storage of wheat bread and dough : Effect of time, temperature and fibre on sensory quality, microstructure and state of water
  • 2013
  • In: Journal of Cereal Science. - : Elsevier BV. - 0733-5210 .- 1095-9963. ; 57:1, s. 125-133
  • Journal article (peer-reviewed)abstract
    • The objective of this study was to determine effect of storage time, storage temperature and addition of fibre on sensory quality, state of water, microstructure and texture of bread and dough. Samples with and without fibre, were stored frozen for 2, 3.5 and 6 months at temperatures of -19, -16 and -8 °C as dough and bread. Sensory quality was evaluated by a trained analytical panel. Microstructure was analysed by light microscopy. Texture measurements were performed on bread, and the state of water was measured by differential scanning calorimetry. Bread without fibre stored as dough at -19 °C was the sample most like freshly baked bread. Sensory evaluation also confirmed that quality of the final bread was improved if samples were stored as dough compared to stored as bread. The microstructure had larger gaps between the starch and gluten phases when stored at warmer temperatures, due to retrogradation of starch, dehydration of gluten and water migration. DSC measurements showed that bread stored at -19 °C gained extra amount of freezable water, but lost ice after storage at -8 °C. Texture measurements showed that firmness increased with extended storage time. Bread stored at -8 °C had lowest quality in all measurements.
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27.
  • Einarsdottir, Margret, et al. (author)
  • High Mortality Rate in Oral Glucocorticoid Users: A Population-Based Matched Cohort Study
  • 2022
  • In: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 13
  • Journal article (peer-reviewed)abstract
    • ObjectiveThe aim of the study was to investigate all-cause and disease-specific mortality in a large population-based cohort of oral glucocorticoid (GC) users. MethodsThis was a retrospective, matched cohort study. Information on dispensed prescriptions was obtained from the Swedish Prescribed Drug Register. The cause of death was obtained from the Swedish Cause-of-Death Registry. Patients receiving prednisolone >= 5 mg/day (or equivalent dose of other GC) for >= 21 days between 2007-2014 were included. For each patient, one control subject matched for age and sex was included. The study period was divided into 3-month periods and patients were divided into groups according to a defined daily dose (DDD) of GC used per day. The groups were: Non-users (0 DDD per day), low-dose users (>0 but <0.5 DDD per day), medium-dose users (0.5-1.5 DDD per day) and high-dose users (>1.5 DDD per day). Hazard ratios (HRs), unadjusted and adjusted for age, sex and comorbidities, were calculated using a time-dependent Cox proportional hazard model. ResultsCases (n=223 211) had significantly higher all-cause mortality compared to controls (HR adjusted for age, sex and comorbidities 2.08, 95% confidence interval 2.04 to 2.13). After dividing the cases into subgroups, adjusted HR was 1.31 (1.28 to 1.34) in non-users, 3.64 (3.51 to 3.77) in low-dose users, 5.43 (5.27 to 5.60) in medium-dose users and, 5.12 (4.84 to 5.42) in high-dose users. The highest adjusted hazard ratio was observed in high-dose users for deaths from sepsis 6.71 (5.12 to 8.81) and pulmonary embolism 7.83 (5.71 to 10.74). ConclusionOral GC users have an increased mortality rate compared to the background population, even after adjustment for comorbidities. High-dose users have an increased risk of dying from sepsis, and pulmonary embolism compared to controls. Whether the relationship between GC exposure and the excess mortality is causal remains to be elucidated.
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28.
  • Einarsdottir, Margret, et al. (author)
  • High prescription rate of oral glucocorticoids in children and adults: a retrospective cohort study from Western Sweden.
  • 2020
  • In: Clinical endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 92:1, s. 21-28
  • Journal article (peer-reviewed)abstract
    • Glucocorticoids (GCs) are a cornerstone in treating various common and uncommon diseases. The aim of this study was to estimate the prevalence of GC use in terms of doses associated with risk of tertiary adrenal insufficiency in adults and children, and treatment indications.This was a retrospective cohort study. Information on dispensed prescriptions was obtained from the Swedish Prescribed Drug Register. Patients with prescriptions of prednisolone (or equivalent dose of other GCs) ≥5 mg daily for ≥21 days between 2007-2014 were included. Information on concurrent diseases was obtained from the Swedish National Patient Register and the Västra Götaland Regional Healthcare Database.Of 1,585,335 inhabitants in Västra Götaland County, 223,211 were included in the study (women 55.6%). Mean age was 48 ± 24 years. Period prevalence of oral GC use during the 8-year study period was 14.1%. The highest prevalence (27.4%) was in men aged 80-89 years and lowest (7.5%) in men 10-19 years of age. The period prevalence in children 0-9 years of age was 10.6%. COPD and asthma were the most common indications for treatment (17.2%) followed by allergy (12.5%), and malignant neoplasms (11.5%). Allergy was the most frequent indication (20.5%) in children and adolescents.Between 2007-2014, every seventh inhabitant in western Sweden received a GC prescription at doses associated with risk of developing tertiary adrenal insufficiency. These findings illustrate the importance of awareness of the potential development of tertiary adrenal insufficiency in both pediatric and adult patients.
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29.
  • Ekberg, Olle, et al. (author)
  • Flow properties of oral contrast medium formulations depend on the temperature
  • 2010
  • In: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 51:4, s. 363-367
  • Journal article (peer-reviewed)abstract
    • Background: During the therapeutic videofluoroscopic examination of swallowing, gradation of bolus volume, texture, and viscosity can be implemented to determine the optimal bolus characteristics in that particular patient. When a thickened liquid is given to a dysphagic patient it is served at room temperature. However, in these patients with a delayed oral and/or pharyngeal stage of swallow, the bolus is held for a long time in the oral cavity. The temperature of the thickened liquid thereby increases. Purpose: To study the rheological exploration (variation of viscosity with temperature) of thickened food used for radiologic swallowing examinations in patients with oral and pharyngeal dysfunction, in particular in mixtures of barium sulfate suspensions and in iodine solutions. Material and Methods: Deep-frozen mango purée was thawed at room temperature. It was then mixed with barium sulfate contrast medium to a density of 25% w/w. Resorce® Thicken Up was mixed at room temperature at two concentrations: 4.3% w/w (4.5 g thickener + 100 g distilled water) and 6.0% w/w (4.5 g thickener + 70 g distilled water). The thickener consisted of modified corn starch. Resorce® Thicken Up was also mixed at room temperature with two concentrations of an iodine contrast material, iohexol (Omnipaque®, 350 mg I/ml). The two concentrations were: 4.3% w/w (4.5 g thickener + 100 g iohexol) and 6% w/w (6 g thickener + 100 g iohexol). Measurements were carried out from 20°C to 37°C using a Stresstech HR rheometer. The rheometer was equipped with a concentric cylinder measuring system (inner cylinder 15 mm). Results: The samples containing thickener in water as well as in iohexol showed a dependence on thickener concentration and temperature. The mango purée with barium sulfate displayed very small temperature dependence. The thickener solutions in iohexol had significantly higher viscosity compared with the other thickener solutions and the mango purée. The relative decrease shows that mango purée, the 6% thickener solution in water, and solutions with iohexol exhibited similar relative viscosity change at different temperatures. Conclusion: Our conclusion is therefore that it is important always to make the solution with high precision. It is also of importance to observe how long the patient keeps the bolus in the mouth. This might vary and actually it may not be possible to influence this factor. When different types of thickeners are compared, it is important to take into account the temperature at which the thickener is observed.
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30.
  • Ekman, Asa, et al. (author)
  • Carbon partitioning between oil and carbohydrates in developing oat (Avena sativa L.) seeds
  • 2008
  • In: Journal of Experimental Botany. - : Oxford University Press (OUP). - 0022-0957 .- 1460-2431. ; 59:15, s. 4247-4257
  • Journal article (peer-reviewed)abstract
    • Cereals accumulate starch in the endosperm as their major energy reserve in the grain. In most cereals the embryo, scutellum, and aleurone layer are high in oil, but these tissues constitute a very small part of the total seed weight. However, in oat (Avena sativa L.) most of the oil in kernels is deposited in the same endosperm cells that accumulate starch. Thus oat endosperm is a desirable model system to study the metabolic switches responsible for carbon partitioning between oil and starch synthesis. A prerequisite for such investigations is the development of an experimental system for oat that allows for metabolic flux analysis using stable and radioactive isotope labelling. An in vitro liquid culture system, developed for detached oat panicles and optimized to mimic kernel composition during different developmental stages in planta, is presented here. This system was subsequently used in analyses of carbon partitioning between lipids and carbohydrates by the administration of C-14-labelled sucrose to two cultivars having different amounts of kernel oil. The data presented in this study clearly show that a higher amount of oil in the high-oil cultivar compared with the medium-oil cultivar was due to a higher proportion of carbon partitioning into oil during seed filling, predominantly at the earlier stages of kernel development.
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31.
  • Ekman, Inger, 1952, et al. (author)
  • The person-centred approach to an ageing society
  • 2013
  • In: European Journal for Person Centered Healthcare. - : University of Buckingham Press. - 2052-5656 .- 2052-5648. ; 1:1, s. 132-137
  • Journal article (peer-reviewed)abstract
    • Modern care is often based on investigations such as laboratory markers and imaging - for example, x-ray or ultrasound. The results contribute to a diagnosis and, if judged necessary, treatment is initiated. This diseased-oriented approach is the prevailing mode of management in modern medicine. In contrast, person-centered care (PCC) takes the point of departure from each person´s subjective experience of illness and its impact on daily life. A patient is considered as a person with emotions and feelings. PCC is considered present within clinical care according to a definition articulated by the Centre for Person Centred Care at the University of Gothenburg (GPCC) when three core components are present: elicitation of a detailed patient narrative; formulated partnership between caregiver and patient and documentation of the partnership in the patient record. Accordingly, when there is an illness requiring care and the person is attended using these components, PCC is being applied. In most situations today, PCC is not applied as the narrative is not fully elicited or the partnership and/or the documentation are not included. It is proposed that the challenge to Society arising from changing demographics can be addressed by implementing PCC and creating an alternative to existing healthcare. The importance and benefits of such an approach on a wider scale is not yet clear as research has been limited to date. Studies in selected patient populations (heart failure and hip fractures), however, have shown promising results. As the population ages, there will be a dramatic increase in healthcare consumption. Even with technological developments, there will be a need for tremendous resources to be dedicated to care. A new organization and attitude from healthcare policymakers and providers above and beyond the present model appears required in order to respond to this demand. As part of such change, person-centred care, with the interaction between healthcare providers and the person of the patient, can facilitate, compensate and develop more effective healthcare services for the future.
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32.
  • Ekman, John, et al. (author)
  • Dynamics of pre-shift and post-shift lung function parameters among wood workers in Ghana
  • 2023
  • In: Annals of occupational and environmental medicine. - : BioMed Central (BMC). - 2052-4374. ; 35
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Diseases affecting the lungs and airways contribute significantly to the global burden of disease. The problem in low- and middle-income countries appears to be exacerbated by a shift in global manufacturing base to these countries and inadequate enforcement of environmental and safety standards. In Ghana, the potential adverse effects on respiratory function associated with occupational wood dust exposure have not been thoroughly investigated.METHODS: Sixty-four male sawmill workers and 64 non-woodworkers participated in this study. The concentration of wood dust exposure, prevalence and likelihood of association of respiratory symptoms with wood dust exposure and changes in pulmonary function test (PFT) parameters in association with wood dust exposure were determined from dust concentration measurements, symptoms questionnaire and lung function test parameters.RESULTS: Sawmill workers were exposed to inhalable dust concentration of 3.09 ± 0.04 mg/m3 but did not use respirators and engaged in personal grooming habits that are known to increase dust inhalation. The sawmill operators also showed higher prevalence and likelihoods of association with respiratory symptoms, a significant cross-shift decline in some PFT parameters and a shift towards a restrictive pattern of lung dysfunction by end of daily shift. The before-shift PFT parameters of woodworkers were comparable to those of non-woodworkers, indicating a lack of chronic effects of wood dust exposure.CONCLUSIONS: Wood dust exposure at the study site was associated with acute respiratory symptoms and acute changes in some PFT parameters. This calls for institution and enforcement of workplace and environmental safety policies to minimise exposure at sawmill operating sites, and ultimately, decrease the burden of respiratory diseases.
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33.
  • Ekman, M., et al. (author)
  • Tool qualification for safety related systems
  • 2014
  • In: Ada User Journal. - 1381-6551. ; 35, s. 47-54
  • Journal article (peer-reviewed)abstract
    • Tools used in the development of safety related software applications need to be qualified as safe. That is, the tools cannot be allowed to introduce hazardous faults into the application, e.g., a compiler shall not generate dangerous code due to failure of the compiler. In many cases laws and regulations require the product development of safety related applications to comply with industry sector specific safety standards. Examples of such standards include EN50129/50128 for railway applications, ISO/EN13849 for machines with moving parts, DO-178B/C for avionics, or IS026262 for cars. These standards require the use of a rigorous development and maintenance process. The standards are also mainly intended to be used when developing systems from scratch. However, most development and test tools are not developed from scratch according to the rigorous processes of these standards. In order to address this issue, some of the standards provide means for qualifying existing tools as a more lightweight and pragmatic alternative to a regular certification process. In this paper we analyze the concept of these qualification approaches. The result of the analysis in our contribution includes a set of approaches that can be applied individually or as a combination in order to reduce the effort needed for qualifying tools. As a running example we use one of the most flexible but at the same time dangerous, even prohibited, maintenance techniques available: dynamic instrumentation of executing code. With this example, we describe how exceptions in these standards can be utilized in order to qualify a dynamic instrumentation tool with a minimal effort, without following the process of tool certification as defined by the standards.
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34.
  • Ekman, Simon, et al. (author)
  • Esophageal cancer : current and emerging therapy modalities
  • 2008
  • In: Expert Review of Anticancer Therapy. - : Informa UK Limited. - 1473-7140 .- 1744-8328. ; 8:9, s. 1433-1448
  • Research review (peer-reviewed)abstract
    • During the last few years, there has been a gradual increase in treatment options for patients with esophageal malignancies. Several clinical studies have been performed, covering not only radiation and chemotherapy, but also the introduction of novel biological agents into the treatment arsenal. Patients with esophageal carcinoma are now offered second-line and sometimes even third-line treatments, and the number of research protocols is increasing. Despite the newly awakened interest in this malignancy, the overall 5-year survival rate has remained at approximately 10% since the 1980s. This review contains a compilation of available studies of esophageal malignancies and discusses current treatment options as well as newly developed therapies targeted at growth factor receptors.
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35.
  • Ekman, Urban, et al. (author)
  • The MemClin project : a prospective multi memory clinics study targeting early stages of cognitive impairment
  • 2020
  • In: BMC Geriatrics. - : BMC. - 1471-2318. ; 20
  • Journal article (peer-reviewed)abstract
    • Background: There remains a lack of large-scale clinical studies of cognitive impairment that aim to increase diagnostic and prognostic accuracy as well as validate previous research findings. The MemClin project will amass large quantities of cross-disciplinary data allowing for the construction of robust models to improve diagnostic accuracy, expand our knowledge on differential diagnostics, strengthen longitudinal prognosis, and harmonise examination protocols across centres. The current article describes the Memory Clinic (MemClin) project's study-design, materials and methods, and patient characteristics. In addition, we present preliminary descriptive data from the ongoing data collection.Methods: Nine out of ten memory clinics in the greater Stockholm area, which largely use the same examination methods, are included. The data collection of patients with different stages of cognitive impairment and dementia is coordinated centrally allowing for efficient and secure large-scale database construction. The MemClin project rest directly on the memory clinics examinations with cognitive measures, health parameters, and biomarkers.Results: Currently, the MemClin project has informed consent from 1543 patients. Herein, we present preliminary data from 835 patients with confirmed cognitive diagnosis and neuropsychological test data available. Of those, 239 had dementia, 487 mild cognitive impairment (MCI), and 104 subjective cognitive impairment (SCI). In addition, we present descriptive data on visual ratings of brain atrophy and cerebrospinal fluid markers.Conclusions: Based on our current progress and preliminary data, the MemClin project has a high potential to provide a large-scale database of 1200-1500 new patients annually. This coordinated data collection will allow for the construction of improved diagnostic and prognostic models for neurodegenerative disorders and other cognitive conditions in their naturalistic setting.
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36.
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37.
  • Gyllenhammar, Måns, et al. (author)
  • The Association Between Temporal Atrophy and Episodic Memory Is Moderated by Education in a Multi-Center Memory Clinic Sample
  • 2023
  • In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 92:2, s. 605-614
  • Journal article (peer-reviewed)abstract
    • Background: Cognitive reserve (CR) is hypothesized to partially explain the discrepancy between Alzheimer’s disease related brain pathology and cognitive performance. Educational attainment is often used as a proxy for CR.Objective: To examine the association of years of education and the relationship between atrophy in the medial temporal lobe and episodic memory, in a cross-sectional ecological multi-center memory clinic cohort.Methods: Included patients (n = 702) had undergone memory clinic examination and were diagnosed with subjective cognitive impairment (n = 99), mild cognitive impairment (n = 471), or dementia (n = 132). Total years of education were used as a moderating variable and neuropathology was operationalized as visual ratings of medial temporal lobe atrophy (MTA) on magnetic resonance imaging and computer tomography images. Weighted least squares regression and multiple regression were used to analyze moderation and the effect of education separately by diagnostic group. A composite score of two episodic memory tests constituted the dependent variable.Results: After controlling for age and gender the interaction term between MTA and years of education was significant indicating moderation. In particular, the regression model showed that at low levels of MTA, high education individuals had better episodic memory performance. However, at higher MTA levels, high education individuals had the lowest episodic memory performance. Education had a significant positive effect on episodic memory in SCI and MCI, but not dementia.Conclusion: These results extend the findings of education moderating the effect of MTA on cognition to a naturalistic memory clinic setting. Implications of the findings for theories on CR are discussed.
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38.
  • Himonakos, Christos, et al. (author)
  • Long-term Follow-up of 84 Patients With Giant Prolactinomas-A Swedish Nationwide Study.
  • 2023
  • In: The Journal of clinical endocrinology and metabolism. - : Oxford University Press. - 1945-7197 .- 0021-972X. ; 108:12
  • Journal article (peer-reviewed)abstract
    • To describe the clinical presentation and treatment outcomes in a nationwide cohort of patients with giant prolactinomas.Register-based study of patients with giant prolactinomas [serum prolactin (PRL) > 1000 µg/L, tumor diameter ≥40 mm] identified in the Swedish Pituitary Register 1991-2018.Eighty-four patients [mean age 47 (SD ±16) years, 89% men] were included in the study. At diagnosis, the median PRL was 6305 µg/L (range 1450-253 000), the median tumor diameter was 47 mm (range 40-85), 84% of the patients had hypogonadotropic hypogonadism, and 71% visual field defects. All patients were treated with a dopamine agonist (DA) at some point. Twenty-three (27%) received 1 or more additional therapies, including surgery (n = 19), radiotherapy (n = 6), other medical treatments (n = 4), and chemotherapy (n = 2). Ki-67 was ≥10% in 4/14 tumors. At the last follow-up [median 9 years (interquartile range (IQR) 4-15)], the median PRL was 12 µg/L (IQR 4-126), and the median tumor diameter was 22 mm (IQR 3-40). Normalized PRL was achieved in 55%, significant tumor reduction in 69%, and combined response (normalized PRL and significant tumor reduction) in 43%. In the primary DA-treated patients (n = 79), the reduction in PRL or tumor size after the first year predicted the combined response at the last follow-up (P < .001 and P = .012, respectively).DAs effectively reduced PRL and tumor size, but approximately 1 patient out of 4 needed multimodal treatment. Our results suggest that the response to DA after 1 year is useful for identifying patients who need more careful monitoring and, in some cases, additional treatment.
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39.
  • Hirschberg, Daniel, et al. (author)
  • Altered immunoglobulin G glycosylation in patients with isolated hyperprolactinaemia
  • 2021
  • In: PLOS ONE. - San Francisco, USA : Public Library of Science. - 1932-6203. ; 16:2
  • Journal article (peer-reviewed)abstract
    • Prolactin is a peptide hormone produced in the anterior pituitary, which increase in several physiological and pathological situations. It is unclear if hyperprolactinaemia may affect glycosylation of immunoglobulin G (IgG). Twenty-five patients with hyperprolactinemia and 22 healthy control subjects were included in the study. The groups had similar age and gender distribution. A panel of hormonal and haematological analyses, creatinine, glucose, liver enzymes and immunoglobulins were measured by routine clinical methods. IgG was purified from serum by Protein G Sepharose. Sialic acid was released from IgG by use of neuraminidase followed by quantification on high performance anion-exchange chromatography with pulsed amperometric detection. Tryptic glycopeptides of IgG was analysed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Hormone and immunoglobulin levels were similar in the two groups, except for IgA and prolactin. Significantly higher IgG1 and IgG2/3 galactosylation was found in the patient group with hyperprolactinaemia compared to controls. (A significant correlation between prolactin and IgG2/3 galactosylation (Rs 0.61, p<0.001) was found for samples with prolactin values below 2000 mIU/L. The relative amount of sialylated and bisecting glycans on IgG did not differ between patients and controls. The four macroprolactinaemic patients showed decreased relative amount of bisecting IgG2/3 glycans. Hyperprolactinaemia was found to be associated with increased galactosylation of IgG1 and IgG2/3. This may have impact on IgG interactions with Fc-receptors, complement and lectins, and consequently lead to an altered immune response.
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40.
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41.
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42.
  • Jonsdottir, Ingibjörg H, 1966, et al. (author)
  • Monocyte chemotactic protein-1 (MCP-1) and growth factors called into question as markers of prolonged psychosocial stress.
  • 2009
  • In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:11
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Psychosocial stress is becoming a major contributor to increased mental ill-health and sick leave in many countries. Valid markers of chronic stress would be valuable for diagnostic and prognostic purposes. A recent study suggested monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as markers of chronic stress. We aimed to confirm these potential biomarkers of prolonged psychosocial stress in female patients. METHODOLOGY/PRINCIPAL FINDINGS: Circulating levels of MCP-1, EGF and VEGF, along with several other cytokines, were measured in plasma from 42 female patients suffering from exhaustion due to prolonged psychosocial stress and 42 control subjects, using a protein biochip immunoassay. There were no significant differences between patients and controls in any of the cytokines or growth factors analyzed. Furthermore, when using a different protein bioassay and reanalyzing MCP-1 and VEGF in the same samples, markedly different levels were obtained. To further explore if inflammation is present in patients with exhaustion, the classical inflammatory marker C-reactive protein (CRP) was measured in another group of patients (n=89) and controls (n=88) showing a small but significant increase of CRP levels in the patients. CONCLUSIONS/SIGNIFICANCE: MCP-1, EGF and VEGF may not be suitable markers of prolonged psychosocial stress as previously suggested. Furthermore, significant differences were obtained when using two different protein assays measuring the same samples, indicating that comparing studies where different analytic techniques have been used might be difficult. Increased levels of CRP indicate that low-grade inflammation might be present in patients with exhaustion due to prolonged stress exposure but this inflammation does not seem to be reflected by increase in circulating MCP-1 or other cytokines measured.
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43.
  • Karbalaei, Mardjaneh, et al. (author)
  • Detrusor Induction of miR-132/212 following Bladder Outlet Obstruction: Association with MeCP2 Repression and Cell Viability.
  • 2015
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:1
  • Journal article (peer-reviewed)abstract
    • The microRNAs (miRNAs) miR-132 and miR-212 have been found to regulate synaptic plasticity and cholinergic signaling and recent work has demonstrated roles outside of the CNS, including in smooth muscle. Here, we examined if miR-132 and miR-212 are induced in the urinary bladder following outlet obstruction and whether this correlates with effects on gene expression and cell growth. Three to seven-fold induction of miR-132/212 was found at 10 days of obstruction and this was selective for the detrusor layer. We cross-referenced putative binding sites in the miR-132/212 promoter with transcription factors that were predicted to be active in the obstruction model. This suggested involvement of Creb and Ahr in miR-132/212 induction. Creb phosphorylation (S-133) was not increased, but the number of Ahr positive nuclei increased. Moreover, we found that serum stimulation and protein kinase C activation induced miR-132/212 in human detrusor cells. To identify miR-132/212 targets, we correlated the mRNA levels of validated targets with the miRNA levels. Significant correlations between miR-132/212 and MeCP2, Ep300, Pnkd and Jarid1a were observed, and the protein levels of MeCP2, Pnkd and Ache were reduced after obstruction. Reduction of Ache however closely matched a 90% reduction of synapse density arguing that its repression was unrelated to miR-132/212 induction. Importantly, transfection of antimirs and mimics in cultured detrusor cells increased and decreased, respectively, the number of cells and led to changes in MeCP2 expression. In all, these findings show that obstruction of the urethra increases miR-132 and miR-212 in the detrusor and suggests that this influences gene expression and limits cell growth.
  •  
44.
  • Kierczak, Marcin, 1981-, et al. (author)
  • Contribution of rare whole-genome sequencing variants to plasma protein levels and the missing heritability
  • 2022
  • In: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
  • Journal article (peer-reviewed)abstract
    • Despite the success of genome-wide association studies, much of the genetic contribution to complex traits remains unexplained. Here, we analysed high coverage whole genome sequencing data, to evaluate the contribution of rare genetic variants to 414 plasma proteins. The frequency distribution of genetic variants was skewed towards the rare spectrum, and damaging variants were more often rare. We estimated that less than 4.3% of the narrow-sense heritability is expected to be explained by rare variants in our cohort. Using a gene-based approach, we identified Cis-associations for 237 of the proteins, which is slightly more compared to a GWAS (N=213), and we identified 34 loci in Trans. Several associations were driven by rare variants, and rare variants had on average larger phenotypic effects. We conclude therefore that rare variants could be of  importance for precision medicine applications, but have a more limited contribution to the missing heritability of complex diseases.
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45.
  • Kinch, Amelie, et al. (author)
  • A population-based study of 135 lymphomas after solid organ transplantation : The role of Epstein-Barr virus, hepatitis C and diffuse large B-cell lymphoma subtype in clinical presentation and survival.
  • 2014
  • In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 53:5, s. 669-679
  • Journal article (peer-reviewed)abstract
    • Background. Epstein-Barr virus (EBV) plays a major role in the development of post-transplant lymphoproliferative disorder (PTLD), but there is an increasing awareness of EBV-negative PTLD. The clinical presentation of EBV-negative PTLD has not been as well characterised as EBV-positive cases. Further, there is limited knowledge on the clinical importance of diffuse large B-cell lymphoma (DLBCL) cell of origin subtype post-transplant. Materials and methods. We studied the role of EBV, hepatitis C (HCV) and DLBCL subtype in clinical presentation and survival in 135 post-transplant lymphomas diagnosed 1980-2006 in a population-based cohort of 10 010 Swedish solid organ transplant recipients. The lymphomas were re-evaluated according to WHO 2008, examined for EBV, and clinical data were collected from medical records. Results. Lymphoma incidence rate was 159/100 000 person-years and is also reported by lymphoma subtype. EBV-negative lymphomas constituted 48% and were associated with HCV infection (p = 0.02), bone marrow involvement (p < 0.001), and T-cell phenotype (p = 0.002). Among DLBCL, 78% were of non-germinal centre subtype, which was associated with EBV-positivity (69%, p = 0.001), early occurrence (p = 0.03), heart/liver/lung/pancreas recipients (p = 0.02), anti-T-cell globulin (p = 0.001), and tacrolimus treatment (p = 0.02). DLBCL subtypes had similar overall survival. Five-year overall survival was 42% in all treated patients. Independent poor prognostic factors were older age, B symptoms, ECOG 2-4, kidney/pancreas/heart recipients, T-cell lymphoma, and HCV-infection. Conclusions. With long follow-up, a large part of PTLD is EBV-negative, due to a high proportion of T-cell lymphomas and low of polymorphic PTLD. EBV-negative PTLD have a different clinical presentation. HCV may play an aetiological role in late-onset PTLD and was revealed as a new prognostic factor for inferior survival that needs to be confirmed in larger studies. The heavier immunosuppression in non-kidney transplantations seems to play a role in the development of non-germinal centre DLBCL. DLBCL cell of origin subtype lacks prognostic importance in the transplant setting.
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46.
  • Leijon, Matti, et al. (author)
  • Improvement of physical activity by a kiosk-based electronic screening and brief intervention in routine primary health care : Patient-initiated versus staff-referred
  • 2011
  • In: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 13:4, s. e99-
  • Journal article (peer-reviewed)abstract
    • Background: Interactive behavior change technology (eg, computer programs, Internet websites, and mobile phones) may facilitate the implementation of lifestyle behavior interventions in routine primary health care. Effective, fully automated solutions not involving primary health care staff may offer low-cost support for behavior change. Objectives: We explored the effectiveness of an electronic screening and brief intervention (e-SBI) deployed through a stand-alone information kiosk for promoting physical activity among sedentary patients in routine primary health care. We further tested whether its effectiveness differed between patients performing the e-SBI on their own initiative and those referred to it by primary health care staff. Methods: The e-SBI screens for the physical activity level, motivation to change, attitudes toward performing the test, and physical characteristics and provides tailored feedback supporting behavior change. A total of 7863 patients performed the e-SBI from 2007 through 2009 in routine primary health care in Östergötland County, Sweden. Of these, 2509 were considered not sufficiently physically active, and 311 of these 2509 patients agreed to participate in an optional 3-month follow-up. These 311 patients were included in the analysis and were further divided into two groups based on whether the e-SBI was performed on the patient's own initiative (informed by posters in the waiting room) or if the patient was referred to it by staff. A physical activity score representing the number of days being physically active was compared between baseline e-SBI and the 3-month follow-up. Based on physical activity recommendations, a score of 5 was considered the cutoff for being sufficiently physically active. Results: In all, 137 of 311 patients (44%) were sufficiently physically active at the 3-month follow-up. The proportion becoming sufficiently physically active was 16/55 (29%), 40/101 (40%), and 81/155 (52%) for patients with a physical activity score at baseline of 0, 1 to 2, and 3 to 4, respectively. The patient-initiated group and staff-referred group had similar mean physical activity scores at baseline (2.1, 95% confidence interval [CI] 1.8-2.3, versus 2.3, 95% CI 2.1-2.5) and at follow-up, (4.1, 95% CI 3.4-4.7, vs 4.2, 95% CI 3.7-4.8). Conclusions: Among the sedentary patients in primary health care who participated in the follow-up, the e-SBI appeared effective at promoting short-term improvement of physical activity for about half of them. The results were similar when the e-SBI was patient-initiated or staff-referred. The e-SBI may be a low-cost complement to lifestyle behavior interventions in routine primary health care and could work as a stand-alone technique not requiring the involvment of primary health care staff. © Matti Leijon, Daniel Arvidsson, Per Nilsen, Diana Stark Ekman, Siw Carlfjord, Agneta Andersson, Anne Lie Johansson, Preben Bendtsen.
  •  
47.
  • Mucci, Philip J., et al. (author)
  • PerfMiner : Cluster-wide collection, storage and presentation of application level hardware performance data
  • 2005
  • In: EURO-PAR 2005 PARALLEL PROCESSING, PROCEEDINGS. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 3540287000 ; , s. 124-133
  • Conference paper (peer-reviewed)abstract
    • We present PerfMiner, a system for the transparent collection, storage and presentation of thread-level hardware performance data across an entire cluster. Every sub-process/thread spawned by the user through the batch system is measured with near zero overhead and no dilation of run-time. Performance metrics are collected at the thread level using tool built on top of the Performance Application Programming Interface (PAPI). As the hardware counters are virtualized by the OS, the resulting counts are largely unaffected by other kernel or user processes. PerfMiner correlates this performance data with metadata from the batch system and places it in a database. Through a command line and web interface, the user can make queries to the database to report information on everything from overall workload characterization and system utilization to the performance of a single thread in a specific application. This is in contrast to other monitoring systems that report aggregate system-wide metrics sampled over a period of time. In this paper, we describe our implementation of PerfMiner as well as present some results from the test deployment of PerfMiner across three different clusters at the Center for Parallel Computers at The Royal Institute of Technology in Stockholm, Sweden.
  •  
48.
  • Nordgren, Daniel, et al. (author)
  • Studies of heat transfer and furnace temperature uniformity during combustion of oil and wood using oxygen enrichment technology
  • 2011
  • In: Swedish-Finnish Flame Days 2011.
  • Conference paper (other academic/artistic)abstract
    • In many combustion applications a switch from fossil to renewable fuels, e.g. from fueloil to wood powder, may result in a reduction of production capacity in the boiler,furnace or kiln. Oxygen enrichment of the combustion air can be used to improve thethermal efficiency of practical combustors, i.e. reduce heat losses and promote fuelsavings. In addition, oxygen enrichment can reduce NOx emissions and also facilitateCO2 scrubbing and capture processes in such systems. In this work, flame characteristicsand furnace temperature profiles during oxygen enriched combustion were studied whenoxygen was added to the combustor at different enrichment levels by the use of a lance.The experiments were carried out in a pilot-scale furnace fired with (i) wood powder and(ii) heavy fuel oil (no.5). The results show that for the wood flame, the average furnacetemperature becomes higher and the furnace temperature profile becomes more flat.Thus, compared to conventional air combustion, there are smaller differences betweennear-burner and back-end temperatures as oxygen is added to the process. For the oilflame, as oxygen was added to the process, a higher average furnace temperature wasobserved along with a distinct shift in furnace peak temperature towards the central partsof the furnace, creating a relatively strong temperature gradient towards the back-end ofthe furnace. Comparing the two flames, the furnace temperature profile of the oxygenenriched wood flame becomes more flat compared to the oxygen enriched oil flame. Thisis interpreted as an effect of differences in overall fuel reactivity, in which the oil, being aliquid fuel, ignites and burns faster than the solid fuel wood powder. The results found inthis work shows that the burner that was used, being designed for conventional aircombustion by feeding of air through the primary, secondary and tertiary air vanes, couldhandle the changes in aerodynamics caused by the reduced air flows. The general resultsfrom this work are useful for furnace and kiln applications in which a more controllableflame and process temperature is required, e.g. in a lime kiln where a fuel switch fromfossil fuels to biomass is considered.
  •  
49.
  •  
50.
  • Papakokkinou, Eleni, et al. (author)
  • Excess Morbidity Persists in Patients With Cushing’s Disease During Long-term Remission : A Swedish Nationwide Study
  • 2020
  • In: Journal of Clinical Endocrinology and Metabolism. - Washington : Oxford University Press. - 0021-972X .- 1945-7197. ; 105:8, s. 2616-2624
  • Journal article (peer-reviewed)abstract
    • Context: Whether multisystem morbidity in Cushing's disease (CD) remains elevated during long-term remission is still undetermined.Objective: To investigate comorbidities in patients with CD.Design, setting, and patients: A retrospective, nationwide study of patients with CD identified in the Swedish National Patient Register between 1987 and 2013. Individual medical records were reviewed to verify diagnosis and remission status.Main outcomes: Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by using the Swedish general population as reference. Comorbidities were investigated during three different time periods: (i) during the 3 years before diagnosis, (ii) from diagnosis to 1 year after remission, and (iii) during long-term remission.Results: We included 502 patients with confirmed CD, of whom 419 were in remission for a median of 10 (interquartile range 4 to 21) years. SIRs (95% CI) for myocardial infarction (4.4; 1.2 to 11.4), fractures (4.9; 2.7 to 8.3), and deep vein thrombosis (13.8; 3.8 to 35.3) were increased during the 3-year period before diagnosis. From diagnosis until 1 year after remission, SIRs (95% CI were increased for thromboembolism (18.3; 7.9 to 36.0), stroke (4.9; 1.3 to 12.5), and sepsis (13.6; 3.7 to 34.8). SIRs for thromboembolism (4.9; 2.6 to 8.4), stroke (3.1; 1.8 to 4.9), and sepsis (6.0; 3.1 to 10.6) remained increased during long-term remission.Conclusion: Patients with CD have an increased incidence of stroke, thromboembolism, and sepsis even after remission, emphasizing the importance of early identification and management of risk factors for these comorbidities during long-term follow-up.
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