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1.
  • Artigas Soler, María, et al. (författare)
  • Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
  • 2011
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
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  • Brauer, H.E., et al. (författare)
  • Na intercalation of VSe2 studied by photoemission and scanning tunneling microscopy
  • 1997
  • Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 55:15, s. 10022-10026
  • Tidskriftsartikel (refereegranskat)abstract
    • In situ Na intercalation of the layered compound VSe2 has been studied with photoemission and scanning tunneling microscopy. Core-level spectroscopy proves that Na deposited in UHV onto the VSe2 surface rapidly intercalates, leaving only small amounts at the surface. The scanning tunneling microscopy measurements show that the intercalated Na is not uniformly distributed between the VSe2 layers, but preferentially in two-dimensional islands. Thus the surface region is divided into intercalated and nonintercalated areas. Hole-like features in the intercalated areas are interpreted as locally missing Na.
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  • Repapi, Emmanouela, et al. (författare)
  • Genome-wide association study identifies five loci associated with lung function.
  • 2010
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:1, s. 36-44
  • Tidskriftsartikel (refereegranskat)abstract
    • Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.
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  • Terzidis, Emmanouil, 1994, et al. (författare)
  • Tumor volume definitions in head and neck squamous cell carcinoma - Comparing PET/MRI and histopathology
  • 2023
  • Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140. ; 180
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: In cancer treatment precise definition of the tumor volume is essential, but despite development in imaging modalities, this remains a challenge. Here, pathological tumor volumes from the surgical specimens were obtained and compared to tumor volumes defined from modern PET/ MRI hybrid imaging. The purpose is to evaluate mismatch between the volumes defined from imaging and pathology was estimated and potential clinical impact.Methods and Materials: Twenty-five patients with head and neck squamous cell carcinoma were scanned on an integrated PET/MRI system prior to surgery. Three gross tumor volumes (GTVs) from the primary tumor site were delineated defined from MRI (GTVMRI), PET (GTVPET) and one by utilizing both anatomical images and clinical information (GTVONCO). Twenty-five primary tumor specimens were extracted en bloc, scanned with PET/MRI and co-registered to the patient images. Each specimen was sectioned in blocks, sliced and stained with haematoxylin and eosin. All slices were digitalized and tumor delineated by a head and neck pathologist. The pathological tumor areas in all slices were interpolated yielding a pathological 3D tumor volume (GTVPATO). GTVPATO was compared with the imaging GTV's and potential mismatch was estimated.Results: Thirteen patients were included. The mean volume of GTVONCO was larger than the GTV's defined from PET or MRI. The mean mismatch of the GTVPATO compared to the GTVPET, GTVMRI and GTVONCO was 31.9 %, 54.5 % and 27.9 % respectively, and the entire GTVPATO was only fully encompassed in GTVONCO in 1 of 13 patients. However, after the addition of a clinical 5 mm margin the GTVPATO was fully encompassed in GTVONCO in 11 out of 13 patients.Conclusions: Despite modern hybrid imaging modalities, a mismatch between imaging and pathological defined tumor volumes was observed in all patients. A 5 mm clinical margin was sufficient to ensure inclusion of the entire pathological volume in 11 out of 13 patients.(c) 2023 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 180 (2023) 1-8 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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  • Hallander, H, et al. (författare)
  • [New pertussis vaccines are tested].
  • 1992
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 89:45, s. 3820-2, 3825
  • Tidskriftsartikel (refereegranskat)
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  • Horvath, I., et al. (författare)
  • A European Respiratory Society technical standard: exhaled biomarkers in lung disease
  • 2017
  • Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 49:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Breath tests cover the fraction of nitric oxide in expired gas (FeNO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for FeNO, official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and FeNO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management. Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members. Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised. Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice.
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  • Hu, Q H, et al. (författare)
  • Properties of Tl-2201 thin films
  • 1997
  • Ingår i: Physica. C, Superconductivity. - 0921-4534 .- 1873-2143. ; 282-287:Part 2, s. 1075-1076
  • Tidskriftsartikel (refereegranskat)abstract
    • Tl2Ba2CuO6 (Tl-2201) thin films were synthesised on single crystal LaAlO3 and SrTiO3 substrates and on bicrystal LaAlO3 by an ex-situ process. Depending on thallium content and processing conditions, the films were orthorhombic or tetragonal. Tc was in the range 30 – 92 K while Jc reached 4.106A/cm2 at 12 K. By oxygen depletion, Tc was increased by 15 – 20 K for some films.
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  • Laursen, K. R., et al. (författare)
  • An RCT of acute health effects in COPD-patients after passive vape exposure from e-cigarettes
  • 2021
  • Ingår i: European Clinical Respiratory Journal. - : Informa UK Limited. - 2001-8525. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: E-cigarette use has been shown to have short-term acute effects among active users but less is known of the acute passive effects, particularly among individuals with existing respiratory diseases. Objective: To investigate local and systemic effects of short-term passive vape exposure among patients with mild or moderate chronic obstructive pulmonary disease (COPD). Methods: In a double-blinded crossover study 16 non-smoking COPD-patients (mean age 68) were randomly exposed for 4 h to passive vape (median PM2.5: 18 mu g/m(3) (range: 8-333)) and clean air (PM2.5 < 6 mu g/m(3)) separated by 14 days. Particles were measured using an ultrafine particle counter (P-TRAK) and a scanning mobility particle sizer (SMPS). Health effects including Surfactant Protein-A (SP-A) and albumin in exhaled air, spirometry, FeNO, and plasma proteins were evaluated before, right after, and 24 hours after exposure. Participants reported symptoms throughout exposure sessions. Data were analyzed using mixed models. Results: SP-A in exhaled air was negatively affected by exposure to vape and several plasma proteins increased significantly. Throat irritation was more pronounced during passive vape exposure, while FVC and FEV1 decreased, however, not significantly. Conclusions: SP-A in exhaled air and some plasma proteins were affected by passive vape in patients with COPD indicating inflammation, showing that passive vape exposure is potentially harmful.
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  • Lofstedt, H., et al. (författare)
  • Respiratory and Ocular Symptoms Among Employees at Swedish Indoor Swimming Pools
  • 2016
  • Ingår i: Journal of Occupational and Environmental Medicine. - : Ovid Technologies (Wolters Kluwer Health). - 1076-2752. ; 58:12, s. 1190-1195
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:This study investigated trichloramine exposure and prevalence of respiratory and ocular symptoms among Swedish indoor swimming pool workers.Methods:Questionnaires were distributed to pool workers and referents. Lung function and fraction of exhaled nitric oxide (FeNO) were measured before and after work. Exposure to trichloramine and trihalomethanes was measured over work shifts.Results:The mean personal trichloramine exposure was 36g/m(3). Significantly more exposed workers reported ocular and nasal symptoms. There were significant differences between groups in FeNO change following work, with exposed showing increased FeNO, which grew when analyses included only nonsmokers.Conclusions:The findings indicate that indoor swimming pool environments may have irritating effects on mucous membranes. FeNO data also indicate an inflammatory effect on central airways, but the clinical relevance is unclear. Low trichloramine levels found in this study were not associated with health effects.
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  • Amole, C., et al. (författare)
  • Resonant quantum transitions in trapped antihydrogen atoms
  • 2012
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 483:7390, s. 439-U86
  • Tidskriftsartikel (refereegranskat)abstract
    • The hydrogen atom is one of the most important and influential model systems in modern physics. Attempts to understand its spectrum are inextricably linked to the early history and development of quantum mechanics. The hydrogen atom's stature lies in its simplicity and in the accuracy with which its spectrum can be measured(1) and compared to theory. Today its spectrum remains a valuable tool for determining the values of fundamental constants and for challenging the limits of modern physics, including the validity of quantum electrodynamics and-by comparison with measurements on its antimatter counterpart, antihydrogen-the validity of CPT (charge conjugation, parity and time reversal) symmetry. Here we report spectroscopy of a pure antimatter atom, demonstrating resonant quantum transitions in antihydrogen. We have manipulated the internal spin state(2,3) of antihydrogen atoms so as to induce magnetic resonance transitions between hyperfine levels of the positronic ground state. We used resonant microwave radiation to flip the spin of the positron in antihydrogen atoms that were magnetically trapped(4-6) in the ALPHA apparatus. The spin flip causes trapped anti-atoms to be ejected from the trap. We look for evidence of resonant interaction by comparing the survival rate of trapped atoms irradiated with microwaves on-resonance to that of atoms subjected to microwaves that are off-resonance. In one variant of the experiment, we detect 23 atoms that survive in 110 trapping attempts with microwaves off-resonance (0.21 per attempt), and only two atoms that survive in 103 attempts with microwaves on-resonance (0.02 per attempt). We also describe the direct detection of the annihilation of antihydrogen atoms ejected by the microwaves.
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  • Barnes, H., et al. (författare)
  • Occupation versus environmental factors in hypersensitivity pneumonitis: population attributable fraction
  • 2020
  • Ingår i: Erj Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 6:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Despite well-documented case series of hypersensitivity pneumonitis (HP), epidemiological data delineating relative contributions of risk factors are sparse. To address this, we estimated HP risk in a case-referent study of occupational and nonoccupational exposures. Methods: We recruited cases of HP by ICD-9 codes from an integrated healthcare delivery system (IHCDS) and a tertiary medical care centre. We drew referents, matched for age and sex, from the IHCDS. Participants underwent comprehensive, structured telephone interviews eliciting details of occupational and home environmental exposures. We employed a hierarchical analytic approach for data reduction based on the false discovery rate method within clusters of exposures. We measured lung function and selected biomarkers in a subset of participants. We used multivariate logistic regression to estimate exposure-associated odds ratios (ORs) and population attributable fractions (PAFs) for HP. Results: We analysed data for 192 HP cases (148 IHCDS; 44 tertiary care) and 229 referents. Occupational exposures combined more than doubled the odds of developing HP (OR 2.67; 95% CI 1.73-4.14) with a PAF of 34% (95% CI 21-46%); nonoccupational bird exposure also doubled the HP odds (OR 2.02; 95% CI 1.13-3.60), with a PAF of 12% (3-21%). Lung function and selected biomarkers did not substantively modify the risk estimates on the basis of questionnaire data alone. Discussion: In a case-referent approach evaluating HP risk, identifiable exposures accounted, on an epidemiological basis, for approximately two in three cases of disease; conversely, for one in three, the risk factors for disease remained elusive.
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  • Bonaca, M. P., et al. (författare)
  • Vorapaxar in Patients With Peripheral Artery Disease Results From TRA2 degrees P-TIMI 50
  • 2013
  • Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 127:14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background—Vorapaxar is a novel antagonist of protease-activated receptor-1, the primary receptor for thrombin on human platelets that is also present on vascular endothelium and smooth muscle. Patients with peripheral artery disease are at risk of systemic atherothrombotic events, as well as acute and chronic limb ischemia and the need for peripheral revascularization. Methods and Results—The Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Atherosclerosis (TRA2°P-TIMI 50) was a randomized, double-blind, placebo-controlled trial of vorapaxar in 26 449 patients with stable atherosclerotic vascular disease (myocardial infarction, stroke, or peripheral artery disease). Patients with qualifying peripheral artery disease (n=3787) had a history of claudication and an ankle-brachial index of <0.85 or prior revascularization for limb ischemia. The primary efficacy end point was cardiovascular death, myocardial infarction, or stroke, and the principal safety end point was Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) bleeding. In the peripheral artery disease cohort, the primary end point did not differ significantly with vorapaxar (11.3% versus 11.9%; hazard ratio, 0.94; 95% confidence interval, 0.78–1.14; P=0.53). However, rates of hospitalization for acute limb ischemia (2.3% versus 3.9%; hazard ratio, 0.58; 95% confidence interval, 0.39–0.86; P=0.006) and peripheral artery revascularization (18.4% versus 22.2%; hazard ratio, 0.84; 95% confidence interval, 0.73–0.97; P=0.017) were significantly lower in patients randomized to vorapaxar. Bleeding occurred more frequently with vorapaxar compared with placebo (7.4% versus 4.5%; hazard ratio, 1.62; 95% confidence interval, 1.21–2.18; P=0.001). Conclusions—Vorapaxar did not reduce the risk of cardiovascular death, myocardial infarction, or stroke in patients with peripheral artery disease; however, vorapaxar significantly reduced acute limb ischemia and peripheral revascularization. The beneficial effects of protease-activated receptor-1 antagonism on limb vascular events were accompanied by an increased risk of bleeding.
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  • Carlsson, Rose-Marie, et al. (författare)
  • Two consecutive randomized controlled pertussis booster trials in children initially vaccinated in infancy with an acellular vaccine: The first with a five-component Tdap vaccine to 5-year olds and the second with five- or monocomponent Tdap vaccines at age 14-15 years
  • 2015
  • Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 33:31, s. 3717-3725
  • Tidskriftsartikel (refereegranskat)abstract
    • Prior study children from a DTaP efficacy trial were recruited at ages 5 and 15 years to randomized booster trials addressing immunogenicity and reactogenicity; 475 preschool children received mixed or separate injections of a reduced antigen vaccine (Tdap5, Sanofi Pasteur MSD) and an inactivated polio vaccine, and 230 adolescents received the same or another booster vaccine (Tdap1, SSI, Denmark). Pre-vaccination antibody concentrations against pertussis antigens were significantly higher at 15 than 5 years of age, probably due to natural boosting between the studies. Tdap5 induced comparable anti-PT concentrations at both ages, but antibody responses were significantly higher to filamentous haemagglutinin, pertactin and fimbriae 2/3 in adolescents. As expected, a higher amount of PT (Tdap1, 20 mu g) induced a stronger anti-PT response than a lower amount (Tdap5, 2.5 mu g). The frequency of adverse events was low and there were no serious adverse reactions. All local reactions had an early onset and a short duration. A large swelling or redness of more than half of the upper arm circumference was reported in 8/475 5-year-olds and in 6/230 15-year-olds. Children vaccinated with Tdap5 reported more moderate pain in adolescence than at preschool age, whereas itching was only reported in preschool children. Sweden introduced DTaP vaccines in 1996 after a 17-year hiatus with no general pertussis vaccination and pertussis was still endemic at the time of the studies. The frequency of adverse events was nevertheless low in both preschool children and adolescents and antibody responses were adequate. These studies document immunogenicity and reactogenicity in a trial cohort consecutively vaccinated with acellular pertussis vaccines from infancy to adolescence. (C) 2015 Elsevier Ltd. All rights reserved.
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  • Ghaderi, A, et al. (författare)
  • A ROR1 Small Molecule Inhibitor (KAN0441571C) Induced Significant Apoptosis of Mantle Cell Lymphoma (MCL) Cells
  • 2022
  • Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 14:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The receptor tyrosine kinase orphan receptor 1 (ROR1) is absent in most normal adult tissues but overexpressed in various malignancies and is of importance for tumor cell survival, proliferation, and metastasis. In this study, we evaluated the apoptotic effects of a novel small molecule inhibitor of ROR1 (KAN0441571C) as well as venetoclax (BCL-2 inhibitor), bendamustine, idelalisib (PI3Kδ inhibitor), everolimus (mTOR inhibitor), and ibrutinib (BTK inhibitor) alone or in combination in human MCL primary cells and cell lines. ROR1 expression was evaluated by flow cytometry and Western blot (WB). Cytotoxicity was analyzed by MTT and apoptosis by Annexin V/PI staining as well as signaling and apoptotic proteins (WB). ROR1 was expressed both in patient-derived MCL cells and human MCL cell lines. KAN0441571C alone induced significant time- and dose-dependent apoptosis of MCL cells. Apoptosis was accompanied by decreased expression of MCL-1 and BCL-2 and cleavage of PARP and caspase 3. ROR1 was dephosphorylated as well as ROR1-associated signaling pathway molecules, including the non-canonical WNT signaling pathway (PI3Kδ/AKT/mTOR). The combination of KAN0441571C and ibrutinib, venetoclax, idelalisib, everolimus, or bendamustine had a synergistic apoptotic effect and significantly prevented phosphorylation of ROR1-associated signaling molecules as compared to KAN0441571C alone. Our results suggest that targeting ROR1 by a small molecule inhibitor, KAN0441571C, should be further evaluated particularly in combination with other targeting drugs as a new therapeutic approach for MCL.
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  • Ghaderi, A, et al. (författare)
  • ROR1 Is Expressed in Diffuse Large B-Cell Lymphoma (DLBCL) and a Small Molecule Inhibitor of ROR1 (KAN0441571C) Induced Apoptosis of Lymphoma Cells
  • 2020
  • Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 8:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The receptor tyrosine kinase ROR1 is absent in most normal adult tissues, but overexpressed in several malignancies. In this study, we explored clinical and functional inhibitory aspects of ROR1 in diffuse large B-cell lymphoma (DLBCL). ROR1 expression in tumor cells was more often observed in primary refractory DLBCL, Richter’s syndrome and transformed follicular lymphoma than in relapsed and non-relapsed DLBCL patients (p < 0.001). A survival effect of ROR1 expression was preliminarily observed in relapsed/refractory patients independent of gender and stage but not of age, cell of origin and international prognostic index. A second generation small molecule ROR1 inhibitor (KAN0441571C) induced apoptosis of ROR1+ DLBCL cell lines, similar to venetoclax (BCL-2 inhibitor) but superior to ibrutinib (BTK inhibitor). The combination of KAN0441571C and venetoclax at EC50 concentrations induced almost complete killing of DLBCL cell lines. Apoptosis was accompanied by the downregulation of BCL-2 and MCL-1 and confirmed by the cleavage of PARP and caspases 3, 8, 9. PI3Kδ/AKT/mTOR (non-canonical Wnt pathway) as well as β-catenin and CK1δ (canonical pathway) were inactivated. In zebra fishes transplanted with a ROR1+ DLBCL cell line, KAN0441571C induced a significant tumor reduction. New drugs with mechanisms of action other than those available for DLBCL are warranted. ROR1 inhibitors might represent a novel promising approach.
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  • Hallgren, C., et al. (författare)
  • Validating a Simplified Lung Ultrasound Protocol for Detection and Quantification of Pulmonary Edema in Patients With Chronic Kidney Disease Receiving Maintenance Hemodialysis
  • 2023
  • Ingår i: Journal of Ultrasound in Medicine. - : Wiley. - 0278-4297 .- 1550-9613. ; 42:9, s. 2013-2021
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Pulmonary edema is a common clinical problem and lung ultrasound (LUS) presents an efficient method for evaluating this pathology. This study aims to investigate if a clinically efficient LUS protocol can quantify the level of extravascular lung fluid in patients receiving hemodialysis, and to develop a simplified B-line scoring system based on this protocol.Methods A simple 8-area LUS approach was used for the assessment of the extravascular fluid status in patients before, during, and after receiving hemodialysis. The LUS assessments were compared to the amount of removed fluid over time. To determine the best B-line score system, different scorings for each zone were tested in a linear mixed model with pseudo R-square model fit against removed fluid. The B-line score was further validated through correlations with changes in oxygen saturation, grade of dyspnea, and body weight over time.Results A total of 53 patients were included and examined on 108 hemodialysis occasions. Median fluid removal was 2.3 L. The B-line score model with best fit was a score of 0 points in a zone with 0 or 1 B-lines, 1 point with 2 or 3 B-lines, 2 points with 3 or more B-lines, and 3 points with any interstitial confluence. Using this B-line score, we found a significant association with amount of removed fluid, oxygen saturation, grade of dyspnea, and change in body weight.Conclusion A straightforward protocol for LUS and B-line score system was shown valid for quantification of pulmonary edema and fluid removal in hemodialysis patients. The scoring system developed here can be useful also in other patient groups, but this requires further validation.
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  • Horvath, I., et al. (författare)
  • Exhaled breath condensate: methodological recommendations and unresolved questions
  • 2005
  • Ingår i: Eur Respir J. ; 26:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Collection of exhaled breath condensate (EBC) is a noninvasive method for obtaining samples from the lungs. EBC contains large number of mediators including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, nitrogen oxides, peptides and cytokines. Concentrations of these mediators are influenced by lung diseases and modulated by therapeutic interventions. Similarly EBC pH also changes in respiratory diseases. The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required. Based on the currently available evidence and the consensus of the expert panel for EBC collection, the following general recommendations were put together for oral sample collection: collect during tidal breathing using a noseclip and a saliva trap; define cooling temperature and collection time (10 min is generally sufficient to obtain 1-2 mL of sample and well tolerated by patients); use inert material for condenser; do not use resistor and do not use filter between the subject and the condenser. These are only general recommendations and certain circumstances may dictate variation from them. Important areas for future research involve: ascertaining mechanisms and site of exhaled breath condensate particle formation; determination of dilution markers; improving reproducibility; employment of EBC in longitudinal studies; and determining the utility of exhaled breath condensate measures for the management of individual patients. These studies are required before recommending this technique for use in clinical practice.
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  • Jansen, Willemijn J, et al. (författare)
  • Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
  • 2022
  • Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
  • Tidskriftsartikel (refereegranskat)abstract
    • One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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49.
  • Kampmann, Tobias Christoph, 1987-, et al. (författare)
  • Syn-tectonic sulphide remobilization and trace element redistribution at the Falun pyritic Zn-Pb-Cu-(Au-Ag) sulphide deposit, Bergslagen, Sweden
  • 2018
  • Ingår i: Ore Geology Reviews. - : Elsevier. - 0169-1368 .- 1872-7360. ; 96, s. 48-71
  • Tidskriftsartikel (refereegranskat)abstract
    • Mineralization types at the Palaeoproterozoic Falun base metal sulphide deposit are predominantly pyritic Zn-Pb-Cu-rich massive sulphide mineralization, disseminated to semi-massive Cu-Au mineralization, auriferous quartz veins, and mineralized shear zones of talc-chlorite-dominated schist. The massive and disseminated to semi-massive sulphide mineralization types were subject to polyphase ductile deformation (D1 and D2) and metamorphism under low-P, lower-amphibolite facies conditions, which led to the development of ore textures and paragenetic relationships indicating both mechanical and chemical remobilization of sulphides. In the massive sulphide mineralization, rare inclusion-rich pyrite occurs as relic cores inside inclusion-poor metamorphosed pyrite. Imaging and spot analysis using multielement laser ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS) reveal that inclusion-poor pyrite was depleted in trace elements, which were originally present as non-stoichiometric lattice substitutions or in mineral inclusions. The inclusion-rich pyrite was shielded from depletion and, at least partly, retained its initially higher trace element concentrations, including Au.Gold is also associated with chalcopyrite in the disseminated to semi-massive Cu-Au mineralization and in the system of auriferous quartz veins hosted therein, the latter being also affected by the D2 ductile strain. It is inferred that emplacement of the vein system took place after the peak of metamorphism, which occurred between D1 and D2, but prior to and possibly even shortly after completion of the D2 deformational event. Similarities in trace element signatures in chalcopyrite are compatible with the interpretation that the quartz veins formed by local chemical remobilization of components from the Cu-Au mineralization. Transport of liberated Au from pyrite during grain growth in the massive sulphide mineralization may have upgraded the Au endowment in the quartz veins, leading to the additional formation of native gold in the veins. A strong correspondence between elements liberated from pyrite (e.g. Pb, Bi, Se and Au) and those forming discrete and characteristic mineral phases in the quartz veins (Pb-Bi sulphosalts, native gold) supports this hypothesis.Trace element signatures for the main sulphide minerals pyrite, chalcopyrite, sphalerite and galena are similar to previously published data from other metamorphosed massive sulphide deposits. The association of the Falun mineralization with elevated Bi is reflected by its occurrence in sulphide minerals (e.g. galena) and in abundant mineral inclusions of Pb-Bi sulphosalts (e.g. weibullite), especially in the disseminated to semi-massive Cu-Au mineralization. Elevated Sn concentrations in the lattice and/or as cassiterite inclusions in chalcopyrite, sphalerite and galena are compatible with a hot, acidic and reducing fluid during formation of the syn-volcanic, base metal sulphide mineralization and associated host-rock alteration.
  •  
50.
  • Kim, Y B, et al. (författare)
  • Atomic force microscopy of rubbed polyimide aligning films for liquid crystal displays
  • 1995
  • Ingår i: 15th International Liquid Crystal ConferenceBUDAPEST, HUNGARY, JUL 03-08, 1994. ; , s. 89-98
  • Konferensbidrag (refereegranskat)abstract
    • The surface of polyimide (PI) films for aligning liquid crystals were studied by means of atomic force microscopy (AFM). The surface of the unrubbed PI films consisted of polymer clusters of different sizes which are randomly distributed over the film area. After rubbing, however, these polymer clusters formed long chains along the rubbing direction. The cluster chains were separated with periodicity about 100 nm for weak rubbing strength. Deeper grooves are also present, separated with periodicity about 2 mu m that could be related to the microstructure of the fibres from the rubbing cloth. On increasing the rubbing strength further on, the cluster chains coalesce into wider ones. The rubbed PI films show optical retardation, which was increased rapidly with increased the rubbing strength and reached a constant value of about 1.4nm.
  •  
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