| 1. |
- Dalin, Frida, 1984-, et al.
(författare)
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Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
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| 2. |
- Lizana, Helena, et al.
(författare)
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Whole-Body Biodistribution and Dosimetry of the Dopamine Transporter Radioligand 18F-FE-PE2I in Human Subjects
- 2018
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 59:8, s. 1275-1280
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Tidskriftsartikel (refereegranskat)abstract
- F-18-(E)-N-(3-iodoprop-2-enyl)-2 beta-carbofluoroethoxy-3 beta-(4'-methylphenyl) nortropane (F-18-FE-PE2I) was recently developed and has shown adequate affinity and high selectivity for the dopamine transporter (DAT). Previous studies have shown promising results for F-18-FE-PE2I as a suitable radioligand for DAT imaging. In this study, we investigated the whole-body biodistribution and dosimetry of F-18-FE-PE2I in healthy volunteers to support its utility as a suitable PET imaging agent for the DAT. Methods: Five healthy volunteers were given a mean activity of 2.5 MBq/kg, and 3 PET scans, head to thigh, were performed immediately after injection followed by 4 whole-body PET/CT scans between 0.5 and 6 h after injection. Blood samples were drawn in connection with the whole-body scans, and all urine was collected until 6 h after injection. Volumes of interest were delineated around 17 organs on all images, and the areas under the time-activity curves were calculated to obtain the total number of decays in the organs. The absorbed doses to organs and the effective dose were calculated using the software IDAC. Results: The highest activity concentration was observed in the liver (0.9%-1.2% injected activity/100 g) up to 30 min after injection. At later time points, the highest concentration was seen in the gallbladder (1.1%-0.1% injected activity/100 g). The activity excreted with urine ranged between 23% and 34%, with a mean of 28%. The urinary bladder received the highest absorbed dose (119 mu Gy/MBq), followed by the liver (46 mu Gy/MBq). The effective dose was 23 mu Sv/MBq (range, 19-28 mu Sv/MBq), resulting in an effective dose of 4.6 mSv for an administered activity of 200 MBq. Conclusion: The effective dose is within the same order of magnitude as other commonly used PET imaging agents as well as DAT agents. The reasonable effective dose, together with the previously reported favorable characteristics for DAT imaging and quantification, indicates that F-18-FE-PE2I is a suitable radioligand for DAT imaging.
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| 3. |
- Akner, Gunnar, 1953-, et al.
(författare)
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Vi står gärna bakom en utfallsbaserad vård
- 2017
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Ingår i: Dagens Samhälle. - 1652-6511.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Jörgen Nordenström försöker få det till att vår kritik av värdebaserad vård egentligen handlar om att vi vill ha mer resurser. Han har helt missuppfattat oss, skriver 26 specialistläkare i en replik.
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| 4. |
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| 6. |
- Bagger, Alexander, et al.
(författare)
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Ab Initio Cyclic Voltammetry on Cu(111), Cu(100) and Cu(110) in Acidic, Neutral and Alkaline Solutions
- 2019
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Ingår i: ChemPhysChem. - : Wiley. - 1439-4235 .- 1439-7641. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- Electrochemical reactions depend on the electrochemical interface between the electrode surfaces and the electrolytes. To control and advance electrochemical reactions there is a need to develop realistic simulation models of the electrochemical interface to understand the interface from an atomistic point-of-view. Here we present a method for obtaining thermodynamic realistic interface structures, a procedure we use to derive specific coverages and to obtain ab initio simulated cyclic voltammograms. As a case study, the method and procedure is applied in a matrix study of three Cu facets in three different electrolytes. The results have been validated by direct comparison to experimental cyclic voltammograms. The alkaline (NaOH) cyclic voltammograms are described by H* and OH*, while in neutral medium (KHCO3) the CO3* species are dominating and in acidic (KCl) the Cl* species prevail. An almost one-to-one mapping is observed from simulation to experiments giving an atomistic understanding of the interface structure of the Cu facets. Atomistic understanding of the interface at relevant eletrolyte conditions will further allow realistic modelling of electrochemical reactions of importance for future eletrocatalytic studies.
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| 7. |
- Decker, Ralph, 1968, et al.
(författare)
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GH dose reduction maintains normal prepubertal height velocity after initial catch up growth in short children.
- 2019
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 104:3, s. 835-844
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Tidskriftsartikel (refereegranskat)abstract
- GH responsiveness guides GH dosing during the catch-up growth (CUG) period; however, little is known regarding GH dosing during the prepubertal maintenance treatment period.To evaluate if standard deviation score (SDS) channel parallel growth with normal height velocity can be maintained following CUG by reducing GH dose by 50% in children receiving doses individualized based on estimated GH-responsiveness during the catch-up period.and settings: Prepubertal children (n=98; 72 boys) receiving GH during CUG (GH-deficient (n=33); non-GH-deficient (n=65)), were randomized after 2-3 years to either a 50% reduced individualized (GHRID; n=27; 20 boys) or unchanged individualized dose (GHUID; n=38; 27 boys). Another 33 children (25 boys) continued on a standard weight-based dose, 43 µg/kg/day (GHFIX).The primary endpoint was the proportion of children with ΔheightSDS within ±0.3 at 1 year after GH-dose reduction, versus two control groups: GHUID and GHFIX. The hypothesis was that heightSDS could be maintained within ±0.3 with a reduced individualized GH dose.For the intention-to-treat population at 1 year, 85% of the GHRIDgroup maintained ΔheightSDS within ±0.3 versus 41% in the GHUIDgroup, p=0.0055 and 48% in the GHFIXgroup, p=0.0047. ΔIGF-ISDS in the GHRIDgroup was (mean±SD) -0.75±1.0 at 3 months, p=0.003 and at 1 year -0.72±1.2, compared to the GHUIDgroup 0.15±1.2, p=0.005, and for the GHFIXgroup 0.05±1.0, p=0.02.Channel parallel growth, i.e. normal height velocity, and IGFSDS levels within ±2 were maintained after completed CUG using a 50% lower individualized dose than used during the CUG period.
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| 8. |
- Girons Lopez, Marc, 1986-
(författare)
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Information Needs for Water Resource and Risk Management : Hydro-Meteorological Data Value and Non-Traditional Information
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Data availability is extremely important for water management. Without data it would not be possible to know how much water is available or how often extreme events are likely to occur. The usually available hydro-meteorological data often have a limited representativeness and are affected by errors and uncertainties. Additionally, their collection is resource-intensive and, thus, many areas of the world are severely under-monitored. Other areas are seeing an unprecedented – yet local – wealth of data in the last decades. Additionally, the spread of new technologies together with the integration of different approaches to water management science and practice have uncovered a large amount of soft information that can potentially complement and expand the possibilities of water management.This thesis presents a series of studies that address data opportunities for water management. Firstly, the hydro-meteorological data needs for correctly estimating key processes for water resource management such as precipitation and discharge were evaluated. Secondly, the use of non-traditional sources of information such as social media and human behaviour to improve the efficiency of flood mitigation actions were explored. The results obtained provide guidelines for determining basic hydro-meteorological data needs. For instance, an upper density of 24 rain gauges per 1000 km2 for spatial precipitation estimation beyond which improvements are negligible was found. Additionally, a larger relative value of discharge data respect to precipitation data for calibrating hydrological models was observed. Regarding non-traditional sources of information, social memory of past flooding events was found to be a relevant factor determining the efficiency of flood early warning systems and therefore their damage mitigation potential. Finally, a new methodology to use social media data for probabilistic estimates of flood extent was put forward and shown to achieve results comparable to traditional approaches.This thesis significantly contributes to integrated water management by improving the understanding of data needs and opportunities of new sources of information thus making water management more efficient and useful for society.
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| 9. |
- Haglind, C Bieneck, et al.
(författare)
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Increased and early lipolysis in children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency during fast
- 2015
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Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 38:2, s. 315-322
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Tidskriftsartikel (refereegranskat)abstract
- Children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) have a defect in the degradation of long-chain fatty acids and are at risk of hypoketotic hypoglycemia and insufficient energy production as well as accumulation of toxic fatty acid intermediates. Knowledge on substrate metabolism in children with LCHAD deficiency during fasting is limited. Treatment guidelines differ between centers, both as far as length of fasting periods and need for night feeds are concerned. To increase the understanding of fasting intolerance and improve treatment recommendations, children with LCHAD deficiency were investigated with stable isotope technique, microdialysis, and indirect calometry, in order to assess lipolysis and glucose production during 6 h of fasting. We found an early and increased lipolysis and accumulation of long chain acylcarnitines after 4 h of fasting, albeit no patients developed hypoglycemia. The rate of glycerol production, reflecting lipolysis, averaged 7.7 ± 1.6 µmol/kg/min, which is higher compared to that of peers. The rate of glucose production was normal for age; 19.6 ± 3.4 µmol/kg/min (3.5 ± 0.6 mg/kg/min). Resting energy expenditure was also normal, even though the respiratory quotient was increased indicating mainly glucose oxidation. The results show that lipolysis and accumulation of long chain acylcarnitines occurs before hypoglycemia in fasting children with LCHAD, which may indicate more limited fasting tolerance than previously suggested.
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| 10. |
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| 11. |
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| 13. |
- Reynolds, Eduardo, et al.
(författare)
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Robustness of flood-model calibration using single and multiple events
- 2019
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Ingår i: Hydrological Sciences Journal. - Oxon : Taylor & Francis. - 0262-6667 .- 2150-3435. ; 65:5, s. 842-853
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Tidskriftsartikel (refereegranskat)abstract
- Lack of discharge data for model calibration is challenging for flood prediction in ungauged basins. Since establishment and maintenance of a permanent discharge station is resource demanding, a possible remedy could be to measure discharge only for a few events. We tested the hypothesis that a few flood-event hydrographs in a tropical basin would be sufficient to calibrate a bucket-type rainfall-runoff model, namely the HBV model, and proposed a new event-based calibration method to adequately predict floods. Parameter sets were chosen based on calibration of different scenarios of data availability, and their ability to predict floods was assessed. Compared to not having any discharge data, flood predictions improved already when one event was used for calibration. The results further suggest that two to four events for calibration may considerably improve flood predictions with regard to accuracy and uncertainty reduction, whereas adding more events beyond this resulted in small performance gains.
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| 14. |
- Reynolds, Eduardo, et al.
(författare)
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Sub-daily runoff predictions using parameters calibrated on the basis of data with a daily temporal resolution
- 2017
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Ingår i: Journal of Hydrology. - : Elsevier BV. - 0022-1694 .- 1879-2707. ; 550, s. 399-411
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Tidskriftsartikel (refereegranskat)abstract
- Concentration times in small and medium-sized basins (similar to 10-1000 km(2)) are commonly less than 24 h. Flood-forecasting models are thus required to provide simulations at high temporal resolutions (1 h-6 h), although time-series of input and runoff data with sufficient lengths are often only available at the daily temporal resolution, especially in developing countries. This has led to study the relationships of estimated parameter values at the temporal resolutions where they are needed from the temporal resolutions where they are available. This study presents a methodology to treat empirically model parameter dependencies on the temporal resolution of data in two small basins using a bucket-type hydrological model, HBV-light, and the generalised likelihood uncertainty estimation approach for selecting its parameters. To avoid artefacts due to the numerical resolution or numerical method of the differential equations within the model, the model was consistently run using modelling time steps of one-hour regardless of the temporal resolution of the rainfall-runoff data. The distribution of the parameters calibrated at several temporal resolutions in the two basins did not show model parameter dependencies on the temporal resolution of data and the direct transferability of calibrated parameter sets (e.g., daily) for runoff simulations at other temporal resolutions for which they were not calibrated (e.g., 3 h or 6 h) resulted in a moderate (if any) decrease in model performance, in terms of Nash-Sutcliffe and volume-error efficiencies. The results of this study indicate that if sub-daily forcing data can be secured, flood forecasting in basins with sub-daily concentration times may be possible with model-parameter values calibrated from long time series of daily data. Further studies using more models and basins are required to test the generality of these results.
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| 15. |
- Reynolds, J. Eduardo, et al.
(författare)
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Definitions of climatological and discharge days : do they matter in hydrological modelling?
- 2018
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Ingår i: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; 63:5, s. 836-844
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Tidskriftsartikel (refereegranskat)abstract
- The performance of hydrological models is affected by uncertainty related to observed climatological and discharge data. Although the latter has been widely investigated, the effects on hydrological models from different starting times of the day have received little interest. In this study, observational data from one tropical basin were used to investigate the effects on a typical bucket-type hydrological model, the HBV, when the definitions of the climatological and discharge days are changed. An optimization procedure based on a genetic algorithm was used to assess the effects on model performance. Nash-Sutcliffe efficiencies varied considerably between day definitions, with the largest dependence on the climatological-day definition. The variation was likely caused by how storm water was assigned to one or two daily rainfall values depending on the definition of the climatological day. Hydrological models are unlikely to predict high flows accurately if rainfall intensities are reduced because of the day definition.
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| 16. |
- Reynolds Puga, José Eduardo, 1982-
(författare)
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Flood Prediction in data-scarce basins : Maximising the value of limited hydro-meteorological data
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Floods pose a threat to society that can cause large socio-economic damages and loss of life in many parts of the world. Flood-forecasting models are required to provide simulations at temporal resolutions higher than a day in basins with concentration times smaller than 24 h. However, data at such resolutions are commonly limited or not available, especially in developing or low-income countries. This thesis covers issues related to the scarcity and lack of high temporal-resolution hydro-meteorological data and explores methods where the value of existing data is maximised to improve flood prediction.By varying the starting time of daily records (the day definition), it was shown that this definition had large implications on model calibration and runoff simulation and therefore, should be considered in regionalisation and flood-forecasting applications. A method was developed to treat empirically model-parameter dependencies on the temporal resolution of data. Model parameters seemed to become independent of the temporal resolution of data when the modelling time-step was sufficiently small. Thus, if sub-daily forcing data can be secured, flood forecasting in basins with sub-daily concentration times may be possible using model-parameter values calibrated from time series of daily data. A new calibration method using only a few event hydrographs could improve flood prediction compared to a scenario with no discharge data. Two event hydrographs may be sufficient for calibration, but accuracy and reduction in uncertainty may improve if data on more events can be acquired. Using flood events above a threshold with a high frequency of occurrence for calibration may be as useful for flood prediction as using only extreme events with a low frequency of occurrence. The accuracy of the rainfall forecasts strongly influenced the predictive performance of a flood model calibrated with limited discharge data. Between volume and duration errors of the rainfall forecast, the former had the larger impact on model performance.The methods previously described proved to be useful for predicting floods and are expected to support flood-risk assessment and decision making during the occurrence of floods in data-scarce regions. Further studies using more models and basins are required to test the generality of these results.
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| 17. |
- Soldemo, Markus, et al.
(författare)
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Interaction of sulfur dioxide and near-ambient pressures of water vapor with cuprous oxide surfaces
- 2017
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 121:43, s. 24011-24024
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Tidskriftsartikel (refereegranskat)abstract
- The interaction of water vapor and sulfur dioxide (SO2) with single crystal cuprous oxide (Cu2O) surfaces of (100) and (111) termination was studied by photoelectron spectroscopy (PES) and density functional theory (DFT). Exposure to near-ambient pressures of water vapor, at 5 × 10-3 %RH and 293 K, hydroxylates both Cu2O surfaces with OH coverage up to 0.38 copper monolayers (ML) for (100) and 0.25 ML for (111). O 1s surface core level shifts indicate that the hydroxylation lifts the (3,0;1,1) reconstruction of the clean (100) surface. On both clean Cu2O terminations, SO2 adsorbs to unsaturated surface oxygen atoms to form SO3 species with coverage, after a saturating SO2 dose, corresponding to 0.20 ML on the Cu2O(100) surface and 0.09 ML for the Cu2O(111) surface. Our combined DFT and PES results suggest that the SO2 to SO3 transformation is largely facilitated by unsaturated copper atoms at the Cu2O(111) surface. SO3-terminated surfaces exposed to low doses of water vapor (=100 langmuirs) in ultrahigh vacuum show no adsorption or reaction. However, during exposure to near-ambient pressures of water vapor, the SO3 species dissociate, and sulfur replaces a Cu2O lattice oxygen in a reaction that forms Cu2S. The hydroxylation of the Cu2O surfaces is believed to play a central role in the reaction.
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| 18. |
- Stepanov, Vladimir, et al.
(författare)
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Development of [C-11]/[H-3-1]THK-5351-A potential novel carbon-11 tau imaging PET radioligand
- 2017
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Ingår i: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 46, s. 50-53
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Due to the rise in the number of patients with dementia the imperative for finding new diagnostic and treatment options becomes ever more pressing. While significant progress has been made in PET imaging of A beta aggregates both in vitro and in vivo, options for imaging tau protein aggregates selectively are still limited. Based on the work previously published by researchers from the Tohoku University, Japan, that resulted in the development of [F-18]THK-5351, we have undertaken an effort to develop a carbon-11 version of the identical structure - [C-11]THK-5351. In parallel, THK-5351 was also labeled with tritium ([H-3]THK-5351) for use in in vitro autoradiography (ARG). Methods: The carbon -11 labeling was performed starting with di-protected enantiomeric pure precursor-tertbutyl 5-(6-( (2S)-3-fluoro-2-(tetrahydro-2H-Pyran-2-yloxy)proPoxy)quinolin-2-yl)pyridin-2-yl carbamate, which was reacted with [C-11]MeI, using DMF as the solvent and NaH as base, followed by deprotection with trifluoroacetic acid/water mixture, resulting in enantiomerically pure carbon-11 radioligand,[C-11]THK-5351 (S)-1-fluoro-3-(2-(6-([C-11]methylamino)pyridin-3-yl)quinolin-6-yloxy)propan-2-ol. Tritium labeling and purification of [H-3]THK-5351 were undertaken using similar approach, resulting in [H-3]THK-5351 with RCP >99.8% and specific radioactivity of 13 GB q/mu mol. Results: [C-11]THK-5351 was produced in good yield (1900 +/- 355 MBq), specific radioactivity (SRA) (361 +/- 119 GBq/mu rnol at EOS + 20 min) and radiochemical purity (RCP) (>99.8%), with enantiomeric purity of 98.7%. [H-3]TM-5351 was evaluated for ARG of tau binding in post-mortem human brain tissue using cortical sections from one AD patient and one control subject. [H-3]THK-5351 binding density was higher in the AD patient compared to the control subject, the binding was displaced by unlabeled THK-5351 confirming specific [H-3] THK-5351 binding. (C) 2016 Elsevier Inc. All rights reserved.
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