| 1. |
- Jonsson, Pär, et al.
(författare)
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Constrained randomization and multivariate effect projections improve information extraction and biomarker pattern discovery in metabolomics studies involving dependent samples
- 2015
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Ingår i: Metabolomics. - : Springer. - 1573-3882 .- 1573-3890. ; 11:6, s. 1667-1678
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Tidskriftsartikel (refereegranskat)abstract
- Analytical drift is a major source of bias in mass spectrometry based metabolomics confounding interpretation and biomarker detection. So far, standard protocols for sample and data analysis have not been able to fully resolve this. We present a combined approach for minimizing the influence of analytical drift on multivariate comparisons of matched or dependent samples in mass spectrometry based metabolomics studies. The approach is building on a randomization procedure for sample run order, constrained to independent randomizations between and within dependent sample pairs (e.g. pre/post intervention). This is followed by a novel multivariate statistical analysis strategy allowing paired or dependent analyses of individual effects named OPLS-effect projections (OPLS-EP). We show, using simulated data that OPLS-EP gives improved interpretation over existing methods and that constrained randomization of sample run order in combination with an appropriate dependent statistical test increase the accuracy and sensitivity and decrease the false omission rate in biomarker detection. We verify these findings and prove the strength of the suggested approach in a clinical data set consisting of LC/MS data of blood plasma samples from patients before and after radical prostatectomy. Here OPLS-EP compared to traditional (independent) OPLS-discriminant analysis (OPLS-DA) on constrained randomized data gives a less complex model (3 versus 5 components) as well a higher predictive ability (Q2 = 0.80 versus Q2 = 0.55). We explain this by showing that paired statistical analysis detects 37 unique significant metabolites that were masked for the independent test due to bias, including analytical drift and inter-individual variation.
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| 2. |
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| 3. |
- Dahlén, Elin, et al.
(författare)
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Sibship and dispensing patterns of asthma medication in young children : a population based study
- 2019
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Ingår i: Pharmacoepidemiology & Drug Safety. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1053-8569 .- 1099-1557.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Our aim was to study the association between sibship and dispensing patterns of asthma medication in young children, focusing on incidence and persistence, and taking sibship status, asthma diagnoses, and siblings’ medication into account. Methods: A register-based cohort study including all children (n=50,546) born in Stockholm, Sweden 2006–2007, followed up during 2006–2014. Exposure was sibling status; outcome was incidence of dispensed asthma medication and persistence over time. A Cox-model was used to study the association between sibship and asthma medication. Persistence was defined using two different time windows (4- and 18-months) in a refill sequence model including siblings’ and unrelated control children’s medication. Results: After one year of age, the adjusted hazard ratio of dispensed asthma medication was 0.85 (95%CI 0.80–0.90) among children with siblings compared to singletons. The estimated proportion of children with persistent controller medication was 7.2% (4-month model) and 64.5% (18-month model). When including the siblings’ controller medication, the estimated proportion was 8.8% (4-months) and 7.8% for control children (relative risk, RR 0.89, 95%CI 0.81-0.98). The persistence was lower for those with siblings compared to singletons (adj. RR 0.72, 95%CI 0.62-0.85 for 4-months) with similar estimates for older, younger, and full siblings and regardless of asthma diagnoses. Conclusions: Siblings have different dispensing patterns of asthma medications compared to singletons regardless of asthma diagnoses. After including the siblings’ asthma medication and compared with control children, the proportion of children with persistent medication increased which may indicate that siblings share asthma medications.
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| 4. |
- Dürango, Sofie, et al.
(författare)
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Compliance with guidelines for postoperative pain management in infants and children
- 2017
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Ingår i: International Journal of Healthcare Management. - : Informa UK Limited. - 2047-9700 .- 2047-9719. ; 10:4, s. 259-264
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Tidskriftsartikel (refereegranskat)abstract
- Background: Postoperative pain is still often being inadequately assessed and/or recorded in infants and young children despite evidence-based guidelines. Objectives: This prospective, observational study in a paediatric postoperative ward at a Swedish university hospital was designed to evaluate interventional effects on pain management by briefly reminding nursing staff of corresponding local guidelines. Methods: Individual structured postoperative information on the first day and night after mainly otorhinolaryngeal or plastic surgery was obtained in 100 pediatric patients from on-site bedside observation protocols, patient records, and telephone interviews over two 5-week periods before and after a study intervention with brief systematic information on local guideline contents. Results: The intervention was followed by significantly more assessments (P = 0.0012), hourly assessments (P < 0.0001), and use of validated tools for assessment (P < 0.0001) of pain intensity in out-hospital patients, but by no change in guardian satisfaction. There were non-significant corresponding changes in in-hospital patients. Conclusions: Bedside compliance with guidelines for postoperative pain management can be considerably improved in out-hospital (and possibly also in-hospital) paediatric patients by a structured brief reminder of existing guideline contents. Larger prospective studies are required to determine the importance of bedside compliance with clinical guidelines for postoperative comfort and safety in infants and children.
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| 5. |
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| 6. |
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| 7. |
- Hansson, Martin, et al.
(författare)
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Tunga ting med text : Sivert Grubbe och eftermälet
- 2019
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Ingår i: Tidens landskap : En vänbok till Anders Andrén - En vänbok till Anders Andrén. - 0349-4128. - 9789188909121 ; :77, s. 48-50
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Bokkapitel (refereegranskat)abstract
- Den här artikeln diskuterar den danske adelsmannen Sivert Grubbe och de tavlor med långa inskrifter på latin som han satte upp på sina herrgårdar Torup och Hovdala på 1630-talet. Tavlorna sattes upp mot slutet av hans liv och kan ses som ett försök att skapa ett minnesmärke över sig själv, att styra det egna eftermälet.
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| 8. |
- Johannesson, Kerstin, 1955, et al.
(författare)
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Oceanographic barriers to gene flow promote genetic subdivision of the tunicate Ciona intestinalis in a North Sea archipelago
- 2018
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Ingår i: Marine Biology. - : Springer Science and Business Media LLC. - 0025-3162 .- 1432-1793. ; 165:8
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Tidskriftsartikel (refereegranskat)abstract
- Pelagic larval development has the potential to connect populations over large geographic distances and prevent genetic structuring. The solitary tunicate Ciona intestinalis has pelagic eggs and a swimming larval stage lasting for maximum a few days, with the potential for a homogenizing gene flow over relatively large areas. In the eastern North Sea, it is found in a geomorphologically complex archipelago with a mix of fjords and open costal habitats. Here, the coastal waters are also stratified with a marked pycnocline driven by salinity and temperature differences between shallow and deep waters. We investigated the genetic structure of C. intestinalis in this area and compared it with oceanographic barriers to dispersal that would potentially reduce connectivity among local populations. Genetic data from 240 individuals, sampled in 2 shallow, and 4 deep-water sites, showed varying degrees of differentiation among samples (F (ST) = 0.0-0.11). We found no evidence for genetic isolation by distance, but two distant deep-water sites from the open coast were genetically very similar indicating a potential for long-distance gene flow. However, samples from different depths from the same areas were clearly differentiated, and fjord samples were different from open-coast sites. A biophysical model estimating multi-generation, stepping-stone larval connectivity, and empirical data on fjord water mass retention time showed the presence of oceanographic barriers that explained the genetic structure observed. We conclude that the local pattern of oceanographic connectivity will impact on the genetic structure of C. intestinalis in this region.
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| 9. |
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| 10. |
- Jonsson, Ove, et al.
(författare)
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TIMFIE Sampler-A New Time-Integrating, Active, Low-Tech Sampling Device for Quantitative Monitoring of Pesticides in Whole Water
- 2019
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 53, s. 279-286
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Tidskriftsartikel (refereegranskat)abstract
- The need for inexpensive, time-averaged, quantitative determination of pesticides and other organic pollutants in whole water is not matched by the field sampling procedures available. Our new Time-Integrating, MicroFlow, In-line Extraction (TIMFIE) sampler comprises a low-tech syringe pump driven by a rubber band and connected to a flow restrictor enabling low microliter per minute water flow through a solid phase extraction (SPE) cartridge. This allows target compounds to be continuously extracted in the field over 1 week. The extracted water ends up in the syringe, where sample volume is accurately determined. TIMFIE followed by online SPE-LC-MS/MS determination was validated for 72 selected pesticides, and, except for three compounds, detection limit was 0.1-1 ng/L. In a field study, concentrations in TIMFIE samples and in grab samples were compared. Following TIMFIE sampling, on average 19 pesticides per sample were quantified, compared with nine pesticides per sample with grab sampling, as a result of the extra in-field concentration step. Duplicate TIMFIE sampling showed Pearson's correlation coefficient r = 0.998. Comparing concentrations from TIMFIE sampling to grab sampling resulted in ratios between 0.05 and 16.5 (mean 1.7; r = 0.532), demonstrating a discrepancy between the two sampling strategies and possible underestimation of chronic exposure by grab sampling.
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| 11. |
- Jonsson, Ulf, et al.
(författare)
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Adverse effects of psychological therapy : An exploratory study of practitioners' experiences from child and adolescent psychiatry
- 2016
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Ingår i: Clinical Child Psychology and Psychiatry. - : SAGE Publications. - 1359-1045 .- 1461-7021. ; 21:3, s. 432-446
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Tidskriftsartikel (refereegranskat)abstract
- The scientific knowledge about adverse effects of psychological therapies and how such effects should be detected is limited. It is possible that children and adolescents are particularly vulnerable and need specific support in order to express adverse effects. In this exploratory study, we used a qualitative approach to explore practitioners' experiences of this phenomenon. Fourteen practitioners providing psychological therapy within the Child and Adolescent Psychiatric Service were interviewed. Qualitative content analysis was applied to the data. Four overarching categories brought up by the practitioners were identified: vagueness of the concept (reflecting that the concept was novel and hard to define), psychotherapist-client interaction (encompassing aspects of the interaction possibly related to adverse effects), consequences for the young person (including a range of emotional, behavioural and social consequences) and family effects (e.g. professional complications and decreased autonomy for the parent). Professional discussions on these issues could improve psychological therapy for children and adolescents. Based on our findings and previous research, we propose three basic aspects to consider when adverse effects are detected and managed in this context: typology (form, severity and duration), aetiology (hypothesis about the causes) and perspective (adverse effects seen from the points of view of different interested parties).
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| 12. |
- Malmqvist, Elin, et al.
(författare)
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Two-dimensional OH-thermometry in reacting flows using photofragmentation laser-induced florescence
- 2016
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Ingår i: Combustion and Flame. - : Elsevier BV. - 0010-2180. ; 169, s. 297-306
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Tidskriftsartikel (refereegranskat)abstract
- In the present work, the possibility of using photofragmentation laser-induced fluorescence (PFLIF) for thermometry in different reacting flows is investigated. Hydroxyl (OH) fragments are created by UV-laser (266nm) fragmentation of hydrogen peroxides (H2O2 and HO2), whereupon the fluorescence, induced while scanning the wavelength of a second laser across the A2σ+(v = 1)-X2Π(v = 0) absorption band (around 282nm) of the generated OH fragments, is collected and detected. The temperature is determined by fitting simulated OH-excitation spectra of different temperatures to the experimentally recorded spectrum. In combustion, hydrogen peroxides are intermediate species formed during the low-temperature oxidation of the fuel, and hence they are present in a region covering a wide temperature span, ranging from unburnt to burnt gas temperatures. Thus, LIF of OH photofragments stemming from hydrogen peroxides allows for thermometry covering a wider temperature range than LIF of naturally present OH radicals. There is another important advantage of the concept in that the temperature sensitivity of OH excitation spectra is greater at lower temperatures. The method is demonstrated for two-dimensional (2-D) thermometry in three different measurement situations, namely a free flow of vaporized H2O2 at room temperature, a preheated mixture of CH4/N2/O2/O3 at intermediate temperatures (300-600K), where the OH fragments stem from photodissociation of O3 followed by chemical reactions, and in an optical homogeneous charge compression ignition (HCCI) engine prior to ignition, i.e. at elevated pressures and temperatures. It is found that the technique performs well in all three cases, with measured temperatures in good agreement with thermocouple readings, for the two first cases, and with temperatures calculated based on the ideal gas law using measured pressure traces as input for the engine measurements. The quantitative 2-D temperature images acquired in the engine experiments reveal inhomogeneous temperature distributions, clearly illustrating the capacity of the technique to yield crucial experimental input to engine modelers and designers. The accuracy of the technique in the temperature range 300-600K is lower than 23K. For the room temperature case the precision is 4.3%, corresponding to 12K.
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| 13. |
- Nordlund, Jessica, et al.
(författare)
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DNA methylation-based subtype prediction for pediatric acute lymphoblastic leukemia
- 2015
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Ingår i: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7083 .- 1868-7075. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: We present a method that utilizes DNA methylation profiling for prediction of the cytogenetic subtypes of acute lymphoblastic leukemia (ALL) cells from pediatric ALL patients. The primary aim of our study was to improve risk stratification of ALL patients into treatment groups using DNA methylation as a complement to current diagnostic methods. A secondary aim was to gain insight into the functional role of DNA methylation in ALL. Results: We used the methylation status of similar to 450,000 CpG sites in 546 well-characterized patients with T-ALL or seven recurrent B-cell precursor ALL subtypes to design and validate sensitive and accurate DNA methylation classifiers. After repeated cross-validation, a final classifier was derived that consisted of only 246 CpG sites. The mean sensitivity and specificity of the classifier across the known subtypes was 0.90 and 0.99, respectively. We then used DNA methylation classification to screen for subtype membership of 210 patients with undefined karyotype (normal or no result) or non-recurrent cytogenetic aberrations('other' subtype). Nearly half (n = 106) of the patients lacking cytogenetic subgrouping displayed highly similar methylation profiles as the patients in the known recurrent groups. We verified the subtype of 20% of the newly classified patients by examination of diagnostic karyotypes, array-based copy number analysis, and detection of fusion genes by quantitative polymerase chain reaction (PCR) and RNA-sequencing (RNA-seq). Using RNA-seq data from ALL patients where cytogenetic subtype and DNA methylation classification did not agree, we discovered several novel fusion genes involving ETV6, RUNX1, and PAX5. Conclusions: Our findings indicate that DNA methylation profiling contributes to the clarification of the heterogeneity in cytogenetically undefined ALL patient groups and could be implemented as a complementary method for diagnosis of ALL. The results of our study provide clues to the origin and development of leukemic transformation. The methylation status of the CpG sites constituting the classifiers also highlight relevant biological characteristics in otherwise unclassified ALL patients.
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| 14. |
- Näsström, Elin, et al.
(författare)
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Diagnostic metabolite biomarkers of chronic typhoid carriage
- 2018
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Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Salmonella Typhi and Salmonella Paratyphi A are the agents of enteric (typhoid) fever; both can establish chronic carriage in the gallbladder. Chronic Salmonella carriers are typically asymptomatic, intermittently shedding bacteria in the feces, and contributing to disease transmission. Detecting chronic carriers is of public health relevance in areas where enteric fever is endemic, but there are no routinely used methods for prospectively identifying those carrying Salmonella in their gallbladder.Methodology/Principal findings: Here we aimed to identify biomarkers of Salmonella carriage using metabolite profiling. We performed metabolite profiling on plasma from Nepali patients undergoing cholecystectomy with confirmed S. Typhi or S. Paratyphi A gallbladder carriage (and non-carriage controls) using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) and supervised pattern recognition modeling. We were able to significantly discriminate Salmonella carriage samples from non-carriage control samples. We were also able to detect differential signatures between S. Typhi and S. Paratyphi A carriers. We additionally compared carriage metabolite profiles with profiles generated during acute infection; these data revealed substantial heterogeneity between metabolites associated with acute enteric fever and chronic carriage. Lastly, we found that Salmonella carriers could be significantly distinguished from non-carriage controls using only five metabolites, indicating the potential of these metabolites as diagnostic markers for detecting chronic Salmonella carriers.Conclusions/Significance: Our novel approach has highlighted the potential of using metabolomics to search for diagnostic markers of chronic Salmonella carriage. We suggest further epidemiological investigations of these potential biomarkers in alternative endemic enteric fever settings.
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| 15. |
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| 16. |
- Toijer, Elin, et al.
(författare)
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H 2 O 2 and γ-radiation induced corrosion of 304L stainless steel in aqueous systems
- 2019
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Ingår i: Radiation Physics and Chemistry. - : Elsevier Ltd. - 0969-806X .- 1879-0895. ; 159, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- In light-water reactors the water used as neutron moderator and coolant is subjected to a constant radiation field which leads to the formation of a number of oxidizing and reducing species. In this work, the reactivity of the radiolysis product H 2 O 2 towards the 304L alloy, commonly used for structural materials in nuclear power plants, was investigated as well as oxidative dissolution of steel components as a consequence of γ-radiation and chemically added H 2 O 2 . The concentration of hydrogen peroxide as a function of time was monitored in the presence of different amounts of steel powder, and the second order reaction rate constant was determined to k 2 = (1.8 ± 0.2) × 10 −10 m s −1 . In the case of catalytic decomposition of hydrogen peroxide, hydroxyl radicals are formed which can be scavenged by methanol. In this reaction formaldehyde is formed, which can be detected spectroscopically. A high yield of formaldehyde was observed, indicating that catalytic decomposition is the main reaction path of H 2 O 2 in the current system. A significant contribution of the homogeneous Fenton reaction to both the reaction rate constant and the formaldehyde formation must however be considered, as Fe(II) will be released from the oxide layer in solution. In the case of γ-irradiation, an increased nickel content in solution compared to background experiments is seen. When the steel is subjected to chemically added hydrogen peroxide on the other hand, the chromium content in solution is increased. This indicates that the different types of exposure will impact different parts of the oxide layer characterized by different composition.
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| 17. |
- Trägårdh, Elin, et al.
(författare)
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Evaluation of inter-departmental variability of ejection fraction and cardiac volumes in myocardial perfusion scintigraphy using simulated data
- 2015
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Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Myocardial perfusion scintigraphy (MPS) is a clinically useful noninvasive imaging modality for diagnosing patients with suspected coronary artery disease. By utilizing gated MPS, the end diastolic volume (EDV) and end systolic volume (ESV) can be measured and the ejection fraction (EF) calculated, which gives incremental prognostic value compared with assessment of perfusion only. The aim of this study was to evaluate the inter-departmental variability of EF, ESV, and EDV during gated MPS in Sweden.Methods: Seventeen departments were included in the study. The SIMIND Monte Carlo (MC) program together with the XCAT phantom was used to simulate three patient cases with different EDV, ESV, and EF. Individual simulations were performed for each department, corresponding to their specific method of performing MPS. Images were then sent to each department and were evaluated according to clinical routine. EDV, ESV, and EF were reported back.Results: There was a large underestimation of EDV and ESV for all three cases. Mean underestimation for EDV varied between 26% and 52% and for ESV between 15% and 60%. EF was more accurately measured, but mean bias still varied between an underestimation of 24% to an overestimation of 14%. In general, the intra-departmental variability for EDV, ESV, and EF was small, whereas inter-departmental variability was larger.Conclusions: Left ventricular volumes were generally underestimated, whereas EF was more accurately estimated. There was, however, large inter-departmental variability.
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| 18. |
- Wallstén, Elin, et al.
(författare)
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PET/MRI attenuation correction in the pelvic region with a statistical decomposition method
- 2019
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. ; 46:SUPPL 1, s. S289-S290
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Aim/Introduction: Quantification in PET/MRI is of importance, and its accuracy is currently limited by the MR based attenuation correction estimate. A common method for attenuation correction of the pelvic region is based on a 2-echo Dixon MRI sequence for segmentation of fat and water and does not account for bone. In this work, we evaluate a new method for attenuation correction using an algorithm based on statistical decomposition of a T2 weighted MRI scan.Materials and Methods: Substitute CT images (sCTs) were calculated from T2 weighted MRI scans with a statistical decomposition algorithm, originally developed for MRI-based radiotherapy dose-planning [1]. These sCTs benefits from having bone density information included, in addition to fat and water information. Prostate cancer patients from the PARAPLY study [2] were retrospectivelyselected, scanned with PET/MRI 11C-Acatate and CT the same day. The stand-alone CT images were transformed to the same geometry as the PET and MR images, using a non-rigid registration. CT images, generated sCT images, and the Dixonbased attenuation maps (MRAC), all in the same geometry, were together with the PET raw data used to reconstruct attenuation-corrected PET images using the PETrecon toolbox [GE Healthcare]. The two MR-based attenuation corrections were compared to the CT-based attenuation correction with root mean squared error (RMSE). Lesion analysis will also be reported. PET/MRI images were acquired on a Signa PET/MRI (GE Healthcare), and the CT images on a Brilliance Big Bore (Phillips Healthcare). The study will include 12 patients and a subset of 6 patients has been analyzed so far and is presented here.Results: Soft tissue in-between pelvic bone structures were overestimated with 13% in MRAC-PET, and the error was reduced to 5% with sCT attenuation corrected PET (sCT-PET). For the whole patient volume, an average underestimation of 6% was found in the MRAC-PET, compared to 1% for sCTPET. RMSE within the body was reduced with a factor 2.5 with sCT-PET (RMSE=3.6%), compared to MRAC-PET (RMSE=8.8%).Conclusion: Applying sCT from statistical decomposition as a base for calculation of attenuation maps reduces quantification errors in PET-images of the pelvic region compared to the common Dixon based method.
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| 19. |
- Wienberg, Jes, et al.
(författare)
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Anders Andréns bibliografi
- 2019
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Ingår i: Tidens landskap : En vänbok till Anders Andrén - En vänbok till Anders Andrén. - 9789188909121 ; , s. 9-14
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 20. |
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| 21. |
- Östlund, Britt, 1956-, et al.
(författare)
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STS-inspired design to meet the challenges of modern aging : Welfare technology as a tool to promote user driven innovations or another way to keep older users hostage?
- 2015
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Ingår i: Technological forecasting & social change. - : Elsevier. - 0040-1625 .- 1873-5509. ; 93, s. 82-90
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Tidskriftsartikel (refereegranskat)abstract
- Older technology users and their integration into IT society have been on the research agenda since digitalization took off. Given the attempts to develop user-driven design, it is surprising that the appearance of technologies older people are provided with, or are the target group for, have not progressed. Now another political agenda, coined as "welfare technology", is being launched in Scandinavia. It is the reminiscent of previous arguments for why demographics, welfare and the need for new business arenas should be prioritized. This paper argues that STS-inspired design can contribute to a paradigm shift that breaks this trend and instead helps to develop proactive technology that meets the needs and demands of today's senior citizens. Two cases illustrate the way the imbalance between technology and older people's influence persists over time. Another three cases with a bearing on design sciences are singled out and discussed; the selection of older subjects; the understanding of the "social" in going from the laboratory to real-life settings; and the "making of meaning" in product development. The conclusions point to the opportunity to bridge the imbalance when introducing welfare technology by introducing STS-inspired reflections on engineering and design.
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