| 1. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 2. |
- Dahlberg, Tobias, et al.
(författare)
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Biophysical Fingerprinting of Single Bacterial Spores using Laser Raman Optical Tweezers
- 2020
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Ingår i: Chemical, biological, radiological, nuclear, and explosives (CBRNE) sensing XXI. - : SPIE-Intl Soc Optical Eng. - 9781510636101
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Konferensbidrag (refereegranskat)abstract
- Spore-forming bacteria that cause diseases pose a danger in our society. When in spore form, bacteria can survive high temperatures and resist a plethora of disinfection chemicals. Effective disinfection approaches are thus critical. Since a population of bacterial spores is heterogeneous in many aspects, single spore analyzing methods are suitable when heterogeneous information cannot be neglected. We present in this work a high-resolution Laser Raman optical tweezers that can trap single spores and characterize their Raman spectra. We first evaluate our system by measuring Raman spectra of spores, and purified DNA and DPA. Thereafter, we expose Bacillus thuringiensis spores to peracetic acid, chlorine dioxide, and sodium hypochlorite, which are common disinfection chemicals. The data reveals how these agents change the constitutes of a spore over time, thus improving on the mode of action of these disinfection chemicals.
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| 3. |
- Larsson, Johanna, et al.
(författare)
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Säkerhetskultur och självkörande fordon och maskiner
- 2024
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Självkörande fordon inom transportsektorn befinner sig ännu i utvecklingsstadiet. Att införa självkörande fordon och maskiner i befintliga verksamheter innebär ofta förändringar både i organisationen och den fysiska miljön och kan även innebära nya risker. I detta sammanhang kan säkerhetskulturen, både hos utvecklare och hos användare, spela viktig roll för att självkörande fordon och maskiner ska fungera säkert och effektivt i olika verksamheter. Projektets mål har varit att utveckla metoder för att förbättra säkerhetskultur där människor och automatiserad teknik samverkar som agenter i ett gemensamt system, samt att utveckla mätverktyg där hållbarhet, jämställdhet och säkerhet utvärderas för införande av självkörande fordon och maskiner. Projektet har utgått ifrån fallstudier från två olika domäner – självkörande bussar och självkörande industritruckar. Intervjuer har genomförts med utvecklare, kunder och slutanvändare. En enkät har tagits fram att mäta säkerhetskultur, jämställdhetskultur och hållbarhetskultur i organisationer som utvecklar självkörande fordon. Utöver detta har data från incidentrapporter analyserats. Lärdomarna från resultaten och projektdeltagarnas tidigare erfarenheter har resulterat i ett första utkast av en processmodell där säkerhetskultur integreras i utvecklingen av självkörande fordon och maskiner. Intervjuerna med utvecklare och kunder av självkörande fordon visade att säkerhetskultur inte var ett etablerat begrepp vare sig hos utvecklarna eller hos kunderna och att det därför inte var en faktor som man medvetet beaktade. Lärdomar från enkäten var att det finns skillnader mellan produktföretag och som markant påverkar formuleringar av frågeställningar. Det gick inte att fastställa om det föreligger kopplingar mellan hållbarhets-, jämställdhets- och säkerhetskultur. Fallstudien med bussarna visade bland annat att kund och leverantör pratar om olika typer av säkerhet samt att säkerheten ofta, men inte alltid, är prioriterad över effektiviteten. Utifrån analyserna av incidentdata från självkörande bussar samt förarlösa industritruckar har en lista med förslag på nyckeltal för att kunna analysera incidenter med självkörande fordon tagits fram inom projektet.
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| 4. |
- Lundquist, Patrik, et al.
(författare)
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Barriers to the Intestinal Absorption of Four Insulin-Loaded Arginine-Rich Nanoparticles in Human and Rat
- 2022
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 16:9, s. 14210-14229
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Tidskriftsartikel (refereegranskat)abstract
- Peptide drugs and biologics provide opportunities for treatments of many diseases. However, due to their poor stability and permeability in the gastrointestinal tract, the oral bioavailability of peptide drugs is negligible. Nanoparticle formulations have been proposed to circumvent these hurdles, but systemic exposure of orally administered peptide drugs has remained elusive. In this study, we investigated the absorption mechanisms of four insulin-loaded arginine-rich nanoparticles displaying differing composition and surface characteristics, developed within the pan-European consortium TRANS-INT. The transport mechanisms and major barriers to nanoparticle permeability were investigated in freshly isolated human jejunal tissue. Cytokine release profiles and standard toxicity markers indicated that the nanoparticles were nontoxic. Three out of four nanoparticles displayed pronounced binding to the mucus layer and did not reach the epithelium. One nanoparticle composed of a mucus inert shell and cell-penetrating octarginine (ENCP), showed significant uptake by the intestinal epithelium corresponding to 28 ± 9% of the administered nanoparticle dose, as determined by super-resolution microscopy. Only a small fraction of nanoparticles taken up by epithelia went on to be transcytosed via a dynamin-dependent process. In situ studies in intact rat jejunal loops confirmed the results from human tissue regarding mucus binding, epithelial uptake, and negligible insulin bioavailability. In conclusion, while none of the four arginine-rich nanoparticles supported systemic insulin delivery, ENCP displayed a consistently high uptake along the intestinal villi. It is proposed that ENCP should be further investigated for local delivery of therapeutics to the intestinal mucosa.
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| 5. |
- Malinovschi, Andrei, 1978-, et al.
(författare)
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Consequences of Using Post- or Prebronchodilator Reference Values in Interpreting Spirometry
- 2023
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 208:4, s. 461-471
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Post-bronchodilator (BD) spirometry is used for diagnosis of chronic obstructive pulmonary disease (COPD). However, pre-BD reference values are used for spirometry interpretation.OBJECTIVES: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using pre- or post-BD reference values generated within the Swedish CArdioPulmonary bioImage Study (SCAPIS) when interpreting post-BD spirometry in a general population.METHODS: SCAPIS reference values for post-BD and pre-BD spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or post-BD reference values, with respiratory burden in the SCAPIS general population (28,851 individuals).MEASUREMENTS AND MAIN RESULTS: Bronchodilation resulted in higher predicted median and lower limit of normal (LLN) for FEV1/FVC ratio. The prevalence of post-BD FEV1/FVC < pre-bronchodilator LLN was 4.8% and that of post-BD FEV1/FVC < post-bronchodilator LLN was 9.9% for the general population. An additional 5.1% was identified as having an abnormal post-BD FEV1/FVC ratio and this group had more respiratory symptoms, emphysema (13.5% vs. 4.1%, p<0.001) and self-reported physician-diagnosed COPD (2.8% vs. 0.5%, p<0.001) than subjects with post-BD FEV1/FVC ratio > LLN for both pre- and post-bronchodilation).CONCLUSIONS: Pre- and post-bronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of post-bronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using post-bronchodilator reference values when interpreting post-bronchodilator spirometry might enable identification of individuals with mild disease and be clinically relevant.
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| 6. |
- Malyshev, Dmitry, et al.
(författare)
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Laser induced degradation of bacterial spores during micro-Raman spectroscopy
- 2022
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Ingår i: Spectrochimica Acta Part A - Molecular and Biomolecular Spectroscopy. - : Elsevier. - 1386-1425 .- 1873-3557. ; 265
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Tidskriftsartikel (refereegranskat)abstract
- Micro-Raman spectroscopy combined with optical tweezers is a powerful method to analyze how the biochemical composition and molecular structures of individual biological objects change with time. In this work we investigate laser induced effects in the trapped object. Bacillus thuringiensis spores, which are robust organisms known for their resilience to light, heat, and chemicals are used for this study. We trap spores and monitor the Raman peak from CaDPA (calcium dipicolinic acid), which is a chemical protecting the spore core. We see a correlation between the amount of laser power used in the trap and the release of CaDPA from the spore. At a laser power of 5 mW, the CaDPA from spores in water suspension remain intact over the 90 min experiment, however, at higher laser powers an induced effect could be observed. SEM images of laser exposed spores (after loss of CaDPA Raman peak was confirmed) show a notable alteration of the spores' structure. Our Raman data indicates that the median dose exposure to lose the CaDPA peak was ∼60 J at 808 nm. For decontaminated/deactivated spores, i.e., treated in sodium hypochlorite or peracetic acid solutions, the sensitivity on laser power is even more pronounced and different behavior could be observed on spores treated by the two chemicals. Importantly, the observed effect is most likely photochemical since the increase of the spore temperature is in the order of 0.1 K as suggested by our numerical multiphysics model. Our results show that care must be taken when using micro-Raman spectroscopy on biological objects since photoinduced effects may substantially affect the results.
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| 7. |
- Malyshev, Dmitry, et al.
(författare)
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Mode of action of Disinfection chemicals on the bacterial spore structure and their Raman spectra
- 2021
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 93:6, s. 3146-3153
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Tidskriftsartikel (refereegranskat)abstract
- Contamination of toxic spore-forming bacteria is problematic since spores can survive a plethora of disinfection chemicals and it is hard to rapidly detect if the disinfection chemical has inactivated the spores. Thus, robust decontamination strategies and reliable detection methods to identify dead from viable spores are critical. In this work, we investigate the chemical changes of Bacillus thuringiensis spores treated with sporicidal agents such as chlorine dioxide, peracetic acid, and sodium hypochlorite using laser tweezers Raman spectroscopy. We also image treated spores using SEM and TEM to verify if we can correlate structural changes in the spores with changes to their Raman spectra. We found that over 30 min, chlorine dioxide did not change the Raman spectrum or the spore structure, peracetic acid showed a time-dependent decrease in the characteristic DNA/DPA peaks and ∼20% of the spores were degraded and collapsed, and spores treated with sodium hypochlorite showed an abrupt drop in DNA and DPA peaks within 20 min and some structural damage to the exosporium. Structural changes appeared in spores after 10 min, compared to the inactivation time of the spores, which is less than a minute. We conclude that vibrational spectroscopy provides powerful means to detect changes in spores but it might be problematic to identify if spores are live or dead after a decontamination procedure.
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| 8. |
- Malyshev, Dmitry, et al.
(författare)
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pH induced changes in Raman, UV-Vis absorbance, and fluorescence spectra of dipicolinic acid (DPA)
- 2022
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Ingår i: Spectrochimica Acta Part A - Molecular and Biomolecular Spectroscopy. - : Elsevier. - 1386-1425 .- 1873-3557. ; 271
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Tidskriftsartikel (refereegranskat)abstract
- Dipicolinic acid (DPA) is an essential component for the protection of DNA in bacterial endospores and is often used as a biomarker for spore detection. Depending upon the pH of the solution, DPA exists in different ionic forms. Therefore, it is important to understand how these ionic forms influence spectroscopic response. In this work, we characterize Raman and absorption spectra of DPA in a pH range of 2.0–10.5. We show that the ring breathing mode Raman peak of DPA shifts from 1003 cm−1 to 1017 cm−1 and then to 1000 cm−1 as pH increases from 2 to 5. The relative peak intensities related to the different ionic forms of DPA are used to experimentally derive the pKa values (2.3 and 4.8). We observe using UV–vis spectroscopy that the changes in the absorption spectrum of DPA as a function of pH correlate with the changes observed in Raman spectroscopy, and the same pKa values are verified. Lastly, using fluorescence spectroscopy and exciting a DPA solution at between 210–330 nm, we observe a shift in fluorescence emission from 375 nm to 425 nm between pH 2 and pH 6 when exciting at 320 nm. Our work shows that the different spectral responses from the three ionic forms of DPA may have to be taken into account in, e.g., spectral analysis and for detection applications.
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| 9. |
- Nordanstig, Joakim, et al.
(författare)
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Mortality with Paclitaxel-Coated Devices in Peripheral Artery Disease.
- 2020
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Ingår i: The New England journal of medicine. - : Massachusetts Medical Society. - 1533-4406 .- 0028-4793. ; 383, s. 2538-46
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Tidskriftsartikel (refereegranskat)abstract
- The results of a recent meta-analysis aroused concern about an increased risk of death associated with the use of paclitaxel-coated angioplasty balloons and stents in lower-limb endovascular interventions for symptomatic peripheral artery disease.We conducted an unplanned interim analysis of data from a multicenter, randomized, open-label, registry-based clinical trial. At the time of the analysis, 2289 patients had been randomly assigned to treatment with drug-coated devices (the drug-coated-device group, 1149 patients) or treatment with uncoated devices (the uncoated-device group, 1140 patients). Randomization was stratified according to disease severity on the basis of whether patients had chronic limb-threatening ischemia (1480 patients) or intermittent claudication (809 patients). The single end point for this interim analysis was all-cause mortality.No patients were lost to follow-up. Paclitaxel was used as the coating agent for all the drug-coated devices. During a mean follow-up of 2.49 years, 574 patients died, including 293 patients (25.5%) in the drug-coated-device group and 281 patients (24.6%) in the uncoated-device group (hazard ratio, 1.06; 95% confidence interval, 0.92 to 1.22). At 1 year, all-cause mortality was 10.2% (117 patients) in the drug-coated-device group and 9.9% (113 patients) in the uncoated-device group. During the entire follow-up period, there was no significant difference in the incidence of death between the treatment groups among patients with chronic limb-threatening ischemia (33.4% [249 patients] in the drug-coated-device group and 33.1% [243 patients] in the uncoated-device group) or among those with intermittent claudication (10.9% [44 patients] and 9.4% [38 patients], respectively).In this randomized trial in which patients with peripheral artery disease received treatment with paclitaxel-coated or uncoated endovascular devices, the results of an unplanned interim analysis of all-cause mortality did not show a difference between the groups in the incidence of death during 1 to 4 years of follow-up. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT02051088.).
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| 10. |
- Näsström, Thomas, et al.
(författare)
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Synthetic NAC 71-82 Peptides Designed to Produce Fibrils with Different Protofilament Interface Contacts
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 22:17
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Tidskriftsartikel (refereegranskat)abstract
- Alpha-synucleinopathies are featured by fibrillar inclusions in brain cells. Although α-synuclein fibrils display structural diversity, the origin of this diversity is not fully understood. We used molecular dynamics simulations to design synthetic peptides, based on the NAC 71-82 amino acid fragment of α-synuclein, that govern protofilament contacts and generation of twisted fibrillar polymorphs. Four peptides with structures based on either single or double fragments and capped or non-capped ends were selected for further analysis. We determined the fibrillar yield and the structures from these peptides found in the solution after fibrillisation using protein concentration determination assay and circular dichroism spectroscopy. In addition, we characterised secondary structures formed by individual fibrillar complexes using laser-tweezers Raman spectroscopy. Results suggest less mature fibrils, based on the lower relative β-sheet content for double- than single-fragment peptide fibrils. We confirmed this structural difference by TEM analysis which revealed, in addition to short protofibrils, more elongated, twisted and rod-like fibril structures in non-capped and capped double-fragment peptide systems, respectively. Finally, time-correlated single-photon counting demonstrated a difference in the Thioflavin T fluorescence lifetime profiles upon fibril binding. It could be proposed that this difference originated from morphological differences in the fibril samples. Altogether, these results highlight the potential of using peptide models for the generation of fibrils that share morphological features relevant for disease, e.g., twisted and rod-like polymorphs.
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| 11. |
- Orädd, Fredrik, et al.
(författare)
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Tracking the ATP-binding response in adenylate kinase in real time
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science. - 2375-2548. ; 7:47
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Tidskriftsartikel (refereegranskat)abstract
- The biological function of proteins is critically dependent on dynamics inherent to the native structure. Such structural dynamics obey a predefined order and temporal timing to execute the specific reaction. Determination of the cooperativity of key structural rearrangements requires monitoring protein reactions in real time. In this work, we used time-resolved x-ray solution scattering (TR-XSS) to visualize structural changes in the Escherichia coli adenylate kinase (AdK) enzyme upon laser-induced activation of a protected ATP substrate. A 4.3-ms transient intermediate showed partial closing of both the ATP- and AMP-binding domains, which indicates a cooperative closing mechanism. The ATP-binding domain also showed local unfolding and breaking of an Arg131-Asp146 salt bridge. Nuclear magnetic resonance spectroscopy data identified similar unfolding in an Arg131Ala AdK mutant, which refolded in a closed, substrate-binding conformation. The observed structural dynamics agree with a “cracking mechanism” proposed to underlie global structural transformation, such as allostery, in proteins.
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| 12. |
- Petersson, Jöran, et al.
(författare)
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Teaching dimensional analysis in secondary school mathematics
- 2021
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Ingår i: Abstract book nofa8. - : Western Norway University of Applied Sciences.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- AbstractIn its elementary form, the idea of dimensional analysis is to look at the unit of a magnitude, for example speed, and conclude that speed measured in m/s is a quotient having meters in the numerator and seconds in the denominator. However, despite dimensional analysis being a not un-common theme for research in mathematics education at tertiary level teaching, it seems in practice absent below that level. This is surprising since dimensional analysis is useful in mathematical problem solving involving proportionality. Even more so since, from halves and doubles in preschool to scalar multiplication in upper secondary school, proportionality permeates school mathematics and is well-researched (Lamon, 2007). Hence, the authors initiated a research project on how to teach dimensional analysis in school years 6-12. The novelty of this area made us choose didactical engineering (Artigue, 2015) as a theoretical framework suitable for developing the teaching of dimensional analysis. Accordingly, in a cycle of a priori and a posteriori analyses, the authors are developing an empirically based teaching model for dimensional analysis including the topic of constructing exercises for students. We present results from this on-going development project. ReferencesArtigue, M. (2015). Perspectives on Design Research: The Case of Didactical Engineering. In A. Bikner-Ahsbahs, C. Knipping, N. Presmeg. (Eds.). Approaches to Qualitative Research in Mathematics Education. Dordrecht: Springer.Lamon, S. J. (2007). Rational numbers and proportional reasoning: Towards a theoretical framework. In F.K. Lester (red) Second handbook of research on mathematics teaching and learning, vol 2 (pp. 629–668). Charlotte, NC: NCTM.
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| 13. |
- Öberg, Rasmus, et al.
(författare)
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Characterization of carfentanil and thiofentanil using surface-enhanced raman spectroscopy and density functional theory
- 2024
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Ingår i: Journal of Raman Spectroscopy. - : John Wiley & Sons. - 0377-0486 .- 1097-4555. ; 55:4, s. 481-492
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Tidskriftsartikel (refereegranskat)abstract
- Fentanyls are synthetic opioids up to 10,000 times more potent than morphine. Although initially developed for medical applications, fentanyl and its analogues have recently grown synonymous with the ongoing opioid epidemic. To combat the continued spread of these substances, there is a need for rapid and sensitive techniques for chemical detection. Surface-enhanced Raman spectroscopy (SERS) has the potential for trace detection of harmful chemical substances. However, vibrational spectra obtained by SERS often differ between SERS substrates, as well as compared with spectra from normal Raman (NR) spectroscopy. Herein, SERS and NR responses from two fentanyl analogues, carfentanil (CF) and thiofentanil (TF), were measured and analysed with support from density functional theory (DFT) modelling. Using commercially available silver nanopillar SERS substrates, the SERS signatures of samples diluted in acetonitrile between 0.01 and 1000 µg/mL were studied. Relative SERS peak intensities measured in the range of 220–1800 cm−1 vary with concentration, while SERS and NR spectra largely agree for CF at higher concentrations ((Formula presented.) 100 µg/mL). For TF, three distinct NR peaks at 262, 366 and 667 cm−1 are absent or strongly suppressed in the SERS spectrum, attributed to the lone-pair electrons of the thiophene's sulphur atom binding to the Ag surface. The concentration dependence of the Raman peak at (Formula presented.) 1000 cm−1, assigned to trigonal bending of the phenyl ring, approximately follows a Langmuir adsorption isotherm. This work elucidates similarities and differences between SERS and NR in fentanyl detection and discusses the chemical rationale behind these differences.
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| 14. |
- Öberg, Rasmus, et al.
(författare)
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UV-induced spectral and morphological changes in bacterial spores for inactivation assessment
- 2024
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 128:7, s. 1638-1646
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Tidskriftsartikel (refereegranskat)abstract
- The ability to detect and inactivate spore-forming bacteria is of significance within, for example, industrial, healthcare, and defense sectors. Not only are stringent protocols necessary for the inactivation of spores but robust procedures are also required to detect viable spores after an inactivation assay to evaluate the procedure’s success. UV radiation is a standard procedure to inactivate spores. However, there is limited understanding regarding its impact on spores’ spectral and morphological characteristics. A further insight into these UV-induced changes can significantly improve the design of spore decontamination procedures and verification assays. This work investigates the spectral and morphological changes to Bacillus thuringiensis spores after UV exposure. Using absorbance and fluorescence spectroscopy, we observe an exponential decay in the spectral intensity of amino acids and protein structures, as well as a logistic increase in dimerized DPA with increased UV exposure on bulk spore suspensions. Additionally, using micro-Raman spectroscopy, we observe DPA release and protein degradation with increased UV exposure. More specifically, the protein backbone’s 1600–1700 cm–1 amide I band decays slower than other amino acid-based structures. Last, using electron microscopy and light scattering measurements, we observe shriveling of the spore bodies with increased UV radiation, alongside the leaking of core content and disruption of proteinaceous coat and exosporium layers. Overall, this work utilized spectroscopy and electron microscopy techniques to gain new understanding of UV-induced spore inactivation relating to spore degradation and CaDPA release. The study also identified spectroscopic indicators that can be used to determine spore viability after inactivation. These findings have practical applications in the development of new spore decontamination and inactivation validation methods.
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| 15. |
- Abdulla, Maysaa, et al.
(författare)
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Cell-of-origin determined by both gene expression profiling and immunohistochemistry is the strongest predictor of survival in patients with diffuse large B-cell lymphoma
- 2020
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 95:1, s. 57-67
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Tidskriftsartikel (refereegranskat)abstract
- The tumor cells in diffuse large B-cell lymphomas (DLBCL) are considered to originate from germinal center derived B-cells (GCB) or activated B-cells (ABC). Gene expression profiling (GEP) is preferably used to determine the cell of origin (COO). However, GEP is not widely applied in clinical practice and consequently, several algorithms based on immunohistochemistry (IHC) have been developed. Our aim was to evaluate the concordance of COO assignment between the Lymph2Cx GEP assay and the IHC-based Hans algorithm, to decide which model is the best survival predictor. Both GEP and IHC were performed in 359 homogenously treated Swedish and Danish DLBCL patients, in a retrospective multicenter cohort. The overall concordance between GEP and IHC algorithm was 72%; GEP classified 85% of cases assigned as GCB by IHC, as GCB, while 58% classified as non-GCB by IHC, were categorized as ABC by GEP. There were significant survival differences (overall survival and progression-free survival) if cases were classified by GEP, whereas if cases were categorized by IHC only progression-free survival differed significantly. Importantly, patients assigned as non-GCB/ABC both by IHC and GEP had the worst prognosis, which was also significant in multivariate analyses. Double expression of MYC and BCL2 was more common in ABC cases and was associated with a dismal outcome. In conclusion, to determine COO both by IHC and GEP is the strongest outcome predictor to identify DLBCL patients with the worst outcome.
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| 16. |
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| 17. |
- Andree, Maria, et al.
(författare)
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Knowledge Products from Close-To-Practice Research
- 2024
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Ingår i: Round table presentation at the NERA-conference, 6-8 March, Malmö University.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- ‘Close-to-practice research’ has received increased attention across the Nordic countries. Following the British Education Research Association (BERA), the notion of ‘close-to-practice research’ is used to refer to educational research that is based on problems in practice, often involves researchers working in partnership with practitioners in schools and addresses issues of relevance to practitioners. This roundtable focuses on how close-to-practice research can contribute to the knowledge base of the teaching profession by bringing together perspectives from didactics, school improvement and educational policy. More specifically, the interest is directed toward what characterizes the knowledge produced through practice-based research that may have significance for teachers' professional knowledge base and practice. The roundtable conversation builds on a previous analysis of what kinds of knowledge products are generated in didactic close-to-practice research where teachers and researchers work together within the research environment Stockholm Teaching & Learning Studies. As a result of this analysis a typology of knowledge products was proposed including: (i) descriptions of knowing, (ii) teaching design, (iii) didactic examples and (iv) methodological tools. It has been proposed that additional knowledge products may be developed, such as artifacts to be used in teaching (e.g. lesson plans, visual representations). The roundtable will include the following points of discussion: 1) a brief presentation of the typology, 2) challenging and developing the typology of knowledge products proposed by previous research by investigating different cases of close-to-practice research from traditions of action research and practice-developing research within subject-didactics, and 3) discussing how the notion of knowledge products may contribute to advancing the conversation on cumulativity in the field of educational research in general, and in relation to syntheses of close-to-practice research in particular. The participants will be engaged in conversations on the desirability and feasibility of striving towards cumulativity.
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| 18. |
- Barucca, G., et al.
(författare)
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Feasibility studies for the measurement of time-like proton electromagnetic form factors from (p)over-barp -> mu(+)mu(-) at PANDA at FAIR
- 2021
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Ingår i: European Physical Journal A. - NEW YORK, USA : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:1
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, vertical bar G(E)vertical bar and vertical bar G(M)vertical bar, using the (p) over barp -> mu(+)mu(-) reaction at PANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at PANDA, using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is (p) over barp -> pi(+)pi(-), due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distributions of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented.
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| 19. |
- Barucca, G., et al.
(författare)
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PANDA Phase One
- 2021
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Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:6
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Tidskriftsartikel (refereegranskat)abstract
- The Facility for Antiproton and Ion Research (FAIR) in Darmstadt, Germany, provides unique possibilities for a new generation of hadron-, nuclear- and atomic physics experiments. The future antiProton ANnihilations at DArmstadt (PANDA or PANDA) experiment at FAIR will offer a broad physics programme, covering different aspects of the strong interaction. Understanding the latter in the non-perturbative regime remains one of the greatest challenges in contemporary physics. The antiproton-nucleon interaction studied with PANDA provides crucial tests in this area. Furthermore, the high-intensity, low-energy domain of PANDA allows for searches for physics beyond the Standard Model, e.g. through high precision symmetry tests. This paper takes into account a staged approach for the detector setup and for the delivered luminosity from the accelerator. The available detector setup at the time of the delivery of the first antiproton beams in the HESR storage ring is referred to as the Phase One setup. The physics programme that is achievable during Phase One is outlined in this paper.
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| 20. |
- Barucca, G., et al.
(författare)
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Study of excited Ξ baryons with the P¯ ANDA detector
- 2021
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Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
-
Tidskriftsartikel (refereegranskat)abstract
- The study of baryon excitation spectra provides insight into the inner structure of baryons. So far, most of the world-wide efforts have been directed towards N∗ and Δ spectroscopy. Nevertheless, the study of the double and triple strange baryon spectrum provides independent information to the N∗ and Δ spectra. The future antiproton experiment P¯ANDA will provide direct access to final states containing a Ξ¯ Ξ pair, for which production cross sections up to μb are expected in p¯p reactions. With a luminosity of L= 10 31 cm- 2 s- 1 in the first phase of the experiment, the expected cross sections correspond to a production rate of ∼106events/day. With a nearly 4 π detector acceptance, P¯ANDA will thus be a hyperon factory. In this study, reactions of the type p¯p → Ξ¯ +Ξ∗ - as well as p¯p → Ξ¯ ∗ +Ξ- with various decay modes are investigated. For the exclusive reconstruction of the signal events a full decay tree fit is used, resulting in reconstruction efficiencies between 3 and 5%. This allows high statistics data to be collected within a few weeks of data taking.
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| 21. |
- Barucca, G., et al.
(författare)
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The potential of Λ and Ξ- studies with PANDA at FAIR
- 2021
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Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
-
Tidskriftsartikel (refereegranskat)abstract
- The antiproton experiment PANDA at FAIR is designed to bring hadron physics to a new level in terms of scope, precision and accuracy. In this work, its unique capability for studies of hyperons is outlined. We discuss ground-state hyperons as diagnostic tools to study non-perturbative aspects of the strong interaction, and fundamental symmetries. New simulation studies have been carried out for two benchmark hyperon-antihyperon production channels: p¯ p→ Λ¯ Λ and p¯ p→ Ξ¯ +Ξ-. The results, presented in detail in this paper, show that hyperon-antihyperon pairs from these reactions can be exclusively reconstructed with high efficiency and very low background contamination. In addition, the polarisation and spin correlations have been studied, exploiting the weak, self-analysing decay of hyperons and antihyperons. Two independent approaches to the finite efficiency have been applied and evaluated: one standard multidimensional efficiency correction approach, and one efficiency independent approach. The applicability of the latter was thoroughly evaluated for all channels, beam momenta and observables. The standard method yields good results in all cases, and shows that spin observables can be studied with high precision and accuracy already in the first phase of data taking with PANDA.
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| 22. |
- Bergström, Göran, et al.
(författare)
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Self-report tool for identification of individuals with coronary atherosclerosis : the Swedish cardiopulmonary bioimage study
- 2024
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 13:14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis.METHODS AND RESULTS: We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P<0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly.CONCLUSIONS: We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.
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| 23. |
- Davi, F., et al.
(författare)
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Technical design report for the endcap disc DIRC
- 2022
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Ingår i: Journal of Physics G. - : Institute of Physics Publishing (IOPP). - 0954-3899 .- 1361-6471. ; 49:12
-
Tidskriftsartikel (refereegranskat)abstract
- PANDA (anti-proton annihiliation at Darmstadt) is planned to be one of the four main experiments at the future international accelerator complex FAIR (Facility for Antiproton and Ion Research) in Darmstadt, Germany. It is going to address fundamental questions of hadron physics and quantum chromodynamics using cooled antiproton beams with a high intensity and and momenta between 1.5 and 15 GeV/c. PANDA is designed to reach a maximum luminosity of 2 × 1032 cm−2 s. Most of the physics programs require an excellent particle identification (PID). The PID of hadronic states at the forward endcap of the target spectrometer will be done by a fast and compact Cherenkov detector that uses the detection of internally reflected Cherenkov light (DIRC) principle. It is designed to cover the polar angle range from 5° to 22° and to provide a separation power for the separation of charged pions and kaons up to 3 standard deviations (s.d.) for particle momenta up to 4 GeV/c in order to cover the important particle phase space. This document describes the technical design and the expected performance of the novel PANDA disc DIRC detector that has not been used in any other high energy physics experiment before. The performance has been studied with Monte-Carlo simulations and various beam tests at DESY and CERN. The final design meets all PANDA requirements and guarantees sufficient safety margins.
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| 24. |
- Englund, Johanna, 1988, et al.
(författare)
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Deactivation of a Vanadium-Based SCR Catalyst Used in a Biogas-Powered Euro VI Heavy-Duty Engine Installation
- 2020
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Ingår i: Catalysts. - : MDPI AG. - 2073-4344. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated how the exhaust gases from a heavy-duty Euro VI engine, powered with biogas impact a vanadium-based selective catalytic reduction (SCR) catalyst in terms of performance. A full Euro VI emission control system was used and the accumulation of catalyst poisons from the combustion was investigated for the up-stream particulate filter as well as the SCR catalyst. The NO(x)reduction performance in terms of standard, fast and NO2-rich SCR was evaluated before and after exposure to exhaust from a biogas-powered engine for 900 h. The SCR catalyst retains a significant part of its activity towards NO(x)reduction after exposure to biogas exhaust, likely due to capture of catalyst poisons on the up-stream components where the deactivation of the oxidation catalyst is especially profound. At lower temperatures some deactivation of the first part of the SCR catalyst was observed which could be explained by a considerably higher surface V4+/V(5+)ratio for this sample compared to the other samples. The higher value indicates that the reoxidation of V(4+)to V(5+)is partially hindered, blocking the redox cycle for parts of the active sites.
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| 25. |
- Fegraeus, Kim, et al.
(författare)
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An endothelial regulatory module links blood pressure regulation with elite athletic performance
- 2024
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 20:6
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Tidskriftsartikel (refereegranskat)abstract
- The control of transcription is crucial for homeostasis in mammals. A previous selective sweep analysis of horse racing performance revealed a 19.6 kb candidate regulatory region 50 kb downstream of the Endothelin3 (EDN3) gene. Here, the region was narrowed to a 5.5 kb span of 14 SNVs, with elite and sub-elite haplotypes analyzed for association to racing performance, blood pressure and plasma levels of EDN3 in Coldblooded trotters and Standardbreds. Comparative analysis of human HiCap data identified the span as an enhancer cluster active in endothelial cells, interacting with genes relevant to blood pressure regulation. Coldblooded trotters with the sub-elite haplotype had significantly higher blood pressure compared to horses with the elite performing haplotype during exercise. Alleles within the elite haplotype were part of the standing variation in pre-domestication horses, and have risen in frequency during the era of breed development and selection. These results advance our understanding of the molecular genetics of athletic performance and vascular traits in both horses and humans.
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| 26. |
- Gdaniec, Sandra, 1988-
(författare)
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231Pa, 230Th and 232Th as tracers of deep water circulation and particle transport : Insights from the Mediterranean Sea and the Arctic Ocean
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The naturally occurring U and Th-series radionuclides have shown to have a considerable importance for the understanding of biogeochemical processes on Earth and in the ocean. In this thesis, the isotopes 230-thorium (230Th), 232-thorium (232Th) and 231-protactinium (231Pa) are used as tracers of the transport and scavenging of marine particles and water circulation. Pa and Th are particle reactive elements, which makes the production, transport and distribution of Pa and Th key factors for our understanding of the origin, fate and distribution of marine particles in the oceans. This thesis explores the distribution of 231Pa, 230Th and 232Th in two different ocean continental margin environments. In particular, the relative influence of water circulation and particles on the 231Pa, 230Th and 232Th distributions in the Arctic Ocean and Mediterranean Sea was investigated. 231Pa, 230Th and 232Th were analyzed in particles and seawater collected in the Mediterranean Sea during the MedSeA-GA04-S cruise along the GEOTRACES section GA04S and in the Arctic Ocean during the PS94 GN04 ARK-XXIX/3 along the GEOTRACES section GN04.One of the important findings of this thesis was the low fractionation between 231Pa and 230Th in the Mediterranean Sea, contrasting what is observed in the open ocean. Additionally, the observed depth profiles of Pa-Th allowed the identification of deep water convection and ventilation in the Western and Eastern Basins, respectively. Moreover, the particle settling speed was reevaluated to ~500 – 1000 m/y.In the Arctic Ocean, scavenging onto particles derived from hydrothermal activity was producing relatively low F-factors (FTh/Pa ~ 10), while higher values were observed in deep waters (FTh/Pa ~ 20). Additionally, the hydrothermal particles in the Nansen interior produce lower FTh/Pa values compared to FTh/Pa observed at the Nansen continental margin. Application of a boundary scavenging model revealed the importance of 230Th scavenging at the continental margin along the Nansen Basin, hereafter the Nansen margin, and advocate for the advection of 231Pa into the Atlantic Ocean. As the ocean margin was included in this model, a particle settling speed of 600 m/y was obtained at the Nansen margin.Moreover, this thesis includes an inter-comparison of dissolved and particulate 231Pa, 230Th and 232Th measurements between four laboratories of the GEOTRACES community. This comparison was conducted to provide detailed descriptions of various chemical procedures used for Pa-Th analysis and to provide a measure of consistency between the laboratories. Results demonstrated that participating labs can determine concentrations of dissolved 230Th and 231Pa in deep water (below 500 m depth) that are internally consistent within 4 % of the mean values. Analysis of particulate 231Pa, 230Th and 232Th allowed the highlighting of an incomplete Pa dissolution problem with our initial leaching procedure, a problem solved by measuring aliquots of particulate samples at two labs. However, in the present work, consistent particulate 231Pa concentrations as low as ~ 0.002 fg/kg were obtained. Overall, it suggests an improvement of the results consistency compared to the previous GEOTRACES intercalibration exercise.
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| 27. |
- Guo, Zongxin, et al.
(författare)
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Diverse roles of the metal binding domains and transport mechanism of copper transporting P-type ATPases
- 2024
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15
-
Tidskriftsartikel (refereegranskat)abstract
- Copper transporting P-type (P1B-1-) ATPases are essential for cellular homeostasis. Nonetheless, the E1-E1P-E2P-E2 states mechanism of P1B-1-ATPases remains poorly understood. In particular, the role of the intrinsic metal binding domains (MBDs) is enigmatic. Here, four cryo-EM structures and molecular dynamics simulations of a P1B-1-ATPase are combined to reveal that in many eukaryotes the MBD immediately prior to the ATPase core, MBD−1, serves a structural role, remodeling the ion-uptake region. In contrast, the MBD prior to MBD−1, MBD−2, likely assists in copper delivery to the ATPase core. Invariant Tyr, Asn and Ser residues in the transmembrane domain assist in positioning sulfur-providing copper-binding amino acids, allowing for copper uptake, binding and release. As such, our findings unify previously conflicting data on the transport and regulation of P1B-1-ATPases. The results are critical for a fundamental understanding of cellular copper homeostasis and for comprehension of the molecular bases of P1B-1-disorders and ongoing clinical trials.
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| 28. |
- Hirst, Catherine, 1989-, et al.
(författare)
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Iron isotopes reveal seasonal variations in the mechanisms for iron-bearing particle and colloid formation in the Lena River catchment, NE Siberia
- 2023
-
Ingår i: Geochimica et Cosmochimica Acta. - 0016-7037 .- 1872-9533. ; 363, s. 77-93
-
Tidskriftsartikel (refereegranskat)abstract
- Large Arctic rivers are an important source of iron (Fe) to the Arctic Ocean, though seasonal variations in the terrestrial source and supply of Fe to the ocean are unknown. To constrain the seasonal variability, we present Fe concentrations and isotopic compositions (δ56Fe) for particulate (>0.22 µm) and colloidal (<0.22 µm–1 kDa) Fe from the Lena River, NE Russia. Samples were collected every month during winter baseflow (September 2012–March 2013) and every 2–3 days before, during and after river ice break-up (May 2015).Iron in particles have isotope ratios lower than crustal values during winter (e.g., δ56FePart = −0.37 ± 0.16‰), and crustal-like values during river ice break-up and spring flood (e.g., δ56FePart = 0.07 ± 0.08‰), indicating a change in the source of particulate Fe between winter and spring flood. Low isotope values are indicative of mineral dissolution, transport of reduced Fe in sub-oxic, ice-covered sub-permafrost groundwaters and near-quantitative precipitation of Fe as particles. Crustal-like isotopic compositions result from the increased supply of detrital particles from riverbank and soil erosion during river ice break-up and flooding. Iron colloids (<0.22 μm) have δ56Fe values that are comparable to or lower than crustal values during winter (e.g., δ56FeCol = −0.08 ± 0.05‰) but similar to or higher than crustal values during spring flood (e.g., δ56FeCol = +0.24 ± 0.11‰). Low δ56Fe ratios for colloidal Fe during winter are consistent with precipitation from isotopically light Fe(II)aq transported in sub-permafrost groundwaters. Higher colloidal δ56Fe ratios during the spring flood indicate that these colloids are supplied from surface soils, where Fe is fractionated via oxidation or organic carbon complexation, similar to during summer. Approximately half of the annual colloidal Fe flux occurs during spring flood while most of the remaining colloidal Fe is supplied during summer months. The total amount of colloidal Fe transported during winter was relatively low. The seasonal variation in colloidal Fe isotope values may be a useful tool to trace the source of colloidal Fe to the Arctic Ocean and monitor future changes in the sources and supply of Fe from the permafrost landscape to the Lena River basin.
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| 29. |
- Hirst, Catherine, et al.
(författare)
-
Iron isotopes reveal the sources of Fe-bearing particles and colloids in the Lena River basin
- 2020
-
Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier BV. - 0016-7037 .- 1872-9533. ; 269, s. 678-692
-
Tidskriftsartikel (refereegranskat)abstract
- Large Arctic rivers are important suppliers of iron to the Arctic Ocean. However, the sources of Fe-bearing particles in permafrost-dominated systems and the mechanisms driving this supply of Fe are poorly resolved. Here, Fe isotope ratios were used to determine the sources of Fe-bearing particles and colloids in the Lena River and tributaries. In samples collected after the spring floods, Fe-bearing particles (>0.22 mu m) carried similar to 70% of the Fe and have isotope ratios that are lower than, or similar to that of the continental crust. These particles are composed of a leachable Fe fraction of largely ferrihydrite, with isotope values of -1.40 parts per thousand to -0.12 parts per thousand, and a fraction of clays and Fe oxides with continental crust values. Co-existing Fe-bearing colloids (<0.22 mu m), composed mainly of ferrihydrite, have higher isotope values, of -0.22 parts per thousand to +1.83 parts per thousand. A model is proposed in which soil mineral weathering generates aqueous Fe with lower delta Fe-56 values. During transport, a small fraction of the dissolved Fe is precipitated as colloidal ferrihydrite with higher delta Fe-56 values. Most of the Fe is precipitated onto mineral grains in oxic riparian zones, with the delta Fe-56 values largely generated during weathering. Groundwater discharge and riparian erosion supply the colloids and coated particles to the rivers. The differences between delta Fe-56 values in leachates and detrital grains in Fe-bearing particles agree with values determined in mineral dissolution experiments and in Fe accumulation horizons in soils. The difference in delta Fe-56 values between leachates and colloids reflects isotope fractionation during incremental Fe(III)(aq) precipitation and Fe-OC complexation during transport towards the riparian zone. Overall, the Fe isotope values of riverine particles and colloids reflect processes that occur during mineral dissolution, transport, and secondary mineral formation in permafrost soils.
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| 30. |
- Katsogiannos, Petros, 1979-
(författare)
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Bariatric surgery as treatment of type 2 diabetes – clinical and mechanistic aspects
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bariatric surgery can rapidly improve glycemic control and cardiovascular risk factors in patients with T2D and obesity. These improvements appear to be partly independent of weight loss, however, the underlying mechanisms remain incompletely understood. A randomized controlled trial was designed where 19 patients with obesity and T2D were either operated with a Roux-en-Y gastric bypass (RYGB) operation or continued with standard-of-care treatment and followed up for 2 years, providing the data for Paper I-III.In paper I, we focused on changes in whole-body glucose metabolism in relation to changes in adipose tissue metabolism and morphology. We observed an early adipose tissue remodeling and a reduction in adipocyte size that however, did not correlate to the early improvements in metabolic control.In paper II, we analyzed the neuroendocrine changes after RYGB. We observed changes within 4 weeks with signs of enhanced parasympathetic outlow, reduced morning cortisol, and enhanced incretin and glucagon responses to glucose, suggesting that neurohormonal mechanisms can contribute to the rapid improvement of insulin resistance and glycemia following RYGB in T2D.In paper III the patients from the RYGB group were interviewed 2 years after surgery to examine the effects of surgery on health-related quality of life (HRQoL). We found that the improved HRQoL after RYGB was not explained specifically by the magnitude of weight loss, but rather by the participants achieving a state of union between body and consciousness.In paper IV, we compared changes in circulating cytokine and adipokine levels in obese patients with- and without T2D. We observed that the cytokine profile of these patients is altered when compared to lean healthy control subjects and persist to a large extent after RYGB despite the weight loss and improved metabolic status.In conclusion, we observed that in the early post-operative period, neurohormonal changes appear to be more important than adipose tissue changes in improving insulin sensitivity and leading to diabetes remission.In the qualitative part of our study, we observed that the improved HRQoL was not solely explained by weight loss
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| 31. |
- Larfors, Gunnar, et al.
(författare)
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Despite warnings, co-medication with proton pump inhibitors and dasatinib is common in chronic myeloid leukemia, but XS004, a novel oral dasatinib formulation, provides reduced pH-dependence, minimizing undesirable drug-drug interactions.
- 2023
-
Ingår i: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609.
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dasatinib and other tyrosine kinase inhibitors (TKI) have revolutionized the treatment of chronic myeloid leukemia (CML). However, as a lipophilic weak base, crystalline monohydrate, dasatinib (Sprycel®) is poorly soluble, rendering a pH-dependent absorption and a highly variable bioavailability. Thus, co-medication with proton pump inhibitors (PPI) profoundly impairs dasatinib uptake and is clearly recommended against. XS004 is a novel oral immediate release and amorphous solid dispersion (ASD) formulation of dasatinib and is bioequivalent to the original crystalline dasatinib at 30% lower dosages. XS004 is designed to mitigate gastric pH dependency, thus optimizing absorption and bioavailability.METHODS: We investigated the prevalence of dasatinib and PPI co-medication among chronic-phase CML patients in a real-world setting and assessed the plasma pharmacokinetics (PK) of XS004 with and without PPI co-medication (omeprazole) in healthy volunteers.RESULTS: Using the Swedish CML and Prescribed Drug Registers, we identified 676 TKI-treated CML patients; 320 (47%) had been prescribed PPI at some point after CML diagnosis. Among dasatinib-treated patients, the 2-year cumulative PPI co-medication was 24%. Interestingly, the 5-year overall survival was significantly lower for TKI-treated CML patients with versus without PPI co-medication (79% vs. 94%; hazard ratio 3.5; 95% confidence interval, 2.1-5.3; p < .0001). When assessing PK of XS004, neither Cmax nor area under the plasma concentration curve levels in plasma were significantly altered by the PPI co-medication.CONCLUSION: In conclusion, despite warnings, PPI co-medication is common among dasatinib-treated CML patients in a real-world setting. The new XS004 ASD formulation of dasatinib provided, in contrast to original crystalline dasatinib, superior pH independence with stable bioavailability, thereby minimizing drug-drug interactions. This may improve the long-term efficacy and tolerability of dasatinib in CML.
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| 32. |
- Larsson, Simon B., et al.
(författare)
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Self-reported symptom severity, general health, and impairment in post-acute phases of COVID-19: retrospective cohort study of Swedish public employees
- 2022
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- This study aimed to examine current symptom severity and general health in a sample of primarily non-hospitalized persons with polymerase chain reaction (PCR) confirmed COVID-19 in comparison to PCR negative controls. During the first quarter of 2021, we conducted an online survey among public employees in West Sweden, with a valid COVID-19 test result. The survey assessed past-month severity of 28 symptoms and signs, self-rated health, the WHO Disability Assessment Schedule (WHODAS) 2.0 and illness severity at the time of test. We linked participants' responses to their SARS-CoV-2 PCR tests results. We compared COVID-19 positive and negative participants using univariable and multivariable regression analyses. Out of 56,221 invited, 14,222 (25.3%) responded, with a response rate of 50% among SARS-CoV-2 positive individuals. Analysis included 10,194 participants (86.4% women, mean age 45 years) who tested positive 4-12 weeks (N = 1425; subacute) and > 12 weeks (N = 1584; postcovid) prior to the survey, and 7185 PCR negative participants who did not believe that they had had COVID-19. Symptoms were highly prevalent in all groups, with worst symptoms in subacute phase participants, followed by postcovid phase and PCR negative participants. The most specific symptom for COVID-19 was loss of smell or taste. Both WHODAS 2.0 score and self-rated health were worst in subacute participants, and modestly worse in postcovid participants than in negative controls. Female gender, older age and acute illness severity had larger effects on self-rated health and WHODAS 2.0 score in PCR positive participants than in PCR negative. Studies with longer follow-up are needed to determine the long-term improvement after COVID-19.
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| 33. |
- Moreno, Maiara, 1993-, et al.
(författare)
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Strain and phase evolution in TiAlN coatings during high-speed metal cutting : An in operando high-energy x-ray diffraction study
- 2024
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Ingår i: Acta Materialia. - : Elsevier. - 1359-6454 .- 1873-2453. ; 263
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Tidskriftsartikel (refereegranskat)abstract
- We report on phase and strain changes in Ti1-xAlxN (0 ≤ x ≤ 0.61) coatings on cutting tools during turning recorded in operando by high-energy x-ray diffractometry. Orthogonal cutting of AISI 4140 steel was performed with cutting speeds of 360–370 m/min. Four positions along the tool rake face were investigated as a function of time in cut. Formation of γ-Fe in the chip reveals that the temperature exceeds 727 °C between the tool edge and the middle of the contact area when the feed rate is 0.06 mm/rev. Spinodal decomposition and formation of wurtzite AlN occurs at the positions of the tool with the highest temperature for the x ≥ 0.48 coatings. The strain evolution in the chip reveals that the mechanical stress is largest closest to the tool edge and that it decreases with time in cut for all analyzed positions on the rake face. The strain evolution in the coating varies between coatings and position on the rake face of the tool and is affected by thermal stress as well as the applied mechanical stress. Amongst others, the strain evolution is influenced by defect annihilation and, for the coatings with highest Al-content (x ≥ 0.48), phase changes.
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| 34. |
- Niklasson, Erik, et al.
(författare)
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Assessment of anterior thigh muscle size and fat infiltration using single-slice CT imaging versus automated MRI analysis in adults
- 2022
-
Ingår i: British Journal of Radiology. - London, United Kingdom : British Institute of Radiology. - 0007-1285 .- 1748-880X. ; 95:1133
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: We examined the longitudinal and cross- sectional relationship between automated MRI-analysis and single-slice axial CT imaging for determining muscle size and muscle fat infiltration (MFI) of the anterior thigh.Methods: Twenty-two patients completing sex-hormone treatment expected to result in muscle hypertrophy (n = 12) and atrophy (n = 10) underwent MRI scans using 2-point Dixon fat/water-separated sequences and CT scans using a system operating at 120 kV and a fixed flux of 100 mA. At baseline and 12 months after, auto- mated volumetric MRI analysis of the anterior thigh was performed bilaterally, and fat-free muscle volume and MFI were computed. In addition, cross-sectional area (CSA) and radiological attenuation (RA) (as a marker of fat infiltration) were calculated from single slice axial CT-images using threshold-assisted planimetry. Linear regression models were used to convert units.Results: There was a strong correlation between MRI- derived fat-free muscle volume and CT-derived CSA (R = 0.91), and between MRI-derived MFI and CT-derived RA (R = −0.81). The 95% limits of agreement were ±0.32 L for muscle volume and ±1.3% units for %MFI. The longi- tudinal change in muscle size and MFI was comparable across imaging modalities.Conclusions: Both automated MRI and single-slice CT-imaging can be used to reliably quantify anterior thigh muscle size and MFI.Advances in knowledge: This is the first study examining the intermodal agreement between automated MRI anal- ysis and CT-image assessment of muscle size and MFI in the anterior thigh muscles. Our results support that both CT- and MRI-derived measures of muscle size and MFI can be used in clinical settings.
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| 35. |
- Sonderby, Ida E., et al.
(författare)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
-
Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
-
Tidskriftsartikel (refereegranskat)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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| 36. |
- Sønderby, Ida E., et al.
(författare)
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1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
- 2021
-
Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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| 37. |
- Thomen, Aurélien, et al.
(författare)
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Subcellular Mass Spectrometry Imaging and Absolute Quantitative Analysis across Organelles
- 2020
-
Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 14:4, s. 4316-4325
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Tidskriftsartikel (refereegranskat)abstract
- Mass spectrometry imaging is a field that promises to become a mainstream bioanalysis technology by allowing the combination of single-cell imaging and subcellular quantitative analysis. The frontier of single-cell imaging has advanced to the point where it is now possible to compare the chemical contents of individual organelles in terms of raw or normalized ion signal. However, to realize the full potential of this technology, it is necessary to move beyond this concept of relative quantification. Here we present a nanoSIMS imaging method that directly measures the absolute concentration of an organelle-associated, isotopically labeled, pro-drug directly from a mass spectrometry image. This is validated with a recently developed nanoelectrochemistry method for single organelles. We establish a limit of detection based on the number of isotopic labels used and the volume of the organelle of interest, also offering this calculation as a web application. This approach allows subcellular quantification of drugs and metabolites, an overarching and previously unmet goal in cell science and pharmaceutical development.
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| 38. |
- van der Meer, Dennis, et al.
(författare)
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Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
- 2020
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
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| 39. |
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| 40. |
- Wegler, Christine, et al.
(författare)
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Global variability analysis of mRNA and protein concentrations across and within human tissues
- 2020
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Ingår i: NAR Genomics and Bioinformatics. - : Oxford University Press (OUP). - 2631-9268. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Genes and proteins show variable expression patterns throughout the human body. However, it is not clear whether relative differences in mRNA concentrations are retained on the protein level. Furthermore, inter-individual protein concentration variability within single tissue types has not been comprehensively explored. Here, we used the Gini index for in-depth concentration variability analysis of publicly available transcriptomics and proteomics data, and of an in-house proteomics dataset of human liver and jejunum from 38 donors. We found that the transfer of concentration variability from mRNA to protein is limited, that established ‘reference genes’ for data normalization vary markedly at the protein level, that protein concentrations cover a wide variability spectrum within single tissue types, and that concentration variability analysis can be a convenient starting point for identifying disease-associated proteins and novel biomarkers. Our results emphasize the importance of considering individual concentration levels, as opposed to population averages, for personalized systems biology analysis.
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| 41. |
- Westphal Ladfors, Susanne, et al.
(författare)
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Long-lasting chronic high load carriage of Epstein-Barr virus is more common in young pediatric renal transplant recipients.
- 2020
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Ingår i: Pediatric nephrology. - : Springer Science and Business Media LLC. - 1432-198X .- 0931-041X. ; 35:3, s. 427-439
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Tidskriftsartikel (refereegranskat)abstract
- Epstein-Barr virus (EBV) infections can induce post-transplant lymphoproliferative disorder (PTLD). A chronic high load (CHL), as indicated by long-term high EBV DNA levels after transplantation, has been associated with an enhanced risk of PTLD. We aimed to evaluate incidence, time of occurrence, risk factors, and outcome of EBV CHL carrier state after pediatric renal transplantation.A retrospective study of 58 children aged 1-17 years (median 10), who underwent renal transplantation between January 2004 and June 2017 at a single medical center. EBV IgG antibodies in serum were analyzed before and yearly after transplantation. EBV DNA in whole blood were analyzed weekly for the first 3 months post-transplant, monthly up to 1 year and then at least once yearly. CHL was defined as EBV DNA ≥ 4.2 log10 Geq/ml in > 50% of the samples during ≥ 6 months.At transplantation, 31 (53%) patients lacked EBV IgG and 25 (81%) of them developed primary EBV infection post-transplant. Of the 27 seropositive patients, 20 (74%) experienced reactivation of EBV. Altogether, 14 (24%) children developed CHL, starting at a median of 69 days post-transplant and lasting for a median time of 2.3 years (range 0.5-6.5), despite reduction of immunosuppression. Patients with CHL were younger and 11/14 were EBV seronegative at transplantation. No child developed PTLD during median clinical follow-up of 7.8 years (range 0.7-13).CHL was frequent, long lasting, and occurred mainly in young transplant recipients. The absence of PTLD suggests that monitoring of EBV DNA to guide immunosuppression was effective.
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| 42. |
- Yasinska, Valentyna, et al.
(författare)
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Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids
- 2023
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Ingår i: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure.Methods: Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study.Measurements and main results: The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12–18 months.Conclusion: The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.
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| 43. |
- Zabihipour, Marzieh, et al.
(författare)
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Organic electrochemical transistors manufactured by laser ablation and screen printing
- 2022
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Ingår i: Flexible and Printed Electronics. - : IOP Publishing Ltd. - 2058-8585. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- The dimensions of the material serving as the channel in organic electrochemical transistors (OECTs) are important for the overall switching performance. Here, a laser ablation step is included in the OECT manufacturing process, in an attempt to shorten the channel length of the OECT. The source and drain electrodes are formed by laser ablation of a previously screen printed carbon-based rectangle, which in this study resulted in an average channel length equal to 25 mu m. All other processing steps rely on screen printing, allowing for large-area manufacturing of OECTs and OECT-based circuits on flexible substrates. This approach results in a manufacturing yield of 89%; 178 out of a total of 200 OECTs exhibited an ON/OFF ratio exceeding 1000 with a statistical mean value of 28 000 and reproducible switching performance. OECT-based circuits, here demonstrated by a logic inverter, provide a reasonably high voltage gain of 12. The results thus demonstrate another reliable OECT manufacturing process, based on the combination of laser ablation and screen printing.
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