| 1. |
- Cox, D. M., et al.
(author)
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Spectroscopy along flerovium decay chains. II. Fine structure in odd-A 289Fl
- 2023
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In: Physical Review C. - 2469-9985. ; 107:2
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Journal article (peer-reviewed)abstract
- Fifteen correlated α-decay chains starting from the odd-A superheavy nucleus 289Fl were observed following the fusion-evaporation reaction 48Ca+244Pu. The results call for at least two parallel α-decay sequences starting from at least two different states of 289Fl. This implies that close-lying levels in nuclei along these chains have quite different spin-parity assignments. Further, observed α-electron and α-photon coincidences, as well as the α-decay fine structure along the decay chains, suggest a change in the ground-state spin assignment between 285Cn and 281Ds. Our experimental results, on the excited level structure of the heaviest odd-N nuclei to date, provide a direct testing ground for theory. This is illustrated by comparison with new nuclear structure calculations based on the symmetry-conserving configuration mixing theory.
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| 2. |
- Såmark-Roth, A., et al.
(author)
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Spectroscopy along flerovium decay chains. III. Details on experiment, analysis, 282Cn, and spontaneous fission branches
- 2023
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In: Physical Review C. - 2469-9985. ; 107:2
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Journal article (peer-reviewed)abstract
- Flerovium isotopes (element Z = 114) were produced in the fusion-evaporation reactions 48Ca+242,244Pu and studied with an upgraded TASISpec decay station placed in the focal plane of the gas-filled separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. Twenty-nine flerovium decay chains were identified by means of correlated implantation, α decay, and spontaneous fission events. Data analysis aspects and statistical assessments, primarily based on measured rates of various events, which laid the foundation for the comprehensive spectroscopic information on the flerovium decay chains, are presented in detail. Various decay scenarios of an excited state observed in 282Cn are examined in depth with the help of GEANT4 simulations and assessed by predictions of beyond mean-field calculations including triaxial shape degrees of freedom. Previous, revised, and newly derived fission probabilities of even-even superheavy nuclei are compared with various theoretical predictions.
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| 3. |
- Bousquet, Jean, et al.
(author)
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ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
- 2021
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
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Research review (peer-reviewed)abstract
- Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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| 4. |
- Gaziano, Liam, et al.
(author)
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Mild-to-moderate kidney dysfunction and cardiovascular disease : Observational and mendelian randomization analyses
- 2022
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In: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 146:20, s. 1507-1517
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Journal article (peer-reviewed)abstract
- BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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| 5. |
- Såmark-Roth, Anton, et al.
(author)
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Spectroscopy along flerovium decay chains: Discovery of 280Ds and an excited state in 282Cn
- 2021
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In: Physical Review Letters. - 1079-7114. ; 126:3
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Journal article (peer-reviewed)abstract
- A nuclear spectroscopy experiment was conducted to study α-decay chains stemming from isotopes of flerovium (element Z=114). An upgraded TASISpec decay station was placed behind the gas-filled separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. The fusion-evaporation reactions 48Ca+242Pu and 48Ca+244Pu provided a total of 32 flerovium-candidate decay chains, of which two and eleven were firmly assigned to 286Fl and 288Fl, respectively. A prompt coincidence between a 9.60(1)-MeV α-particle event and a 0.36(1)-MeV conversion electron marked the first observation of an excited state in an even-even isotope of the heaviest man-made elements, namely 282Cn. Spectroscopy of 288Fl decay chains fixed Qα=10.06(1) MeV. In one case, a Qα=9.46(1)-MeV decay from 284Cn into 280Ds was observed, with 280Ds fissioning after only 518 μs. The impact of these findings, aggregated with existing data on decay chains of 286,288Fl, on the size of an anticipated shell gap at proton number Z=114 is discussed in light of predictions from two beyond-mean-field calculations, which take into account triaxial deformation.
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| 6. |
- Tran-Gia, Johannes, et al.
(author)
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On the use of solid 133Ba sources as surrogate for liquid 131I in SPECT/CT calibration : a European multi-centre evaluation
- 2023
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In: EJNMMI Physics. - 2197-7364. ; 10:1
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Journal article (peer-reviewed)abstract
- Introduction: Commissioning, calibration, and quality control procedures for nuclear medicine imaging systems are typically performed using hollow containers filled with radionuclide solutions. This leads to multiple sources of uncertainty, many of which can be overcome by using traceable, sealed, long-lived surrogate sources containing a radionuclide of comparable energies and emission probabilities. This study presents the results of a quantitative SPECT/CT imaging comparison exercise performed within the MRTDosimetry consortium to assess the feasibility of using 133Ba as a surrogate for 131I imaging. Materials and methods: Two sets of four traceable 133Ba sources were produced at two National Metrology Institutes and encapsulated in 3D-printed cylinders (volume range 1.68–107.4 mL). Corresponding hollow cylinders to be filled with liquid 131I and a mounting baseplate for repeatable positioning within a Jaszczak phantom were also produced. A quantitative SPECT/CT imaging comparison exercise was conducted between seven members of the consortium (eight SPECT/CT systems from two major vendors) based on a standardised protocol. Each site had to perform three measurements with the two sets of 133Ba sources and liquid 131I. Results: As anticipated, the 131I pseudo-image calibration factors (cps/MBq) were higher than those for 133Ba for all reconstructions and systems. A site-specific cross-calibration reduced the performance differences between both radionuclides with respect to a cross-calibration based on the ratio of emission probabilities from a median of 12–1.5%. The site-specific cross-calibration method also showed agreement between 133Ba and 131I for all cylinder volumes, which highlights the potential use of 133Ba sources to calculate recovery coefficients for partial volume correction. Conclusion: This comparison exercise demonstrated that traceable solid 133Ba sources can be used as surrogate for liquid 131I imaging. The use of solid surrogate sources could solve the radiation protection problem inherent in the preparation of phantoms with 131I liquid activity solutions as well as reduce the measurement uncertainties in the activity. This is particularly relevant for stability measurements, which have to be carried out at regular intervals.
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| 7. |
- Chen, Hao Yu, et al.
(author)
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Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids With Aortic Stenosis
- 2020
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In: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 5:6, s. 694-702
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Journal article (peer-reviewed)abstract
- Importance: Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets.Objective: To identify novel genetic loci and pathways associated with AS.Design, Setting, and Participants: This genome-wide association study used a case-control design to evaluate 44 703 participants (3469 cases of AS) of self-reported European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (from January 1, 1996, to December 31, 2015). Replication was performed in 7 other cohorts totaling 256 926 participants (5926 cases of AS), with additional analyses performed in 6942 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Follow-up biomarker analyses with aortic valve calcium (AVC) were also performed. Data were analyzed from May 1, 2017, to December 5, 2019.Exposures: Genetic variants (615 643 variants) and polyunsaturated fatty acids (ω-6 and ω-3) measured in blood samples.Main Outcomes and Measures: Aortic stenosis and aortic valve replacement defined by electronic health records, surgical records, or echocardiography and the presence of AVC measured by computed tomography.Results: The mean (SD) age of the 44 703 GERA participants was 69.7 (8.4) years, and 22 019 (49.3%) were men. The rs174547 variant at the FADS1/2 locus was associated with AS (odds ratio [OR] per C allele, 0.88; 95% CI, 0.83-0.93; P = 3.0 × 10-6), with genome-wide significance after meta-analysis with 7 replication cohorts totaling 312 118 individuals (9395 cases of AS) (OR, 0.91; 95% CI, 0.88-0.94; P = 2.5 × 10-8). A consistent association with AVC was also observed (OR, 0.91; 95% CI, 0.83-0.99; P = .03). A higher ratio of arachidonic acid to linoleic acid was associated with AVC (OR per SD of the natural logarithm, 1.19; 95% CI, 1.09-1.30; P = 6.6 × 10-5). In mendelian randomization, increased FADS1 liver expression and arachidonic acid were associated with AS (OR per unit of normalized expression, 1.31 [95% CI, 1.17-1.48; P = 7.4 × 10-6]; OR per 5-percentage point increase in arachidonic acid for AVC, 1.23 [95% CI, 1.01-1.49; P = .04]; OR per 5-percentage point increase in arachidonic acid for AS, 1.08 [95% CI, 1.04-1.13; P = 4.1 × 10-4]).Conclusions and Relevance: Variation at the FADS1/2 locus was associated with AS and AVC. Findings from biomarker measurements and mendelian randomization appear to link ω-6 fatty acid biosynthesis to AS, which may represent a therapeutic target.
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| 8. |
- Chen, H.Y., et al.
(author)
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Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study
- 2023
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In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:21, s. 1927-1939
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Journal article (peer-reviewed)abstract
- Aims Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. Methods and results A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10−8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2–SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26–1.35; P = 2.7 × 10−51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08–1.37; P = 1.4 × 10−3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90–5.12; P = 2.1 × 10−20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17–1.23; P = 4.8 × 10−73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05–1.9; P = 1.9 × 10−12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. Conclusion Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies. © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
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| 9. |
- Kälvemark Sporrong, Sofia, et al.
(author)
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Challenges in qualitative social pharmacy research : Reflections based on a conference workshop
- 2022
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In: Research in Social and Administrative Pharmacy. - : Elsevier. - 1551-7411 .- 1934-8150. ; 18:1, s. 2254-2258
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Journal article (peer-reviewed)abstract
- A methodological debate within social pharmacy is ongoing regarding how to apply a qualitative approach. This paper emanates from a workshop at the Nordic Social Pharmacy Conference in 2019, named 'How do we know it's good? A workshop on quality criteria in qualitative social and clinical pharmacy research', that addressed this debate. The aim of this paper is twofold (1) to present the main key points raised during the workshop and (2) based on these inputs to contribute to the ongoing discussion on qualitative methodology within social pharmacy research. This paper starts with what was discussed at the workshop and further elaborated are some of the challenges with conducting qualitative research within social pharmacy. These include methodological and disciplinary competence and insecurity, reflections on the consequences of that many social pharmacy researchers come from a natural science background and how this (possibly) shapes the practice of qualitative research within the field. For example, how concepts like transparency and saturation, together with checklists and quality criteria are understood and used. Finally, we make suggestions for the next step for qualitative research in social pharmacy.
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| 10. |
- Lindskog, Magnus, et al.
(author)
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Ilixadencel, a Cell-based Immune Primer, plus Sunitinib Versus Sunitinib Alone in Metastatic Renal Cell Carcinoma: A Randomized Phase 2 Study
- 2022
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In: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 40, s. 38-45
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Journal article (peer-reviewed)abstract
- Background: The prognosis of patients with synchronous metastatic renal cell carcinoma (mRCC) is poor. Whereas single-agent tyrosine kinase inhibition (TKI) is clearly insufficient, the effects can be enhanced by combinations with immune checkpoint inhibitors. Innovative treatment options combining TKI and other immune-stimulating agents could prove beneficial. Objective: To evaluate the clinical effects on metastatic disease when two doses of allogeneic monocyte-derived dendritic cells (ilixadencel) are administrated intratumorally followed by nephrectomy and treatment with sunitinib compared with nephrectomy and sunitinib monotherapy, in patients with synchronous mRCC. Design, setting, and participants: A randomized (2:1) phase 2 multicenter trial enrolled 88 patients with newly diagnosed mRCC to treatment with the combination ilixadencel/sunitinib (ILIXA/SUN; 58 patients) or sunitinib alone (SUN; 30 patients).Outcome measurements and statistical analysis: The primary endpoints were 18mo survival rate and overall survival (OS). A secondary endpoint was objective response rate (ORR) assessed up to 18 mo after enrollment. Statistic evaluations included Kaplan-Meier estimates, log-rank tests, Cox regression, and stratified Cochran-Mantel-Haenszel tests.Results and limitations: The median OS was 35.6 mo in the ILIXA/SUN arm versus 25.3 mo in the SUN arm (hazard ratio 0.73, 95% confidence interval 0.42-1.27; p = 0.25), while the 18-mo OS rates were 63% and 66% in the ILIXA/SUN and SUN arms, respectively. The confirmed ORR in the ILIXA/SUN arm were 42.2% (19/45), including three patients with complete response, versus 24.0% (six/25) in the SUN arm (p = 0.13) without complete responses. The study was not adequately powered to detect modest differences in survival. Conclusions: The study failed to meet its primary endpoints. However, ilixadencel in combination with sunitinib was associated with a numerically higher, nonsignificant, confirmed response rate, including complete responses, compared with sunitinib monotherapy.Patient summary: We studied the effects of intratumoral vaccination with ilixadencel followed by sunitinib versus sunitinib only in a randomized phase 2 study. The combination treatment showed numerically higher numbers of confirmed responses, suggesting an immunologic effect.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).
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