| 1. |
- Bäck, Tom, 1964, et al.
(författare)
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Targeted alpha therapy with astatine-211-labeled anti-PSCA A11 minibody shows antitumor efficacy in prostate cancer xenografts and bone microtumors
- 2020
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Ingår i: Ejnmmi Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Targeted alpha therapy (TAT) is a promising treatment for micrometastatic and minimal residual cancer. We evaluated systemic alpha-radioimmunotherapy (alpha-RIT) of metastatic castration-resistant prostate cancer (mCRPC) using the alpha-particle emitter At-211-labeled to the anti-PSCA A11 minibody. A11 is specific for prostate stem cell antigen (PSCA), a cell surface glycoprotein which is overexpressed in more than 90% of both localized prostate cancer and bone metastases. Methods PC3-PSCA cells were implanted subcutaneously (s.c.) and intratibially (i.t) in nude mice. Efficacy of alpha-RIT (two fractions-14-day interval) was studied on s.c. macrotumors (0, 1.5 and 1.9 MBq) and on i.t. microtumors (100-200 mu m; 0, 0.8 or 1.5 MBq) by tumor-volume measurements. The injected activities for therapies were estimated from separate biodistribution and myelotoxicity studies. Results Tumor targeting of At-211-A11 was efficient and the effect on s.c. macrotumors was strong and dose-dependent. At 6 weeks, the mean tumor volumes for the treated groups, compared with controls, were reduced by approximately 85%. The separate myelotoxicity study following one single fraction showed reduced white blood cells (WBC) for all treated groups on day 6 after treatment. For the 0.8 and 1.5 MBq, the WBC reductions were transient and followed by recovery at day 13. For 2.4 MBq, a clear toxicity was observed and the mice were sacrificed on day 7. In the long-term follow-up of the 0.8 and 1.5 MBq-groups, blood counts on day 252 were normal and no signs of radiotoxicity observed. Efficacy on i.t. microtumors was evaluated in two experiments. In experiment 1, the tumor-free fraction (TFF) was 95% for both treated groups and significantly different (p < 0.05) from the controls at a TFF of 66%). In experiment 2, the difference in TFF was smaller, 32% for the treated group versus 20% for the controls. However, the difference in microtumor volume in experiment 2 was highly significant, 0.010 +/- 0.003 mm(3) versus 3.79 +/- 1.24 mm(3) (treated versus controls, respectively), i.e., a 99.7% reduction (p < 0.001). The different outcome in experiment 1 and 2 is most likely due to differences in microtumor sizes at therapy, or higher tumor-take in experiment 2 (where more cells were implanted). Conclusion Evaluating fractionated alpha-RIT with At-211-labeled anti-PSCA A11 minibody, we found clear growth inhibition on both macrotumors and intratibial microtumors. For mice treated with multiple fractions, we also observed radiotoxicity manifested by progressive loss in body weight at 30 to 90 days after treatment. Our findings are conceptually promising for a systemic TAT of mCRPC and warrant further investigations of At-211-labeled PSCA-directed vectors. Such studies should include methods to improve the therapeutic window, e.g., by implementing a pretargeted regimen of alpha-RIT or by altering the size of the targeting vector.
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| 2. |
- Cederwall, Bo, et al.
(författare)
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Evidence for a spin-aligned neutron-proton paired phase from the level structure of 92Pd
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 469:7328, s. 68-71
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Tidskriftsartikel (refereegranskat)abstract
- Shell structure and magic numbers in atomic nuclei were generally explained by pioneering work(1) that introduced a strong spin-orbit interaction to the nuclear shell model potential. However, knowledge of nuclear forces and the mechanisms governing the structure of nuclei, in particular far from stability, is still incomplete. In nuclei with equal neutron and proton numbers (N = Z), enhanced correlations arise between neutrons and protons (two distinct types of fermions) that occupy orbitals with the same quantum numbers. Such correlations have been predicted to favour an unusual type of nuclear superfluidity, termed isoscalar neutron-proton pairing(2-6), in addition to normal isovector pairing. Despite many experimental efforts, these predictions have not been confirmed. Here we report the experimental observation of excited states in the N = Z = 46 nucleus Pd-92. Gamma rays emitted following the Ni-58(Ar-36,2n)Pd-92 fusion-evaporation reaction were identified using a combination of state-of-the-art high-resolution c-ray, charged-particle and neutron detector systems. Our results reveal evidence for a spin-aligned, isoscalar neutron-proton coupling scheme, different from the previous prediction(2-6). We suggest that this coupling scheme replaces normal superfluidity (characterized by seniority coupling(7,8)) in the ground and low-lying excited states of the heaviest N = Z nuclei. Such strong, isoscalar neutron-proton correlations would have a considerable impact on the nuclear level structure and possibly influence the dynamics of rapid proton capture in stellar nucleosynthesis.
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| 3. |
- Fransson, Kristin, et al.
(författare)
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Miljöhandbokför upphandlare
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Hållbar utveckling innefattar såväl social, ekonomisk som miljömässig hållbar utveckling.I Miljöhandboken kommer dessa tre aspekter av hållbar utveckling att behandlas,dock ligger störst fokus på miljöaspekterna.Miljöhandboken ska hjälpa upphandlare att ställa relevanta miljökrav vid upphandlingoch är ett komplement till exempelvis Konkurrensverkets (f.d. Miljöstyrningsrådets)upphandlingskriterier och ska bidra med fakta kring hur miljökrav kan ställas.Miljökrav vid upphandling kan innefatta bl. a. energianvändning, livslängd, skadligaämnen, strålning, återvinning och miljöledningssystem. Kravens betydelse påverkasbl. a. av upphandlingens omfattning och miljömognaden inom produktsegmentet. Imiljöhandboken presenteras inga specifika kriterier eller gränsvärden för olika miljöaspekter,i stället ges länkar till exempelvis lagstiftning, myndigheter och miljömärkningar.Detta för att kriterier och gränsvärden uppdateras kontinuerligt som en följdav teknikutveckling men också för att den samlade kunskapen om vad som är miljöproblemständigt växer och kan ge upphov till nya kriterier och gränsvärden. Tyngdpunkteni denna handbok ligger på miljöpåverkan ur ett livscykelperspektiv, vilket innebäratt hänsyn tas till miljöpåverkan från utvinning av råmaterial till resthantering aven produkt.
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| 4. |
- Hadinia, Baharak, et al.
(författare)
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In-beam gamma-ray and alpha-decay spectroscopy of 170Ir
- 2007
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 76:4, s. 044312-1-044312-8
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in the highly neutron deficient odd-odd nucleus Ir-170 have been investigated. The experiment was performed using the Sn-112(Ni-60, pn)Ir-170 reaction and employing the recoil-decay tagging technique. Gamma rays were detected using the JUROGAM gamma-ray spectrometer and those belonging to Ir-170 were selected based on recoil identification provided by the RITU gas-filled recoil separator and the GREAT spectrometer at the RITU focal plane. A partial level scheme of Ir-170 is presented for the first time. New alpha-decay branches are assigned to Ir-170 and a tentative level structure for Re-166 is deduced from a study of the alpha-decay fine structure and the associated alpha-gamma correlations.
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| 5. |
- Sandzelius, Mikael, et al.
(författare)
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First identification of excited states in 169Ir
- 2007
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 75:5, s. 054321-
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Tidskriftsartikel (refereegranskat)abstract
- Gamma rays populating the alpha-decaying isomeric state in Ir-169 have been observed for the first time. The experiment employed the recoil-decay tagging method using the JUROGAM gamma-ray spectrometer, the RITU gas-filled recoil separator and the GREAT spectrometer located at the RITU focal plane. The gamma-ray cascade feeding the isomeric alpha-decaying state exhibits a rotational structure consistent with a h(11/2) proton coupled to a triaxially deformed core. The experimental results are compared with predictions from total Routhian surface calculations.
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| 6. |
- Albertsson, Per, 1964, et al.
(författare)
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Astatine-211 based radionuclide therapy: Current clinical trial landscape
- 2023
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Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Astatine-211 (At-211) has physical properties that make it one of the top candidates for use as a radiation source for alpha particle-based radionuclide therapy, also referred to as targeted alpha therapy (TAT). Here, we summarize the main results of the completed clinical trials, further describe ongoing trials, and discuss future prospects.
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| 7. |
- Andgren, Karin, et al.
(författare)
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gamma-ray spectroscopy of At-197
- 2008
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 78:4, s. 044328-1-044328-8
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Tidskriftsartikel (refereegranskat)abstract
- Excited states of the extremely neutron-deficient nucleus At-197 have been studied in an in-beam experiment using the fusion-evaporation reaction Sn-118(Kr-82,p2n)At-197. gamma rays belonging to At-197 feeding the I-pi=(9/2(-)) ground state, as well as gamma rays feeding the 311-keV I-pi=(13/2(+)) isomer, decaying via the emission of gamma rays, and the 52-keV I-pi=(1/2(+)) alpha-decaying isomer have been identified using the recoil-alpha-decay tagging technique. Total Routhian surface calculations predict a near-spherical shape for the (9/2(-)) ground state and oblate shapes with beta(2) around -0.2 for the (1/2(+)) and the (13/2(+)) states. These predictions agree with our experimental findings.
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| 8. |
- 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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| 9. |
- 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
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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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| 10. |
- Berg, Lisa, et al.
(författare)
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Parental alcohol-related disorders and school performance in 16 year olds - a national cohort study
- 2016
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Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 111:10, s. 1795-1803
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Tidskriftsartikel (refereegranskat)abstract
- To study the links between parental alcohol-related disorders and offspring school performance and, specifically, whether associations vary by gender of parent or child and whether associations are mediated by other adverse psychosocial circumstances commonly appearing together with parental alcohol problems, such as parental mental health problems or criminal behaviour.Register study in a national cohort.SettingSweden.740 618 individuals born in Sweden in 1990-1996.Parental hospital admissions for alcohol-related disorders and school performance in their offspring, in the final year of compulsory school at age 15-16, was analysed in relation to sociodemographic confounders and psychosocial covariates, using linear and logistic regressions.Both mothers’ and fathers’ alcohol-related hospital admissions were associated with lower z-scores of grades and national mathematic tests scores. After adjustment for parental education and sociodemographic confounders, beta-coefficients of z-scores of grades were -0.42 (95% CI -0.45, -0.39) and -0.42 (95 % CI -0.43,-0.40), and beta-coefficients of mathematic tests scores were -0.36 (95% CI -0.39, -0.33) and -0.31 (95% CI -0.33, -0.29), for mothers’ and fathers’ alcohol-related disorders, respectively. Adjusted ORs for not being eligible for secondary school were 1.99 (95% CI 1.84-2.15) and 2.04 (95% CI 1.95-2.15) for mothers’ and fathers’ alcohol-related disorders, respectively. Adjusting the analyses for psychosocial factors in the family almost eradicated the statistical effects of parental alcohol-related disorders on offspring school performance to beta-coefficients of 0.03 to -0.10 and ORs of 0.89 to 1.15. The effect of a mother's alcohol-related hospital admission on school performance was stronger in girls than in boys, whereas no gender differences were seen for a father's alcohol-related hospital admission.ConclusionsIn Sweden, alcohol-related disorders in both mothers and fathers are associated with lower school performance in their children at age 15-16, with most of the statistical effects being attributed to psychosocial circumstances of the family, such as parental psychiatric disorders, drug use, and criminality and receipt of social or child welfare interventions.
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