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1.
  • 2017
  • swepub:Mat__t
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  • Cox, D. M., et al. (author)
  • Spectroscopy along flerovium decay chains. II. Fine structure in odd-A 289Fl
  • 2023
  • In: Physical Review C. - 2469-9985. ; 107:2
  • 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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  • Såmark-Roth, A., et al. (author)
  • Spectroscopy along flerovium decay chains. III. Details on experiment, analysis, 282Cn, and spontaneous fission branches
  • 2023
  • In: Physical Review C. - 2469-9985. ; 107:2
  • 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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  • Albertsson, Per, 1964, et al. (author)
  • Differential locomotion of long- and short-term IL-2-activated murine natural killer cells in a model matrix environment.
  • 2007
  • In: Scandinavian journal of immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 66:4, s. 402-9
  • Journal article (peer-reviewed)abstract
    • Tumour infiltration by activated natural killer (A-NK) cells is a pre-requisite for tumour eradication by adoptive NK cell transfer. Extravasated A-NK cells do not always succeed in reaching the crucial target cell conjugation. Therefore, we wished to study A-NK cell locomotion and interactions with melanoma cells in a matrix environment (Matrigel) by electron, confocal and fluorescence microscopy. Two distinct patterns of A-NK cell-mediated matrix disintegration were revealed during incubation of tumour cells and A-NK cells in Matrigel: (1) A-NK cells pre-cultured for 5 days altered the homogeneous texture of the Matrigel, an initial microporous appearance became a loose filamentous meshwork by 24 h. Matrix degrading protease inhibitors could not fully prevent this, but could delay the process; and (2) A-NK cells pre-cultured for 6 days or more, instead formed large excavations in the Matrigel leaving the remaining matrix less affected compared to the effects by the younger A-NK cells. By histochemical staining with Cupromeronic Blue, the excavations were shown to contain proteoglycan material. Protease inhibitors had no discernable effect on the development of the excavations. The conspicuous capacity of A-NK cells to disintegrate extracellular matrix and the formation of large excavations seems only partially to depend on matrix-degrading proteases. Formation of extracellular proteoglycan material is suggested to facilitate A-NK cell locomotion within a matrix environment.
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  • Delewi, Ronak, et al. (author)
  • Clinical and Procedural Characteristics Associated With Higher Radiation Exposure During Percutaneous Coronary Interventions and Coronary Angiography.
  • 2013
  • In: Circulation. Cardiovascular interventions. - 1941-7632. ; 6, s. 501-506
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: WE AIM TO STUDY THE CLINICAL AND PROCEDURAL CHARACTERISTICS ASSOCIATED WITH HIGHER RADIATION EXPOSURE IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTIONS (PCIS) AND CORONARY ANGIOGRAPHY.METHODS AND RESULTS: OUR PRESENT STUDY INCLUDED ALL CORONARY ANGIOGRAPHY AND PCI PROCEDURES IN 5 PCI CENTERS IN THE WESTERN PART OF SWEDEN, BETWEEN JANUARY 1, 2008, AND JANUARY 19, 2012. THE RADIATION EXPOSURE AND CLINICAL DATA WERE COLLECTED PROSPECTIVELY IN THESE 5 PCI CENTERS IN SWEDEN AS PART OF THE SWEDISH CORONARY ANGIOGRAPHY AND ANGIOPLASTY REGISTRY (SCAAR). A PREDICTION MODEL WAS MADE FOR THE RADIATION EXPOSURE (DOSEAREA PRODUCT) EXPRESSED IN GYCM(2). A TOTAL OF 20 669 PROCEDURES WERE INCLUDED IN THE PRESENT STUDY, CONSISTING OF 9850 PCI AND 10 819 CORONARY ANGIOGRAPHY PROCEDURES. IN MULTIVARIABLE ANALYSES, BODY MASS INDEX (=1.04; CONFIDENCE INTERVAL [CI], 1.041.04; P0.001); HISTORY OF CORONARY ARTERY BYPASS GRAFT SURGERY (=1.32; CI, 1.281.32; P0.001); 2, 3, OR 4 TREATED LESIONS (2 TREATED LESIONS: =1.95; CI, 1.842.03; P0.001; 3 TREATED LESIONS: =2.34; CI, 2.162.53; P0.001; AND 4 TREATED LESIONS: =2.83; CI, 2.533.16; P0.001); AND CHRONIC TOTAL OCCLUSION LESIONS (=1.39; CI, 1.311.48; P0.001) WERE ASSOCIATED WITH THE HIGHEST RADIATION EXPOSURE. AFTER ADJUSTING FOR PROCEDURAL COMPLEXITY, RADIAL ACCESS ROUTE WAS NOT ASSOCIATED WITH INCREASED RADIATION EXPOSURE (=1.00; CI, 0.981.03; P=0.67).CONCLUSIONS: In the largest study population to assess radiation exposure, we found that high body mass index, history of coronary artery bypass graft surgery, number of treated lesions, and chronic total occlusions were associated with the highest patient radiation exposure. Radial access site was not associated with higher radiation exposure when compared with femoral approach.
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  • Glimelius, Bengt, et al. (author)
  • A randomized phase III multicenter trial comparing irinotecan in combination with the Nordic bolus 5-FU and folinic acid schedule or the bolus/infused de Gramont schedule (Lv5FU2) in patients with metastatic colorectal cancer
  • 2008
  • In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 19:5, s. 909-914
  • Journal article (peer-reviewed)abstract
    • Background: To compare irinotecan with the Nordic 5-fluorouracil (5-FU) and folinic acid (FA) bolus schedule [irinotecan 180 mg/m2 on day 1, 5-FU 500 mg/m2 and FA 60 mg/m2 on day 1 and 2 (FLIRI)] or the Lv5FU2 schedule [irinotecan 180 mg/m2 on day 1, FA 200 mg/m2, 5-FU bolus 400 mg/m2 and infused 5-FU 600 mg/m2 on day 1 and 2 (Lv5FU2-IRI)] due to uncertainties about how to administrate 5-FU with irinotecan. Patients and methods: Patients (n = 567) with metastatic colorectal cancer were randomly assigned to receive FLIRI or Lv5FU2-IRI. Primary end point was progression-free survival (PFS). Results: Patient characteristics were well balanced. PFS did not differ between groups (median 9 months, P = 0.22). Overall survival (OS) was also similar (median 19 months, P = 0.9). Fewer objective responses were seen in the FLIRI group (35% versus 49%, P = 0.001) but the metastatic resection rate did not differ (4% versus 6%, P = 0.3). Grade 3/4 neutropenia (11% versus 5%, P = 0.01) and grade 2 alopecia (18% versus 9%, P = 0.002) were more common in the FLIRI group. The 60-day mortality was 2.4% versus 2.1%. Conclusions: Irinotecan with the bolus Nordic schedule (FLIRI) is a convenient treatment with PFS and OS comparable to irinotecan with the Lv5FU2 schedule. Neutropenia and alopecia are more prevalent, but both regimens are equally well tolerated. © The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
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  • Maghnie, M., et al. (author)
  • Safety and Efficacy of Pediatric Growth Hormone Therapy: Results From the Full KIGS Cohort
  • 2022
  • In: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:12, s. 3287-3301
  • Journal article (peer-reviewed)abstract
    • Context The Kabi/Pfizer International Growth Database (KIGS) is a large, international database (1987-2012) of children treated with recombinant human growth hormone (rhGH) in real-world settings. Objective This work aimed to evaluate the safety and efficacy of rhGH from the full KIGS cohort. Methods Data were collected by investigators from children with growth disorders treated with rhGH (Genotropin [somatropin]; Pfizer). Safety was evaluated in all treated patients, and efficacy in those treated for 1 year or more. A subgroup included patients treated for 5 years or more (>= 2 years prepubertal) who had reached near-adult height (NAH). Main outcomes included adverse events (AEs), serious AEs (SAEs), and height growth. Results The full KIGS cohort (N = 83 803 [58% male]) was treated for idiopathic GH deficiency (IGHD; 46.9%), organic GHD (10.0%), small for gestational age (SGA; 9.5%), Turner syndrome (TS; 9.2%), idiopathic short stature (ISS; 8.2%), and others (16.2%). Median rhGH treatment duration was 2.7 years and observation 3.1 years. SAEs occurred in 3.7% of patients and death in 0.4%. The most common SAEs were recurrence of craniopharyngioma (n = 151), neoplasm (n = 99), and cancer (n = 91); and scoliosis (n = 91). Median first-year delta height-SD score (SDS) (Prader) in prepubertal patients was 0.66 (IGHD), 0.55 (ISS), 0.58 (TS), and 0.71 (SGA). Median gains in NAH-SDS were 1.79 (IGHD), 1.37 (ISS), and 1.34 (SGA) for boys, and 2.07 (IGHD), 1.62 (ISS), 1.07 (TS), and 1.57 (SGA) for girls. Conclusion Data from KIGS, the largest and longest running international database of rhGH-treated children, show that rhGH is safe and increases short-term height gain and adult height across GHD and non-GHD conditions.
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  • Råmunddal, Truls, et al. (author)
  • Prognostic Impact of Chronic Total Occlusions : A Report From SCAAR (Swedish Coronary Angiography and Angioplasty Registry)
  • 2016
  • In: JACC: Cardiovascular Interventions. - : Elsevier BV. - 1936-8798. ; 9:15, s. 1535-1544
  • Journal article (peer-reviewed)abstract
    • Objectives The aim of this study was to determine the prognostic impact of chronic total occlusion (CTO) on long-term mortality in a large prospective cohort. Background CTO is present in many patients with coronary artery disease and is difficult to treat with percutaneous coronary intervention. Methods The study population consisted of all consecutive patients who underwent coronary angiography in Sweden between January 1, 2005 and January 1, 2012, who were registered in SCAAR (Swedish Coronary Angiography and Angioplasty Registry). The patient population was heterogeneous with regard to indication for angiography (stable angina, ST-segment elevation myocardial infarction [STEMI], unstable angina or non-STEMI, and other) and treatment options. The long-term mortality rates of patients with and without CTO were compared by using shared frailty Cox proportional hazards regression adjusted for confounders. Tests were conducted for interactions between CTO and several pre-specified characteristics: indication for angiography and percutaneous coronary intervention (stable angina, STEMI, unstable angina or non-STEMI, and other), severity of coronary artery disease (1-, 2-, and 3-vessel and/or left main coronary artery disease), age, sex, and diabetes. Results During the study period, 14,441 patients with CTO and 75,431 patients without CTO were registered in SCAAR. CTO was associated with higher mortality (hazard ratio: 1.29; 95% confidence interval: 1.22 to 1.37; p < 0.001). In subgroup analyses, the risk attributable to CTO was lowest in patients with stable angina and highest in those with STEMI. In addition, CTO was associated with highest risk in patients under 60 years of age and with lowest risk in octogenarians. There was no interaction between CTO and either diabetes or sex, suggesting an equally adverse effect in both groups. Conclusions In this large prospective observational study of patients with coronary artery disease, CTO was associated with increased mortality. This association was most prominent in younger patients and in those with acute coronary syndromes.
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  • Såmark-Roth, Anton, et al. (author)
  • Spectroscopy along flerovium decay chains: Discovery of 280Ds and an excited state in 282Cn
  • 2021
  • In: Physical Review Letters. - 1079-7114. ; 126:3
  • 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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  • Wit, J M., et al. (author)
  • Personalized Approach to Growth Hormone Treatment: Clinical Use of Growth Prediction Models
  • 2013
  • In: Hormone Research in Paediatrics. - : Karger. - 1663-2818 .- 1663-2826. ; 79:5, s. 257-270
  • Research review (peer-reviewed)abstract
    • The goal of growth hormone (GH) treatment in a short child is to attain a fast catch-up growth toward the target height (TH) standard deviation score (SDS), followed by a maintenance phase, a proper pubertal height gain, and an adult height close to TH. The short-term response variable of GH treatment, first-year height velocity (HV) (cm/year or change in height SDS), can either be compared with GH response charts for diagnosis, age and gender, or with predicted HV based on prediction models. Three types of prediction models have been described: the Kabi International Growth Hormone Study models, the Gothenburg models and the Cologne model. With these models, 50-80% of the variance could be explained. When used prospectively, individualized dosing reduces the variation in growth response in comparison with a fixed dose per body weight. Insulin-like growth factor-I-based dose titration also led to a decrease in the variation. It is uncertain whether adding biochemical, genetic or proteomic markers may improve the accuracy of the prediction. Prediction models may lead to a more evidence-based approach to determine the GH dose regimen and may reduce the drug costs for GH treatment. There is a need for user-friendly software programs to make prediction models easily available in the clinic.
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  • Yang, Q., et al. (author)
  • Morphological appearance, content of extracellular matrix and vascular density of lung metastases predicts permissiveness to infiltration by adoptively transferred natural killer and T cells.
  • 2006
  • In: Cancer immunology, immunotherapy : CII. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 55:6, s. 699-707
  • Journal article (peer-reviewed)abstract
    • We have recently shown that adoptively transferred, IL-2-activated natural killer (A-NK) cells are able to eliminate well-established B16-F10.P1 melanoma lung metastases. However, some B16-F10.P1 lung metastases were resistant to infiltration by the A-NK cells and also resistant to the A-NK cell treatment. The infiltration-resistant (I-R) B16-F10.P1 metastases had a unique "compact" morphology compared to the "loose" morphology of the infiltration-permissive (I-P) metastases. Here, we show that I-P loose tumors and I-R compact tumors are also found in lung metastases of mouse Lewis lung carcinoma (3LL), MCA-102 sarcoma, and MC38 colon carcinoma as well as rat MADB106 mammary carcinoma origin. Furthermore, the infiltration resistance of the compact tumors is not restricted to A-NK cells, since PHA and IL-2 stimulated CD8+ T-cells (T-LAK cells) also infiltrated the compact tumors poorly. Analyses of tumors for extracellular matrix (ECM) components and PECAM-1(+) vasculature, revealed that the I-R lesions are hypovascularized and contain very little laminin, collagen and fibronectin. In contrast, the I-P loose tumors are well-vascularized and they contain high amounts of ECM components. Interestingly, the distribution pattern of ECM components in the I-P loose tumors is almost identical to that of the normal lung tissue, indicating that these tumors develop around the alveolar walls which provide the loose tumors with both a supporting tissue and a rich blood supply. In conclusion, tumor infiltration by activated NK and T cells correlates with the presence of ECM components and PECAM-1(+) vasculature in the malignant tissue. Thus, analysis of the distribution of ECM and vasculature in tumor biopsies may help select patients most likely to benefit from cellular adoptive immunotherapy.
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  • Aberg, S., et al. (author)
  • Nuclear Structure Effects in Fission
  • 2023. - 1
  • In: Journal of Physics: Conference Series. - 1742-6588. ; 2586
  • Conference paper (peer-reviewed)abstract
    • Three examples of nuclear structure effects in fission dynamics are discussed: (i) The appearance of a super-short symmetric mode in the fission of nuclei around 264Fm leading to two double-magic 132Sn, (ii) Fission of some super-heavy elements where the heavy cluster is focused around double-magic 208Pb, and (iii) A saw-tooth distribution in angular momenta versus the fission fragment mass in the fission of 239U. The Metropolis random walk method is used to simulate the strongly damped fission dynamics on a 5D deformation grid. The dynamics is driven by pairing-, shape- and energy-dependent level densities. When available, a good agreement with experimental data is obtained.
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  • Albertsson, Eva, 1979, et al. (author)
  • Marin fiskodling på den svenska västkusten: Biologiska förutsättningar : Rapport nummer 1 från Vattenbrukscentrum Väst, Göteborgs universitet
  • 2013
  • Reports (other academic/artistic)abstract
    • I den av regeringen beställda utredningen ”Det växande Vattenbrukslandet” föreslås att ”Göteborgs universitet (GU) tillförs resurser för att fortsätta att utveckla vattenbruksrelaterad forskning när det gäller musslor, ostron och marina fiskarter”. Därför tog under 2011 företrädare inom den odlingsrelaterade fiskforskningen vid Gö- teborgs universitet initiativet till denna studie om förutsättningarna för marin fiskodling. Studien har syftet att utreda de odlingsbiologiska förutsättningarna för etablering av vattenbruk av marina fiskarter på den svenska västkusten. Målet är att den ska kunna användas som kunskapsunderlag för en framtida handlingsplan för fiskodling på västkusten, och främja kunskapsutbytet mellan den fiskodlingsrelaterade forskningen, beslutsfat- tande organ och privata entreprenörer för att utveckla konkurrenskraftiga innovationer inom vattenbruket. En central fråga för sammanhanget är vilka fiskarter det finns potential för att odla på den svenska västkusten. Vattenbruket måste vara ekonomiskt bärkraftigt och en urvalsmodell baserad på svenska marina fiskarters kg- pris i förhållande till en minsta tänkbara produktionskostnad användes därför i denna studie. Vidare bedöm- des arterna utifrån kunskapsläge och odlingspotential. Arterna hälleflundra, tunga, piggvar, havskatt (vanlig och fläckig) samt lyrtorsk och torsk bedömdes att vara ”kandidatarter” för framtida odling i Sverige. För dessa arter gjordes omfattande studier för att vidare utreda behov och möjligheter. Det gjordes även en analys av de abiotiska faktorerna (vattentemperatur, syrgas- och salthalt) på den svenska västkusten. I en sista del av studien kombinerades kunskapen om kandidatarternas biologiska förutsättningar med västkustens abiotiska faktorer. De abiotiska förhållandena på den svenska västkusten är inte odlingsbiologiskt optimala för traditionell nät- kasseodling för någon av de framtagna kandidatarterna, då för höga sommartemperaturer skapar problem för kallvattensarterna medan varmvattensarterna hämmas av de låga vintertemperaturerna. En av de huvudsak- liga slutsatserna i denna rapport är därför att året-runt-bedriven fiskodling i öppna system, såsom i kustnära nätkassar, knappast är praktiskt genomförbart på den svenska västkusten för de arter som i denna studie i övrigt ansågs ha hög odlingspotential. För etablering av framgångsrika odlingssystem behövs speciella tekniska lösningar, som möjliggör reglering av abiotiska faktorer såsom syrgashalter och temperatur. För att Sverige skall kunna bli ett växande vattenbruksland krävs samordnade insatser mellan forskare från flera discipliner, privata aktörer och andra intressenter. Dessutom krävs satsningar på forskning och utredning av de mera tekniskt avancerade odlingssystem som den svenska västkusten kommer behöva. Med tanke på miljöbelastningsproblematiken kring öppna havsbaserade system för fiskodling samt de abiotiska faktorerna längs västkusten som inte är optimala för någon av kandidatarterna i utredningen, så är slutsatsen att man bör undersöka, alternativa odlingssystem till traditionella öppna nätkassar för fiskodling, där man kan kontrollera faktorer som temperatur, salthalt och syrenivåer och minimera utsläppen. Nästa steg som föreslås är att göra en teknisk/ekonomisk utredning kring hållbara havs- eller landbaserade system för marin fiskodling. Utred- ningen bör innehålla fall-studier för en eller två fiskarter och ett kräftdjur och inkludera en myndighetspröv- ning för de framtagna koncepten. Ytterligare en förutsättning för att vattenbruket skall kunna utvecklas är satsningar på nödvändig infrastruktur, som ett marint kläckeri för forskning och utvecklingsarbete.
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  • Albertsson-Karlgren, U, et al. (author)
  • Mental disease postpartum: Maternal expectations of and maternal reports of infant temperament
  • 1999
  • In: NORDIC JOURNAL OF PSYCHIATRY. - : SCANDINAVIAN UNIVERSITY PRESS. - 0803-9488. ; 53:4, s. 267-274
  • Journal article (peer-reviewed)abstract
    • In a longitudinal study 14 mentally ill women were compared with a control sample of 24 somatically ill women. Both samples were admitted to the hospital within 6 months after delivery. Another control sample of 76 healthy women was included in the study
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  • Albertsson, M., et al. (author)
  • Correlation studies of fission-fragment neutron multiplicities
  • 2021
  • In: Physical Review C. - 2469-9985. ; 103:1
  • Journal article (peer-reviewed)abstract
    • We calculate neutron multiplicities from fission fragments with specified mass numbers for events having a specified total fragment kinetic energy. The shape evolution from the initial compound nucleus to the scission configurations is obtained with the metropolis walk method on the five-dimensional potential-energy landscape, calculated with the macroscopic-microscopic method for the three-quadratic-surface shape family. Shape-dependent microscopic level densities are used to guide the random walk, to partition the intrinsic excitation energy between the two proto-fragments at scission, and to determine the number of neutrons evaporated from the fragments. The contribution to the total excitation energy of the resulting fragments from statistical excitation and shape distortion at scission is studied. Good agreement is obtained with available experimental data on neutron multiplicities in correlation with fission fragments from U235(nth,f). With increasing neutron energy a superlong fission mode grows increasingly prominent, which affects the dependence of the observables on the total fragment kinetic energy.
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  • Albertsson, M., et al. (author)
  • Excitation energy partition in fission
  • 2020
  • In: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 803
  • Journal article (peer-reviewed)abstract
    • The transformation of an atomic nucleus into two excited fission fragments is modeled as a strongly damped evolution of the nuclear shape. As in previous studies, it is assumed that the division of mass and charge is frozen in at a critical neck radius of c0=2.5fm. In order to also determine the energetics, we follow the system further until scission occurs at a smaller neck radius, at which point the shapes of the proto-fragments are extracted. The statistical energy available at scission is then divided on the basis of the respective microscopic level densities. This approach takes account of important (and energy-dependent) finite-size effects. After the fragments have been fully accelerated and their shapes have relaxed to their equilibrium forms, they undergo sequential neutron evaporation. The dependence of the resulting mean neutron multiplicity on the fragment mass, ν¯(A), including the dependence on the initial excitation energy of the fissioning compound nucleus, agrees reasonably well with observations, as demonstrated here for 235U(n, f), and the sawtooth appearance of ν¯(A) can be understood from shell-structure effects in the level densities.
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  • Albertsson, M., et al. (author)
  • Super-short fission mode in fermium isotopes
  • 2021
  • In: Physical Review C. - 2469-9985. ; 104:6
  • Journal article (peer-reviewed)abstract
    • The so-called super-short fission mode, in which a nucleus divides nearly symmetrically into two unusually energetic fragments, competes favorably with the standard asymmetric fission mode for spontaneous fission of a limited number of nuclei near Fm264 but it quickly fades away at finite excitations. We investigate the energy-dependent competition between those two fission modes for even fermium isotopes from Fm254 to Fm268, using the Metropolis method to simulate the strongly damped fission dynamics being driven by shape- and energy-dependent level densities. The origin of the super-short mode is discussed and its effects on the fragment mass distribution, the total fragment kinetic energy, and the neutron multiplicity are calculated. Generally good agreement with the available data is obtained.
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  • Barnes, A. T., et al. (author)
  • LEGO - II. A 3mm molecular line study covering 100 pc of one of the most actively star-forming portions within the Milky Way disc
  • 2020
  • In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 497:2, s. 1972-2001
  • Journal article (peer-reviewed)abstract
    • The current generation of (sub)mm-telescopes has allowed molecular line emission to become a major tool for studying the physical, kinematic, and chemical properties of extragalactic systems, yet exploiting these observations requires a detailed understanding of where emission lines originate within the Milky Way. In this paper, we present 60'' (similar to 3pc) resolution observations of many 3mm-band molecular lines across a large map of the W49 massive star-forming region (similar to 100x100pc at 11kpc), which were taken as part of the 'LEGO' IRAM-30m large project. We find that the spatial extent or brightness of the molecular line transitions are not well correlated with their critical densities, highlighting abundance and optical depth must be considered when estimating line emission characteristics. We explore how the total emission and emission efficiency (i.e. line brightness per H-2 column density) of the line emission vary as a function of molecular hydrogen column density and dust temperature. We find that there is not a single region of this parameter space responsible for the brightest and most efficiently emitting gas for all species. For example, we find that the HCN transition shows high emission efficiency at high column density (10(22)cm(-2)) and moderate temperatures (35K), whilst e.g. N2H+ emits most efficiently towards lower temperatures (10(22)cm(-2); <20K). We determine XCO(1-0)similar to 0.3 x 10(20)cm(-2)(Kkms(-1))(-1), and alpha(HCN(1-0))similar to 30M(circle dot)(Kkms(-1)pc(2))(-1), which both differ significantly from the commonly adopted values. In all, these results suggest caution should be taken when interpreting molecular line emission.
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  • Blair, J. C., et al. (author)
  • Standard and low-dose IGF-I generation tests and spontaneous growth hormone secretion in children with idiopathic short stature
  • 2004
  • In: Clin Endocrinol (Oxf). ; 60:2, s. 163-8
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Abnormalities in the GH-IGF-I axis, consistent with GH insensitivity (GHI), have been reported in some patients with idiopathic short stature (ISS). The standard IGF-I generation test (IGFGT) has not demonstrated mild GHI in subjects with ISS. The aim of this study was to investigate the GH-IGF-I axis in ISS by performing standard and novel low-dose IGFGTs together with determination of spontaneous GH secretion. PATIENTS AND METHODS: Twenty-one (17 male) prepubertal children with ISS, mean age 8.3 years (4.5-12.2), mean height -3.48 SD (-5.40 to -1.79), mean peak GH to provocation with glucagon/clonidine 32.3 mU/l (14.1-66.0) were studied. Serum IGF-I and IGFBP-3 levels were measured during standard (GH 0.033 mg/kg/day x 4) and low (GH 0.011 mg/kg/day x 4) dose IGFGTs at 0, 12, 36 and 84 h. The low-dose IGFGT was performed in seven naive GH-deficient patients (4 male), mean age 8.5 years (range 4.1-11.1). Determination of spontaneous 24-h GH secretion was performed in the 21 ISS patients. RESULTS: Basal IGF-I and IGFBP-3 standard deviation scores (SDS) in ISS patients were -1.39 (-2.4-1.16) and -0.45 (-1.13-0.38), respectively, IGF-I being lower than IGFBP-3 (P < 0.0001). IGF-I increased in the standard IGFGT at 12 h (P < 0.005), 36 h (P < 0.001) and 84 h (P < 0.001); maximal increment 1.54 (-0.32-3.48), and in the low-dose test at 12 h (P < 0.005), 36 h (P < 0.001) and 84 h (P < 0.005); maximal increment 0.53 (0.08 to -1.23). IGFBP-3 SDS increased in the standard IGFGT at 36 h (P < 0.01) and 84 h (P < 0.001); maximal increment 0.72 (-0.44-1.96), and in the low-dose test at 84 h (P < 0.005); maximal increment 0.33 (-0.08-0.87). Five/19 patients with an IGF-I response > 2 x coefficient of variation (CV) of assay in the standard test failed to respond in the low-dose test, suggestive of mild GHI. In GH-deficient patients, IGF-I increased at each time point (P < 0.05) and IGFBP-3 at 36 h (P < 0.05). Mean GH secretion, expressed in SDS, compared with 66 normal stature controls was: basal GH -0.48 (-0.84-0.93), height of GH peaks compared with zero -0.36 (-1.26-1.51) (both P < 0.05), total GH secretion -0.76 (-1.22-0.42), total GH secretion above baseline -0.67 (-1.21-0.94) (both P < 0.01). CONCLUSIONS: In children with ISS, basal IGF-I and IGFBP-3 SDS values were below the mean, IGF-I showing a greater response in both IGFGTs. In the standard IGFGT, the IGF-I increase at 36 h was equal to that at 84 h. The low-dose IGFGT, in combination with the standard test, may identify patients with mild GHI.
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47.
  • Bäck, Tom, 1964, et al. (author)
  • Targeted alpha therapy with astatine-211-labeled anti-PSCA A11 minibody shows antitumor efficacy in prostate cancer xenografts and bone microtumors
  • 2020
  • In: Ejnmmi Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 10:1
  • Journal article (peer-reviewed)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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48.
  • Craig, M. E., et al. (author)
  • Growth hormone treatment and adverse events in Prader-Willi syndrome: data from KIGS (the Pfizer International Growth Database)
  • 2006
  • In: Clin Endocrinol (Oxf). ; 65:2, s. 178-85
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To evaluate the response to recombinant GH treatment and adverse events in children with Prader-Willi syndrome (PWS) from KIGS, the Pfizer International Growth Database. PATIENTS: A total of 328 children (274 prepubertal, median age 6.0 years; 54 pubertal, median age 12.7 years) were treated for 1 year and 161 children were treated for 2 years with GH. RESULTS: Height standard deviation score (SDS) increased significantly during treatment; the response was greater in prepubertal (-0.7 vs.-1.8 pretreatment) compared with pubertal children (-1.5 vs.-1.8). Predictors of first-year height velocity in multiple regression analysis were GH dose, body weight (positively correlated), height SDS minus mid-parental height SDS and chronological age (negatively correlated), together accounting for 39% of the variation in response to GH. Body mass index (BMI) SDS did not change significantly during 2 years of treatment. Of all the 675 GH-treated PWS patients in KIGS, there were five cases of sudden death (age range 3-15 years). Three were obese (weight for height > 200%) and causes of death included bronchopneumonia, respiratory insufficiency and sleep apnoea. Scoliosis was the most commonly reported adverse event (n = 24), four children developed hyperglycaemia and six had presumptive diabetes (type 2 in five, and one case of type 1). CONCLUSIONS: Short-term growth improved in response to conventional doses of GH in children with PWS. Prior to commencement of GH, examination of the upper airways and sleep studies should be performed in PWS patients. GH should be used with caution in those with extreme obesity or disordered breathing and all patients should be closely monitored for adverse events.
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49.
  • Dauber, A., et al. (author)
  • A Genome-Wide Pharmacogenetic Study of Growth Hormone Responsiveness
  • 2020
  • In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 105:10, s. 3203-3214
  • Journal article (peer-reviewed)abstract
    • CONTEXT: Individual patients vary in their response to growth hormone (GH). No large-scale genome-wide studies have looked for genetic predictors of GH responsiveness. OBJECTIVE: To identify genetic variants associated with GH responsiveness. DESIGN: Genome-wide association study (GWAS). SETTING: Cohorts from multiple academic centers and a clinical trial. PATIENTS: A total of 614 individuals from 5 short stature cohorts receiving GH: 297 with idiopathic short stature, 276 with isolated GH deficiency, and 65 born small for gestational age. INTERVENTION: Association of more than 2 million variants was tested. MAIN OUTCOME MEASURES: Primary analysis: individual single nucleotide polymorphism (SNP) association with first-year change in height standard deviation scores. Secondary analyses: SNP associations in clinical subgroups adjusted for clinical variables; association of polygenic score calculated from 697 genome-wide significant height SNPs with GH responsiveness. RESULTS: No common variant associations reached genome-wide significance in the primary analysis. The strongest suggestive signals were found near the B4GALT4 and TBCE genes. After meta-analysis including replication data, signals at several loci reached or retained genome-wide significance in secondary analyses, including variants near ST3GAL6. There was no significant association with variants previously reported to be associated with GH response nor with a polygenic predicted height score. CONCLUSIONS: We performed the largest GWAS of GH responsiveness to date. We identified 2 loci with a suggestive effect on GH responsiveness in our primary analysis and several genome-wide significant associations in secondary analyses that require further replication. Our results are consistent with a polygenic component to GH responsiveness, likely distinct from the genetic regulators of adult height. © Endocrine Society 2020.
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