| 1. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 3. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 5. |
- Adlarson, Patrik, et al.
(författare)
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ABC effect and resonance structure in the double-pionic fusion to He-3
- 2015
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 91:1, s. 015201-
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Tidskriftsartikel (refereegranskat)abstract
- Exclusive and kinematically complete measurements of the double pionic fusion to He-3 have been performed in the energy region of the so-called ABC effect, which denotes a pronounced low-mass enhancement in the pi pi-invariant mass spectrum. The experiments were carried out with the WASA detector setup at COSY (the cooler synchrotron at Forschungszentrum Julich). Similar to the observations in the basic pn -> d pi(0)pi(0) reaction and in the dd -> He-4 pi(0)pi(0) reaction, the data reveal a correlation between the ABC effect and a resonance-like energy dependence in the total cross section. Differential cross sections are well described by the hypothesis of d* resonance formation during the reaction process in addition to the conventional t-channel Delta Delta mechanism. The deduced d* resonance width can be understood from collision broadening due to Fermi motion of the nucleons in initial and final nuclei.
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| 6. |
- Adlarson, Patrik, et al.
(författare)
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Charge symmetry breaking in dd -> He-4 pi(0) with WASA-at-COSY
- 2014
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 739, s. 44-49
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Tidskriftsartikel (refereegranskat)abstract
- Charge symmetry breaking (CSB) observables are a suitable experimental tool to examine effects induced by quark masses on the nuclear level. Previous high precision data from TRIUMF and IUCF are currently used to develop a consistent description of CSB within the framework of chiral perturbation theory. In this work the experimental studies on the reaction dd -> He-4 pi(0) have been extended towards higher excess energies in order to provide information on the contribution of p-waves in the final state. For this, an exclusive measurement has been carried out at a beam momentum of p(d) = 1.2GeV/c using the WASA-at-COSY facility. The total cross section amounts to sigma(tot) =(118 +/- 18(stat) +/- 13(sys) +/- 8(ext)) p band first data on the differential cross section are consistent with s-wave pion production.
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| 7. |
- Adlarson, Patrik, et al.
(författare)
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Cross section ratio and angular distributions of the reaction p + d -> He-3 + eta at 48.8MeV and 59.8MeV excess energy
- 2014
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 50:6, s. 100-
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Tidskriftsartikel (refereegranskat)abstract
- We present new data for angular distributions and on the cross section ratio of the p+d -> He-3+eta reaction at excess energies of Q - 48.8MeV and Q - 59.8 MeV. The data have been obtained at the WASA-at-COSY experiment (Forschungszentrum Julich) using a proton beam and a deuterium pellet target. While the shape of obtained angular distributions show only a slow variation with the energy, the new results indicate a distinct and unexpected total cross section fluctuation between Q = 20MeV and Q = 60 MeV, which might indicate the variation of the production mechanism within this energy interval.
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| 8. |
- Adlarson, Patrik, et al.
(författare)
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Investigation of the dd -> (3)Hen pi(0) reaction with the FZ Julich WASA-at-COSY facility
- 2013
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 88:1, s. 014004-
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Tidskriftsartikel (refereegranskat)abstract
- An exclusive measurement of the dd -> (3)Hen pi(0) reaction was carried out at a beam momentum of p(d) = 1.2 GeV/c using the WASA-at-COSY facility. Information on the total cross section as well as differential distributions was obtained. The data are described by a phenomenological approach based on a combination of a quasifree model and a partial wave expansion for the three-body reaction. The total cross section is found to be sigma(tot) = ( 2.89 +/- 0.01(stat) +/- 0.06(sys) +/- 0.29(norm)) mu b. The contribution of the quasifree processes ( with the beam or target neutron being a spectator) accounts for 38% of the total cross section and dominates the differential distributions in specific regions of phase space. The remaining part of the cross section can be described by a partial wave decomposition indicating the significance of p-wave contributions in the final state.
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| 9. |
- Adlarson, P., et al.
(författare)
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Isospin decomposition of the basic double-pionic fusion in the region of the ABC effect
- 2013
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 721:4-5, s. 229-236
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Tidskriftsartikel (refereegranskat)abstract
- Exclusive and kinematically complete high-statistics measurements of the basic double-pionic fusion reactions pn -> d pi(0)pi(0), pn -> d pi(+)pi(-) and pp -> d pi(+)pi(0) have been carried out simultaneously over the energy region of the ABC effect using the WASA detector setup at COSY. Whereas the isoscalar reaction part given by the d pi(0)pi(0) channel exhibits the ABC effect, i.e. a low-mass enhancement in the pi pi-invariant mass distribution, as well as the associated resonance structure in the total cross section, the isovector part given by the d pi(+)pi(0) channel shows a smooth behavior consistent with the conventional t-channel Delta Delta process. The d pi(+)pi(-) data are very well reproduced by combining the data for isovector and isoscalar contributions, if the kinematical consequences of the isospin violation due to different masses for charged and neutral pions are taken into account.
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| 10. |
- Adlarson, Patrik, et al.
(författare)
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Measurement of the pn -> pp pi(0)pi(-) reaction in search for the recently observed resonance structure in d pi(0)pi(0) and d pi(+)pi(-) systems
- 2013
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 88:5, s. 055208-
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Tidskriftsartikel (refereegranskat)abstract
- Exclusive measurements of the quasifree pn -> pp pi(0)pi(-) reaction have been performed by means of pd collisions at T-p = 1.2 GeV using the wide angle shower apparatus (WASA) detector setup at the cooler synchrotron COSY (Institut fur Kernphysik, Julich). Total and differential cross sections have been obtained covering the energy region root s = (2.35-2.46) GeV, which includes the region of the ABC effect and its associated resonance structure. NoABCeffect, i.e., low-mass enhancement is found in the pi(0)pi(-) -invariant mass spectrum, in agreement with the constraint from Bose statistics that the isovector pion pair can not be in relative s wave. At the upper end of the covered energy region t-channel processes for Roper, Delta(1600) and Delta Delta excitations provide a reasonable description of the data, but at low energies the measured cross sections are much larger than predicted by such processes. Adding a resonance amplitude for the resonance at m = 2.37 GeV with Gamma = 70 MeV and I (J(P)) = 0(3(+)) observed recently in pn -> d pi(0)pi(0) and pn -> d pi(+)pi(-) reactions leads to an agreement with the data also at low energies.
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