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Sökning: WFRF:(Toft U)

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  • Abe, O, et al. (författare)
  • Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
  • 2005
  • Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
  • 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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  • Taddei, C, et al. (författare)
  • Repositioning of the global epicentre of non-optimal cholesterol
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
  • Tidskriftsartikel (refereegranskat)abstract
    • High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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  • Quist-Paulsen, P., et al. (författare)
  • T-cell acute lymphoblastic leukemia in patients 1-45 years treated with the pediatric NOPHO ALL2008 protocol
  • 2020
  • Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 34:2, s. 347-357
  • Tidskriftsartikel (refereegranskat)abstract
    • The NOPHO ALL2008 is a population-based study using an unmodified pediatric protocol in patients 1-45 years of age with acute lymphoblastic leukemia. Patients with T-ALL were given a traditional pediatric scheme if fast responding (minimal residual disease (MRD) < 0.1% day 29), or intensive block-based chemotherapy if slow responding (MRD > 0.1% day 29). Both treatment arms included pediatric doses of high-dose methotrexate and asparaginase. If MRD >= 5% on day 29 or >= 0.1% after consolidation, patients were assigned to allogeneic hematopoietic stem cell transplantation. The 5-year overall survival of the 278 T-ALL patients was 0.75 (95% CI 0.69-0.81), being 0.82 (0.74-0.88) for patients 1.0-9.9 years, 0.76 (0.66-0.86) for those 10.0-17.9 years, and 0.65 (0.55-0.75) for the older patients. The risk of death in first remission was significantly higher in adults (12%) compared with the 1-9 years group (4%). The MRD responses in the three age groups were similar, and only a nonsignificant increase in relapse risk was found in adults. In conclusion, an unmodified pediatric protocol in patients 1-45 years is effective in all age groups. The traditional pediatric treatment schedule was safe for all patients, but the intensive block therapy led to a high toxic death rate in adults.
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  • Ekström, Andreas, et al. (författare)
  • Electric quadrupole moments of the 2(1)(+) states in Cd-100,Cd-102,Cd-104
  • 2009
  • Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 80:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Using the REX-ISOLDE facility at CERN the Coulomb excitation cross sections for the 0(gs)(+)-> 2(1)(+) transition in the beta-unstable isotopes Cd-100,Cd-102,Cd-104 have been measured for the first time. Two different targets were used, which allows for the first extraction of the static electric quadrupole moments Q(2(1)(+)) in Cd-102,Cd-104. In addition to the B(E2) values in Cd-102,Cd-104, a first experimental limit for the B(E2) value in Cd-100 is presented. The data was analyzed using the maximum likelihood method. The provided probability distributions impose a test for theoretical predictions of the static and dynamic moments. The data are interpreted within the shell-model using realistic matrix elements obtained from a G-matrix renormalized CD-Bonn interaction. In view of recent results for the light Sn isotopes the data are discussed in the context of a renormalization of the neutron effective charge. This study is the first to use the reorientation effect for post-accelerated short-lived radioactive isotopes to simultaneously determine the B(E2) and the Q(2(1)(+)) values.
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  • Fynbo, J. P. U., et al. (författare)
  • Galaxy counterparts of metal-rich damped Ly alpha absorbers - I. The case of the z=2.35 DLA towards Q2222-0946
  • 2010
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 408:4, s. 2128-2136
  • Tidskriftsartikel (refereegranskat)abstract
    • We have initiated a survey using the newly commissioned X-shooter spectrograph to target candidate relatively metal-rich damped Ly alpha absorbers (DLAs). Our rationale is that high-metallicity DLAs due to the luminosity-metallicity relation likely will have the most luminous galaxy counterparts. In addition, the spectral coverage of X-shooter allows us to search for not only Ly alpha emission, but also rest-frame optical emission lines. We have chosen DLAs where the strongest rest-frame optical lines ([O II], [O III], H beta and H alpha) fall in the near-infrared atmospheric transmission bands. In this first paper resulting from the survey, we report on the discovery of the galaxy counterpart of the z(abs) = 2.354 DLA towards the z = 2.926 quasar Q2222-0946. This DLA is amongst the most metal-rich z > 2 DLAs studied so far at comparable redshifts and there is evidence for substantial depletion of refractory elements on to dust grains. We measure metallicities from Zn II, Si II, Ni II, Mn II and Fe II of -0.46 +/- 0.07, -0.51 +/- 0.06, -0.85 +/- 0.06, -1.23 +/- 0.06 and -0.99 +/- 0.06, respectively. The galaxy is detected in the Ly alpha, [O III] lambda lambda 4959, 5007 and H alpha emission lines at an impact parameter of about 0.8 arcsec (6 kpc at z(abs) = 2.354). Based on the H alpha line, we infer a star formation rate of 10M(circle dot) yr(-1), which is a lower limit due to the possibility of slit loss. Compared to the recently determined H alpha luminosity function for z = 2.2 galaxies, the DLA-galaxy counterpart has a luminosity of L similar to 0.1L*(H alpha). The emission-line ratios are 4.0 (Ly alpha/H alpha) and 1.2 ([O III]/H alpha). In particular, the Ly alpha line shows clear evidence for resonant scattering effects, namely an asymmetric, redshifted (relative to the systemic redshift) component and a much weaker blueshifted component. The fact that the blueshifted component is relatively weak indicates the presence of a galactic wind. The properties of the galaxy counterpart of this DLA are consistent with the prediction that metal-rich DLAs are associated with the most luminous of the DLA-galaxy counterparts.
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  • Fynbo, J. P. U., et al. (författare)
  • Galaxy counterparts of metal-rich damped Ly alpha absorbers - II. A solar-metallicity and dusty DLA at z(abs)=2.58
  • 2011
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 413:4, s. 2481-2488
  • Tidskriftsartikel (refereegranskat)abstract
    • This is the second paper of a series reporting on the results from a survey conducted with the ESO VLT/X-shooter spectrograph. We target high-metallicity damped Lyman alpha absorbers (DLAs) with the aim of investigating the relation between galaxies detected in emission and those detected in absorption. Here, we report on the discovery of the galaxy counterpart of the z(abs) = 2.58 DLA on the line-of-sight to the z = 3.07 quasar SDSS J 091826.16+163609.0 (hereafter Q 0918+1636). The galaxy counterpart of the DLA is detected in the [O iii] lambda 5007 and [O ii] lambda lambda 3726, 3729 emission lines redshifted into the NIR at an impact parameter of 2.0 arcsec (16 kpc at z = 2.58). Ly alpha emission is not detected down to a 3 Sigma detection limit of 5 x 10-18 erg s-1 cm-2, which, compared to the strength of the oxygen lines, implies that Ly alpha emission from this galaxy is suppressed by more than an order of magnitude. The DLA has one of the highest metallicities measured so far at comparable redshifts. We find evidence for substantial depletion of refractory elements on to dust grains. Fitting the main metal line component of the DLA, which is located at z(abs) = 2.5832, we measure the metal abundances from Zn ii, S ii, Si ii, Cr ii, Mn ii, Fe ii and Ni ii to be -0.12 +/- 0.05, -0.26 +/- 0.05, -0.46 +/- 0.05, -0.88 +/- 0.05, -0.92 +/- 0.05, -1.03 +/- 0.05 and -0.78 +/- 0.05, respectively. In addition, we detect absorption in the Lyman and Werner bands of molecular hydrogen (H(2)), which represents the first detection of H(2) molecules with X-shooter. The background quasar Q 0918+1636 is amongst the reddest QSOs at redshifts 3.02 < z < 3.12 from the SDSS catalogue. Its UV to NIR spectrum is well fitted by a composite QSO spectrum reddened by SMC-/LMC-like extinction curves at z(abs) = 2.58 with a significant amount of extinction given by A(V) approximate to 0.2 mag. This supports previous claims that there may be more metal-rich DLAs missing from current samples due to dust reddening of the background QSOs. The fact that there is evidence for dust both in the central emitting regions of the galaxy (as evidenced by the lack of Ly alpha emission) and at an impact parameter of 16 kpc (as probed by the DLA) suggests that dust is widespread in this system.
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