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- Abe, O, et al.
(author)
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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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In: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Journal article (peer-reviewed)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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- Toshito, T., et al.
(author)
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Measurements of projectile-like Be-8 and B-9 production in 200-400 MeV/nucleon C-12 on water
- 2008
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In: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 78:6, s. 4-
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Journal article (peer-reviewed)abstract
- We have studied the production of the projectile-like fragments Be-8 and B-9 produced in interactions of 200 to 400 MeV/nucleon carbon ions with water, using emulsion detectors. In this Brief Report we present the first published production cross section of the projectile-like fragment B-9 in the energy region above 100 MeV/nucleon. The measured production cross sections of these nuclides were compared to calculations using a semiempirical model. We found that the measured cross sections deviate from the calculated values by a factor up to about six. This information is of importance for benchmarking and improving heavy ion nuclear reaction models.
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- Toshito, T., et al.
(author)
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Measurements of total and partial charge-changing cross sections for 200-to 400-MeV/nucleon C-12 on water and polycarbonate
- 2007
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In: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 75:5, s. 8-
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Journal article (peer-reviewed)abstract
- We have studied charged nuclear fragments produced by 200- to 400-MeV/nucleon carbon ions, interacting with water and polycarbonate, using a newly developed emulsion detector. Total and partial charge-changing cross sections for the production of B, Be, and Li fragments were measured and compared with both previously published measurements and model predictions. This study is of importance for validating and improving carbon-ion therapy treatment planning systems and for estimating the radiological risks for personnel on space missions, because carbon is a significant component of galactic cosmic rays.
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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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In: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Research review (peer-reviewed)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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- Lunde, J., et al.
(author)
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Ion-dispersion and rapid electron fluctuations in the cusp : a case study
- 2008
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In: Annales Geophysicae. - 0992-7689 .- 1432-0576. ; 26:8, s. 2485-2502
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Journal article (peer-reviewed)abstract
- We present results from co-ordinated measurements with the low altitude REIMEI satellite and the ESR (EISCAT Svalbard Radar), together with other ground-based instruments carried out in February 2006. The results mainly relate to the dayside cusp where clear signatures of so-called ion-dispersion are seen in the satellite data. The cusp ion-dispersion is important for helping to understand the temporal and spatial structure of magnetopause reconnection. Whenever a satellite crosses boundaries of flux tubes or convection cells, cusp structures such as ion-dispersion will always be encountered. In our case we observed 3 distinct steps in the ion energy, but it includes at least 2 more steps as well, which we interpret as temporal features in relation to pulsed reconnection at the magnetopause. In addition, fast variations of the electron flux and energy occurring during these events have been studied in detail. The variations of the electron population, if interpreted as structures crossed by the REIMEI satellite, would map near the magnetopause to similar features as observed previously with the Cluster satellites. These were explained as Alfven waves originating from an X-line of magnetic reconnection.
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- Ogawa, Y., et al.
(author)
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Coordinated EISCAT Svalbard radar and Reimei satellite observations of ion upflows and suprathermal ions
- 2008
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In: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 113:A5, s. A05306-
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Journal article (peer-reviewed)abstract
- The relationship between bulk ion upflows and suprathermal ions was investigated using data simultaneously obtained from the European Incoherent Scatter (EISCAT) Svalbard radar (ESR) and the Reimei satellite. Simultaneous observations were conducted in November 2005 and August 2006, and 14 conjunction data sets have been obtained at approximately 630 km in the dayside ionosphere. Suprathermal ions with energies of a few eV were present in the dayside cusp region, and the ion velocity distribution changed from an isotropic Maxwellian near the cusp region to tail heating at energies above a few eV in the cusp region. The velocity distribution of the suprathermal ions has a peak perpendicular or oblique to the geomagnetic field, and the temperature of the suprathermal ions was 0.9-1.4 eV. An increase in the phase space density (PSD) of the suprathermal ions, measured with the Reimei, was correlated with bulk ion upflow observed at the same altitude using EISCAT, and with the energy flux of precipitating electrons with energies of 50-500 eV. The PSD also has a good correlation with the electron temperature, which was increased by precipitation, but not with the ion temperature (0.1-0.3 eV) at the same altitude measured with EISCAT. These results suggest that plasma waves such as broadband extremely low frequency (BBELF) wavefields associated with precipitation are connected to the bulk ion upflows in the cusp and effectively cause the heating of suprathermal ions. The heating of suprathermal ions disagrees with anisotropic heating due to O+-O resonant charge exchange.
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