| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- 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.
|
|
| 5. |
- Power, M. J., et al.
(författare)
-
Changes in fire regimes since the Last Glacial Maximum : an assessment based on a global synthesis and analysis of charcoal data
- 2008
-
Ingår i: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894. ; 30:7-8, s. 887-907
-
Tidskriftsartikel (refereegranskat)abstract
- Fire activity has varied globally and continuously since the last glacial maximum (LGM) in response to long-term changes in global climate and shorter-term regional changes in climate, vegetation, and human land use. We have synthesized sedimentary charcoal records of biomass burning since the LGM and present global maps showing changes in fire activity for time slices during the past 21,000 years (as differences in charcoal accumulation values compared to pre-industrial). There is strong broad-scale coherence in fire activity after the LGM, but spatial heterogeneity in the signals increases thereafter. In North America, Europe and southern South America, charcoal records indicate less-than-present fire activity during the deglacial period, from 21,000 to ∼11,000 cal yr BP. In contrast, the tropical latitudes of South America and Africa show greater-than-present fire activity from ∼19,000 to ∼17,000 cal yr BP and most sites from Indochina and Australia show greater-than-present fire activity from 16,000 to ∼13,000 cal yr BP. Many sites indicate greater-than-present or near-present activity during the Holocene with the exception of eastern North America and eastern Asia from 8,000 to ∼3,000 cal yr BP, Indonesia and Australia from 11,000 to 4,000 cal yr BP, and southern South America from 6,000 to 3,000 cal yr BP where fire activity was less than present. Regional coherence in the patterns of change in fire activity was evident throughout the post-glacial period. These complex patterns can largely be explained in terms of large-scale climate controls modulated by local changes in vegetation and fuel load.
|
|
| 6. |
- Pierce, D. M., et al.
(författare)
-
A computational framework for patient-specific analysis of articular cartilage incorporating structural information from DT-MRI
- 2009
-
Ingår i: GAMM Mitteilungen. - : Wiley. - 0936-7195 .- 1522-2608. ; 32:2, s. 157-177
-
Tidskriftsartikel (refereegranskat)abstract
- Accurate techniques for simulating soft biological tissue deformation are an increasingly valuable tool in many areas of biomechanical analysis and medical image computing. To model the morphology and the material response of human articular cartilage a phenomenological and patient-specific simulation approach incorporating the collagen fibre fabric is proposed. We then demonstrate a unique combination of ultra-high field Diffusion Tensor Magnetic Resonance Imaging (17.6T DT-MRI) and a novel numerical approach incorporating the empirical data to predict the collagen fibre fabric deformation for an indentation experiment.
|
|
| 7. |
- Pierce, D. M., et al.
(författare)
-
A Phenomenological Approach Toward Patient-Specific Computational Modeling of Articular Cartilage Including Collagen Fiber Tracking
- 2009
-
Ingår i: Journal of Biomechanical Engineering. - : ASME International. - 0148-0731 .- 1528-8951. ; 131:9
-
Tidskriftsartikel (refereegranskat)abstract
- To model the cartilage morphology and the material response, a phenomenological and patient-specific simulation approach incorporating the collagen fiber fabric is proposed. Cartilage tissue response is nearly isochoric and time-dependent under physiological pressure levels. Hence, a viscoelastic constitutive model capable of reproducing finite strains is employed, while the time-dependent deformation change is purely isochoric. The model incorporates seven material parameters, which all have a physical interpretation. To calibrate the model and facilitate further analysis, five human cartilage specmiens underwent a number of tests. A series of magnetic resonance imaging (MRI) sequences is taken, next the cartilage surface is imaged, then mechanical indentation tests arc completed at 2-7 different locations per sample, resulting in force/displacement data over time, and finally, the underlying bone surface is imaged. Imaging and mechanical testing are performed with a custom-built robotics-based testing device. Stereo reconstruction of the cartilage and subchondral bone surface is employed, which, together with the proposed constitutive model, led to specimen-specific finite element simulations of the mechanical indentation tests. The force-time response of 23 such indentation experiment simulations is optimized to estimate the mean material parameters and corresponding standard deviations. The model is capable of reproducing the deformation behavior of human articular cartilage in the physiological loading domain, as demonstrated by the good agreement between the experiment and numerical results (R-2 = 0.95 +/- 0.03, mean +/- standard deviation of force-time response for 23 indentation tests). To address validation, a sevenfold cross-validation experiment is performed on the 21 experiments representing health), cartilage. To quantify the predictive error, the mean of the absolute force differences and Pearson's correlation coefficient are both calculated. Deviations in the mean absolute difference, normalized by the peak force, range from 4% to 90%, with 40 +/- 25% (M +/- SD). The correlation coefficients across all predictions have a minimum of 0.939, and a maximum of 0.993 with 0.975 +/- 0.013 (M +/- SD), which demonstrates an excellent match of the decay characteristics. A novel feature of the proposed method is 3D sample-specific numerical tracking of the fiber fabric deformation under general loading. This feature is demonstrated by comparing the estimated fiber fabric deformation with recently published experimental data determined by diffusion tensor MRI. The proposed approach is efficient enough to enable large-scale 3D contact simulations of knee joint loading in simulations with accurate joint geometries. [DOI: 10.1115/1.3148471]
|
|
| 8. |
|
|
