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| 2. |
- 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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| 4. |
- Ng, M Y M, et al.
(författare)
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Meta-analysis of 32 genome-wide linkage studies of schizophrenia
- 2009
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 14:8, s. 774-785
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Tidskriftsartikel (refereegranskat)abstract
- A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P(SR)) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies.
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| 6. |
- Riley, M A, et al.
(författare)
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Beyond band termination in Er-157 and the search for wobbling excitations in strongly deformed Hf-174
- 2005
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 31:10, s. 1735-1740
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Tidskriftsartikel (refereegranskat)abstract
- High-spin terminating bands in heavy nuclei were first identified in nuclei around Er-158(90). While examples of special terminating states have been identified in a number of erbium isotopes, almost nothing is known about the states lying beyond band termination. In the present work the high-spin structure of Er-157 has been studied using the Gammasphere spectrometer. The subject of triaxial superdeformation and 'wobbling' modes in Lu nuclei has rightly attracted a great deal of attention. Very recently, four strongly or superdeformed (SD) sequences have been observed in Hf-174 and ultimate cranker calculations predict, such structures may have significant triaxial deformation. We have performed two experiments in an attempt to verify the possible triaxial nature of these bands. A lifetime measurement was performed to confirm the large (and similar) deformation of the bands. In addition, a high-statistics, thin-target experiment was run to search for linking transitions between the SD bands and possible wobbling modes.
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| 7. |
- Riley, M. A., et al.
(författare)
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Observation of states beyond band termination in Er-156,Er-157,Er-158 and strongly deformed structures in Hf-173,Hf-174,Hf-175
- 2006
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Ingår i: Physica Scripta. - 0031-8949. ; T125, s. 123-126
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Tidskriftsartikel (refereegranskat)abstract
- High-spin terminating bands in heavy nuclei were first identified in nuclei around Er-158(90). While examples of terminating states have been identified in a number of erbium isotopes, almost nothing is known about the states lying beyond band termination. In the present work, the high-spin structure of Er-156,Er-157,Er-158 has been studied using the Gammasphere spectrometer. The subject of triaxial superdeformation and 'wobbling' modes in Lu nuclei has rightly attracted a great deal of attention. Very recently four strongly or superdeformed (SD) sequences have been observed in Hf-174, and cranking calculations using the Ultimate Cranker code predict that such structures may have significant triaxial deformation. We have performed two experiments in an attempt to verify the possible triaxial nature of these bands. A lifetime measurement was performed to confirm the large (and similar) deformation of the bands. In addition, a high-statistics, thin-target experiment took place to search for linking transitions between the SD bands, possible wobbling modes, and new SD band structures.
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| 8. |
- Riley, M. A., et al.
(författare)
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Strongly Deformed Nuclear Shapes at Ultra-High Spin and Shape Coexistence in N\sim 90 Nuclei
- 2009
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Ingår i: Acta Physica Polonica B. - 0587-4254. ; 40:3, s. 513-522
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Tidskriftsartikel (refereegranskat)abstract
- The N similar to 90 region of the nuclear chart has featured prominently as the spectroscopy of nuclei at extreme spin has progressed. This talk will present recent discoveries from investigations of high spin behavior in the N similar to 90 Er, Tm and Yb nuclei utilizing the Gammasphere gamma-ray spectrometer. In particular it will include discussion of the beautiful shape evolution and coexistence observed in these nuclei along with the identification of a remarkable new family of band structures. The latter are very weakly populated rotational sequences with high moment of inertia that bypass the classic terminating configurations near spin 40-50 (h) over bar, marking a return to collectivity that extends discrete gamma-ray spectroscopy to well over 60 (h) over bar. Establishing the nature of the yrast states in these nuclei beyond the oblate band-termination states has been a major goal for the past two decades. Cranking calculations suggest that these new structures most likely represent stable triaxial strongly deformed bands that lie in a valley of favored shell energy in deformation and particle-number space.
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| 9. |
- Nelson, A. J., et al.
(författare)
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Soft x-ray free electron laser microfocus for exploring matter under extreme conditions
- 2009
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Ingår i: Optics Express. - 1094-4087. ; 17:20, s. 18271-18278
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Tidskriftsartikel (refereegranskat)abstract
- We have focused a beam (BL3) of FLASH (Free-electron LASer in Hamburg: lambda = 13.5 nm, pulse length 15 fs, pulse energy 10-40 mu J, 5Hz) using a fine polished off-axis parabola having a focal length of 270 mm and coated with a Mo/Si multilayer with an initial reflectivity of 67% at 13.5 nm. The OAP was mounted and aligned with a picomotor controlled six-axis gimbal. Beam imprints on poly(methyl methacrylate) -PMMA were used to measure focus and the focused beam was used to create isochoric heating of various slab targets. Results show the focal spot has a diameter of <= 1 mu m. Observations were correlated with simulations of best focus to provide further relevant information.
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| 10. |
- Osoegawa, K., et al.
(författare)
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Identification of novel candidate genes associated with cleft lip and palate using array comparative genomic hybridisation
- 2008
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 45:2, s. 81-86
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Tidskriftsartikel (refereegranskat)abstract
- Aim and method: We analysed DNA samples isolated from individuals born with cleft lip and cleft palate to identify deletions and duplications of candidate gene loci using array comparative genomic hybridisation (array-CGH). Results: Of 83 syndromic cases analysed we identified one subject with a previously unknown 2.7 Mb deletion at 22q11.21 coinciding with the DiGeorge syndrome region. Eighteen of the syndromic cases had clinical features of Van der Woude syndrome and deletions were identified in five of these, all of which encompassed the interferon regulatory factor 6 (IRF6) gene. In a series of 104 non-syndromic cases we found one subject with a 3.2 Mb deletion at chromosome 6q25.1-25.2 and another with a 2.2 Mb deletion at 10q26.11-26.13. Analyses of parental DNA demonstrated that the two deletion cases at 22q11.21 and 6q25.1-25.2 were de novo, while the deletion of 10q26.11-26.13 was inherited from the mother, who also has a cleft lip. These deletions appear likely to be causally associated with the phenotypes of the subjects. Estrogen receptor 1 (ESR1) and fibroblast growth factor receptor 2 (FGFR2) genes from the 6q25.1-25.2 and 10q26.11-26.13, respectively, were identified as likely causative genes using a gene prioritisation software. Conclusion: We have shown that array-CGH analysis of DNA samples derived from cleft lip and palate subjects is an efficient and productive method for identifying candidate chromosomal loci and genes, complementing traditional genetic mapping strategies.
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