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- 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. |
- Michelsen, H. A., et al.
(författare)
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Modeling laser-induced incandescence of soot: a summary and comparison of LII models
- 2007
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Ingår i: Applied Physics B. - : Springer Science and Business Media LLC. - 0946-2171 .- 1432-0649. ; 87:3, s. 503-521
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Tidskriftsartikel (refereegranskat)abstract
- We have performed a comparison of ten models that predict the temporal behavior of laser-induced incandescence (LII) of soot. In this paper we present a summary of the models and comparisons of calculated temperatures, diameters, signals, and energy-balance terms. The models were run assuming laser heating at 532 nm at fluences of 0.05 and 0.70 J/cm(2) with a laser temporal profile provided. Calculations were performed for a single primary particle with a diameter of 30 nm at an ambient temperature of 1800 K and a pressure of 1 bar. Preliminary calculations were performed with a fully constrained model. The comparison of unconstrained models demonstrates a wide spread in calculated LII signals. Many of the differences can be attributed to the values of a few important parameters, such as the refractive-index function E(m) and thermal and mass accommodation coefficients. Constraining these parameters brings most of the models into much better agreement with each other, particularly for the low-fluence case. Agreement among models is not as good for the high-fluence case, even when selected parameters are constrained. The reason for greater variability in model results at high fluence appears to be related to solution approaches to mass and heat loss by sublimation.
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- Zeggini, Eleftheria, et al.
(författare)
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Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 638-645
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
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- Al-Khatib, A, et al.
(författare)
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Transition to non-collective states at high spin in Xe-124
- 2008
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 36:1, s. 21-29
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in Xe-124 were populated in the reaction Se-82(Ca-48, 6n) Xe-124 and gamma-ray coincidence relationships were measured with the Gammasphere spectrometer. Two new bands are observed and several of the previously known bands are extended in the high-as well as in the low-spin region. Two irregular high-spin structures are also added. The irregularities are a fingerprint of a transition from collective to non-collective behaviour. Configuration assignments to the new structures are proposed on the basis of systematics and by comparing experimental properties with calculations within the framework of the cranking model.
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- Chauhan, B C, et al.
(författare)
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Practical Recommendations for Measuring Rates of Visual Field Change in Glaucoma
- 2008
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Ingår i: British Journal of Ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 92, s. 569-573
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Tidskriftsartikel (refereegranskat)abstract
- Statement of Interest Assessment of visual field damage is the major index of the functional impact of glaucoma with direct relevance to quality of life measures. Visual field change was used as a primary endpoint for progression in the recent glaucoma trials and its measurement is the cornerstone of glaucoma management influencing therapeutic decisions. The objective of this perspective is to provide practical recommendations for measuring clinically relevant rates of glaucomatous visual field progression to help identify patients at risk for visual impairment. They focus on the frequency of examinations required for detecting various amounts and rates of visual field change.
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| 8. |
- Davies, R.J., et al.
(författare)
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A user driven approach to develop a cognitive prosthetic to address the unmet needs of people with mild dementia
- 2009
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Ingår i: Pervasive and Mobile Computing. - : Elsevier BV. - 1574-1192 .- 1873-1589. ; 5:3, s. 253-267
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Tidskriftsartikel (refereegranskat)abstract
- This paper aims to provide the details of the approach adopted in the development of a cognitive prosthetic aimed to help address the unmet needs of people with mild dementia. The approach adopted is based on a waterfall style approach consisting of a series of three phases each of which contributes to the progression and improvement of a cognitive prosthetic-based solution. Within each phase, distinct stages of design, development and evaluation of the cognitive solution are conducted. The current paper discusses the distinct stages conducted in the first phase of the project which resulted in the design and development of a user driven solution based on the needs of 17 patient/carer dyads across three trial sites.
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| 10. |
- Hom, Geoffrey, et al.
(författare)
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Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX.
- 2008
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 358:9, s. 900-909
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease in which the risk of disease is influenced by complex genetic and environmental contributions. Alleles of HLA-DRB1, IRF5, and STAT4are established susceptibility genes; there is strong evidence for the existence of additional risk loci.METHODS: We genotyped more than 500,000 single-nucleotide polymorphisms (SNPs) in DNA samples from 1311 case subjects with SLE and 1783 control subjects; all subjects were North Americans of European descent. Genotypes from 1557 additional control subjects were obtained from public data repositories. We measured the association between the SNPs and SLE after applying strict quality-control filters to reduce technical artifacts and to correct for the presence of population stratification. Replication of the top loci was performed in 793 case subjects and 857 control subjects from Sweden.RESULTS: Genetic variation in the region upstream from the transcription initiation site of the gene encoding B lymphoid tyrosine kinase (BLK) and C8orf13 (chromosome 8p23.1) was associated with disease risk in both the U.S. and Swedish case–control series (rs13277113; odds ratio, 1.39; P=1×10−10) and also with altered levels of messenger RNA in B-cell lines. In addition, variants on chromosome 16p11.22, near the genes encoding integrin alpha M (ITGAM, or CD11b) and integrin alpha X (ITGAX), were associated with SLE in the combined sample (rs11574637; odds ratio, 1.33; P=3×10−11).
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