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| 2. |
- Grover, A, et al.
(författare)
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A novel tau mutation in exon 9 (1260V) causes a four-repeat tauopathy
- 2003
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Ingår i: Experimental Neurology. - 0014-4886. ; 184:1, s. 131-140
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Tidskriftsartikel (refereegranskat)abstract
- A novel mutation in exon 9 of tau, I260V, is associated with a clinical syndrome consistent with frontotemporal dementia with extensive tau pathology; however, neurofibrillary tangles and Pick bodies are absent. Significantly, Sarkosyl- insoluble tau extracted from affected brain tissue consisted almost exclusively of four-repeat isoforms. Consistent with these findings, in vitro biochemical assays demonstrated that the I260V mutation causes a selective increase in tau aggregation and a decrease in tau-induced microtubule assembly with four-repeat isoforms only. The contrasting pathology and biochemical effects of this mutation suggest a different disease mechanism from the other exon 9 mutations and demonstrates the critical role for the first microtubule-binding domain in tau-promoted microtubule assembly and the pathogenic aggregation of tau.
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| 3. |
- Tabar, L., et al.
(författare)
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Number needed to screen : Lives saved over 20 years of follow-up in mammographic screening
- 2004
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Ingår i: Journal of Medical Screening. - : SAGE Publications. - 0969-1413 .- 1475-5793. ; 11:3, s. 126-129
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To estimate the number needed to screen with mammography to save one life, based on a stated amount of screening activity and long-term follow-up for breast cancer death. Setting: A randomised controlled trial of mammographic screening for breast cancer, with 77,080 women invited to screening and 55,985 not invited. The invited group was offered screening for seven years. Follow-up continued for a total of just over 20 years. Methods: Number needed to screen for seven years to save one life over 20 years was calculated by dividing the number screened (not the number invited) by the total number of lives saved. Similarly, we calculated the number of mammographic examinations required to save one life. Results: We estimate that the number of women needed to screen for seven years to save one life over 20 years is 465 (95% CI 324-819). The number of mammographic examinations needed to save one life was 1499 (95% CI 1046-2642). Conclusions: The number needed to screen to save one life is smaller than has been reported in the past. Mammographic screening is effective in absolute terms as well as relative. Long-term follow-up allowed us to estimate the absolute benefit with greater accuracy.
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| 4. |
- Duffy, S.W., et al.
(författare)
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The Swedish two-county trial of mammographic screening : Cluster randomisation and end point evaluation
- 2003
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 14:8, s. 1196-1198
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Swedish Two-County Trial has been criticised on the grounds of the cluster randomisation and alleged bias in classification of cause of death. Patients and methods: In the Two-County Trial, 77080 women were randomised to regular invitation to screening (active study population, ASP) and 55985 to no invitation (passive study population, PSP), in 45 geographical clusters. After ~7 years, the PSP was invited to screening and the trial closed. We analysed data using hierarchical statistical models to take account of cluster randomisation, and performed a conservative analysis assuming a systematic difference between ASP and PSP in baseline breast cancer mortality in one of the counties. We also analysed deaths from causes other than breast cancer and from all causes among breast cancer cases diagnosed in the ASP and PSP. Results: Taking account of the cluster randomisation there was a significant 30% reduction in breast cancer mortality in the ASP. Conservatively, assuming a systematic difference between ASP and PSP clusters in baseline breast cancer mortality, there was a significant 27% reduction in mortality in the ASP. Ignoring classification of cause of death, there was a significant 13% reduction in all-cause mortality in breast cancer cases in the ASP. Conclusions: Breast cancer mortality is a valid end point and mammographic screening does indeed reduce mortality from breast cancer. The criticisms of the Swedish Two-County Trial are unfounded.
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| 5. |
- Tabar, L., et al.
(författare)
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All-cause mortality among breast cancer patients in a screening trial : Support for breast cancer mortality as an end point
- 2002
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Ingår i: Journal of Medical Screening. - : SAGE Publications. - 0969-1413 .- 1475-5793. ; 9:4, s. 159-162
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has recently been suggested that all-cause mortality is a more appropriate end point than disease specific mortality in cancer screening trials, and that disease specific mortality is biased in favour of screening. This suggestion is based partly on supposed inconsistencies between all-cause mortality results and disease specific results in cancer screening trials, and alleged increases in deaths from causes other than breast cancer among breast cancer cases diagnosed among women invited to screening. Methods: We used data from the Swedish Two-County Trial of mammographic screening for breast cancer, in which 77 080 women were randomised to an invitation to screening and 55 985 to no invitation. We estimated relative risks (RRs) (invited v control) of death from breast cancer, death from other causes within the breast cancer cases, and death from all causes within the breast cancer cases. RRs were adjusted for age and took account of the longer follow up of breast cancer cases in the invited group due to lead time. Results: There was a significant 31% reduction in breast cancer mortality in the invited group (RR 0.69, 95% confidence interval (Cl) 0.58-0.80, p
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