285 research outputs found

    Overdiagnosis and overtreatment of breast cancer: Overdiagnosis in randomised controlled trials of breast cancer screening

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    Data from randomised controlled trials of mammographic screening can be used to determine the extent of any overdiagnosis, as soon as either a time equivalent to the lead-time has elapsed after the final screen, or the control arm has been offered screening. This paper reviews those randomised trials for which breast cancer incidence data are available. In recent trials in which the control group has not been offered screening, an excess incidence of breast cancer remains after many years of follow-up. In those trials in which the control arm has been offered screening, although there is a possible shift from invasive to in situ disease, there is no evidence of overdiagnosis as a result of incident screens

    Meta-analysis of breast cancer mortality benefit and overdiagnosis adjusted for adherence: improving information on the effects of attending screening mammography

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    Background: Women require information about the impact of regularly attending screening mammography on breast cancer mortality and overdiagnosis to make informed decisions. To provide this information we aimed to meta-analyse randomised controlled trials adjusted for adherence to the trial protocol. Methods: Nine screening mammography trials used in the Independent UK Breast Screening Report were selected. Extending an existing approach to adjust intention-to-treat (ITT) estimates for less than 100% adherence rates, we conducted a random-effects meta-analysis. This produced a combined deattenuated prevented fraction and a combined deattenuated percentage risk of overdiagnosis. Results: In women aged 39–75 years invited to screen, the prevented fraction of breast cancer mortality at 13-year follow-up was 0.22 (95% CI 0.15–0.28) and it increased to 0.30 (95% CI 0.18–0.42) with deattenuation. In women aged 40–69 years invited to screen, the ITT percentage risk of overdiagnosis during the screening period was 19.0% (95% CI 15.2–22.7%), deattenuation increased this to 29.7% (95% CI 17.8–41.5%). Conclusions: Adjustment for nonadherence increased the size of the mortality benefit and risk of overdiagnosis by up to 50%. These estimates are more appropriate when developing quantitative information to support individual decisions about attending screening mammography

    Condensed Mitotic Chromosome Structure at Nanometer Resolution Using PALM and EGFP- Histones

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    Photoactivated localization microscopy (PALM) and related fluorescent biological imaging methods are capable of providing very high spatial resolutions (up to 20 nm). Two major demands limit its widespread use on biological samples: requirements for photoactivatable/photoconvertible fluorescent molecules, which are sometimes difficult to incorporate, and high background signals from autofluorescence or fluorophores in adjacent focal planes in three-dimensional imaging which reduces PALM resolution significantly. We present here a high-resolution PALM method utilizing conventional EGFP as the photoconvertible fluorophore, improved algorithms to deal with high levels of biological background noise, and apply this to imaging higher order chromatin structure. We found that the emission wavelength of EGFP is efficiently converted from green to red when exposed to blue light in the presence of reduced riboflavin. The photon yield of red-converted EGFP using riboflavin is comparable to other bright photoconvertible fluorescent proteins that allow <20 nm resolution. We further found that image pre-processing using a combination of denoising and deconvolution of the raw PALM images substantially improved the spatial resolution of the reconstruction from noisy images. Performing PALM on Drosophila mitotic chromosomes labeled with H2AvD-EGFP, a histone H2A variant, revealed filamentous components of ∼70 nm. This is the first observation of fine chromatin filaments specific for one histone variant at a resolution approximating that of conventional electron microscope images (10–30 nm). As demonstrated by modeling and experiments on a challenging specimen, the techniques described here facilitate super-resolution fluorescent imaging with common biological samples

    “It’s for us –newcomers, LGBTQ persons, and HIV-positive persons. You feel free to be”: a qualitative study exploring social support group participation among African and Caribbean lesbian, gay, bisexual and transgender newcomers and refugees in Toronto, Canada

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    BACKGROUND: Stigma and discrimination harm the wellbeing of lesbian, gay, bisexual and transgender (LGBT) people and contribute to migration from contexts of sexual persecution and criminalization. Yet LGBT newcomers and refugees often face marginalization and struggles meeting the social determinants of health (SDOH) following immigration to countries such as Canada. Social isolation is a key social determinant of health that may play a significant role in shaping health disparities among LGBT newcomers and refugees. Social support may moderate the effect of stressors on mental health, reduce social isolation, and build social networks. Scant research, however, has examined social support groups targeting LGBT newcomers and refugees. The purpose of this qualitative study was to explore experiences of social support group participation among LGBT African and Caribbean newcomers and refugees in an urban Canadian city. METHODS: We conducted 3 focus groups with a venue-based sample of LGBT African and Caribbean newcomers and refugees (n = 29) who attended social support groups at an ethno-specific AIDS Service Organization. Focus groups followed a semi-structured interview guide and were analyzed using narrative thematic techniques. RESULTS: Participant narratives highlighted immigration stressors, social isolation, mental health issues, and challenges meeting the SDOH. Findings reveal multi-level benefits of social support group participation at intrapersonal (self-acceptance, improved mental health), interpersonal (reduced isolation, friendships), community (reciprocity, reduced stigma and discrimination), and structural (housing, employment, immigration, health care) levels. CONCLUSIONS: Findings suggest that social support groups tailored for LGBT African and Caribbean newcomers and refugees can address social isolation, community resilience, and enhance resource access. Health care providers can provide support groups, culturally and LGBT competent health services, and resource access to promote LGBT newcomers and refugees’ health and wellbeing
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