Overdiagnosis in organised mammography screening in Denmark. A comparative study

<p>Abstract</p> <p>Background</p> <p>Overdiagnosis in cancer screening is the detection of cancer lesions that would otherwise not have been detected. It is arguably the most important harm. We quantified overdiagnosis in the Danish mammography screening programme, which is uniquely suited for this purpose, as only 20% of the Danish population has been offered organised mammography screening over a long time-period.</p> <p>Methods</p> <p>We collected incidence rates of carcinoma in situ and invasive breast cancer in areas with and without screening over 13 years with screening (1991-2003), and 20 years before its introduction (1971-1990). We explored the incidence increase comparing unadjusted incidence rates and used Poisson regression analysis to compensate for the background incidence trend, variation in age distribution and geographical variation in incidence.</p> <p>Results</p> <p>For the screened age group, 50 to 69 years, we found an overdiagnosis of 35% when we compared unadjusted incidence rates for the screened and non-screened areas, but after compensating for a small decline in incidence in older, previously screened women. Our adjusted Poisson regression analysis indicated a relative risk of 1.40 (95% CI: 1.35-1.45) for the whole screening period, and a potential compensatory drop in older women of 0.90 (95% CI: 0.88-0.96), yielding an overdiagnosis of 33%, which we consider the most reliable estimate. The drop in previously screened women was only present in one of the two screened regions and was small in absolute numbers.</p> <p>Discussion</p> <p>One in four breast cancers diagnosed in the screened age group in the Danish screening programme is overdiagnosed. Our estimate for Denmark is lower than that for comparable countries, likely because of lower uptake, lower recall rates and lower detection rates of carcinoma in situ.</p

Metabolic flexibility as a major predictor of spatial distribution in microbial communities

A better understand the ecology of microbes and their role in the global ecosystem could be achieved if traditional ecological theories can be applied to microbes. In ecology organisms are defined as specialists or generalists according to the breadth of their niche. Spatial distribution is often used as a proxy measure of niche breadth; generalists have broad niches and a wide spatial distribution and specialists a narrow niche and spatial distribution. Previous studies suggest that microbial distribution patterns are contrary to this idea; a microbial generalist genus (Desulfobulbus) has a limited spatial distribution while a specialist genus (Methanosaeta) has a cosmopolitan distribution. Therefore, we hypothesise that this counter-intuitive distribution within generalist and specialist microbial genera is a common microbial characteristic. Using molecular fingerprinting the distribution of four microbial genera, two generalists, Desulfobulbus and the methanogenic archaea Methanosarcina, and two specialists, Methanosaeta and the sulfate-reducing bacteria Desulfobacter were analysed in sediment samples from along a UK estuary. Detected genotypes of both generalist genera showed a distinct spatial distribution, significantly correlated with geographic distance between sites. Genotypes of both specialist genera showed no significant differential spatial distribution. These data support the hypothesis that the spatial distribution of specialist and generalist microbes does not match that seen with specialist and generalist large organisms. It may be that generalist microbes, while having a wider potential niche, are constrained, possibly by intrageneric competition, to exploit only a small part of that potential niche while specialists, with far fewer constraints to their niche, are more capable of filling their potential niche more effectively, perhaps by avoiding intrageneric competition. We suggest that these counter-intuitive distribution patterns may be a common feature of microbes in general and represent a distinct microbial principle in ecology, which is a real challenge if we are to develop a truly inclusive ecology

Are benefits and harms in mammography screening given equal attention in scientific articles? A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The CONSORT statement specifies the need for a balanced presentation of both benefits and harms of medical interventions in trial reports. However, invitations to screening and newspaper articles often emphasize benefits and downplay or omit harms, and it is known that scientific articles can be influenced by conflicts of interest. We wanted to determine if a similar imbalance occurs in scientific articles on mammography screening and if it is related to author affiliation.</p> <p>Methods</p> <p>We searched PubMed in April 2005 for articles on mammography screening that mentioned a benefit or a harm and that were published in 2004 in English. Data extraction was performed by three independent investigators, two unblinded and one blinded for article contents, and author names and affiliation, as appropriate. The extracted data were compared and discrepancies resolved by two investigators in a combined analysis. We defined three groups of authors: (1) authors in specialties unrelated to mammography screening, (2) authors in screening-affiliated specialties (radiology or breast cancer surgery) who were not working with screening, or authors funded by cancer charities, and (3) authors (at least one) working directly with mammography screening programmes. We used a data extraction sheet with 17 items described as important benefits and harms in the 2002 WHO/IARC-report on breast cancer screening.</p> <p>Results</p> <p>We identified 854 articles, and 143 were eligible for the study. Most were original research. Benefits were mentioned more often than harms (96% vs 62%, P < 0.001). Fifty-five (38%) articles mentioned only benefits, whereas seven (5%) mentioned only harms (P < 0.001). Overdiagnosis was mentioned in 35 articles (24%), but was more often downplayed or rejected in articles that had authors working with screening, (6/15; 40%) compared with authors affiliated by specialty or funding (1/6; 17%), or authors unrelated with screening (1/14; 7%) (P = 0.03). Benefits in terms of reduced breast cancer mortality were mentioned in 109 (76%) articles, and was more often provided as a relative risk reduction than an absolute risk reduction, where quantified (45 articles (31%) versus 6 articles (3%) (P < 0.001)).</p> <p>Conclusion</p> <p>Scientific articles tend to emphasize the major benefits of mammography screening over its major harms. This imbalance is related to the authors' affiliation.</p

Shaping the global communications milieu : the EU's influence on internet and telecommunications governance

This article evaluates the European Union's (EU) influence in shaping the global governance for telecommunications and the Internet. Through analysing EU behaviour within an actorness framework, we demonstrate how the external opportunity structure and the EU's internal environment has impacted on its ability to exert and maximize its presence in order to meet its goals and aims in these two very different sub-sectors of global communications in terms of evolution and development. Such a comparison of EU actorness, we argue, is revealing in terms of uncovering the underlying factors and conditions that allow the EU to influence two important and dynamic communications sub-sectors

Implications of Central Obesity-Related Variants in LYPLAL1, NRXN3, MSRA, and TFAP2B on Quantitative Metabolic Traits in Adult Danes

Two meta-analyses of genome-wide association studies (GWAS) have suggested that four variants: rs2605100 in lysophospholipase-like 1 (LYPLAL1), rs10146997 in neuroxin 3 (NRXN3), rs545854 in methionine sulfoxide reductase A (MSRA), and rs987237 in transcription factor activating enhancer-binding protein 2 beta (TFAP2B) associate with measures of central obesity. To elucidate potential underlying phenotypes we aimed to investigate whether these variants associated with: 1) quantitative metabolic traits, 2) anthropometric measures (waist circumference (WC), waist-hip ratio, and BMI), or 3) type 2 diabetes, and central and general overweight and obesity.The four variants were genotyped in Danish individuals using KASPar®. Quantitative metabolic traits were examined in a population-based sample (n = 6,038) and WC and BMI were furthermore analyzed in a combined study sample (n = 13,507). Case-control studies of diabetes and adiposity included 15,326 individuals. The major G-allele of LYPLAL1 rs2605100 associated with increased fasting serum triglyceride concentrations (per allele effect (β) = 3%(1;5(95%CI)), p(additive) = 2.7×10(-3)), an association driven by the male gender (p(interaction) = 0.02). The same allele associated with increased fasting serum insulin concentrations (β = 3%(1;5), p(additive) = 2.5×10(-3)) and increased insulin resistance (HOMA-IR) (β = 4%(1;6), p(additive) = 1.5×10(-3)). The minor G-allele of rs10146997 in NRXN3 associated with increased WC among women (β = 0.55cm (0.20;0.89), p(additive) = 1.7×10(-3), p(interaction) = 1.0×10(-3)), but showed no associations with obesity related metabolic traits. The MSRA rs545854 and TFAP2B rs987237 showed nominal associations with central obesity; however, no underlying metabolic phenotypes became obvious, when investigating quantitative metabolic traits. None of the variants influenced the prevalence of type 2 diabetes.We demonstrate that several of the central obesity-associated variants in LYPLAL1, NRXN3, MSRA, and TFAP2B associate with metabolic and anthropometric traits in Danish adults. However, analyses were made without adjusting for multiple testing, and further studies are needed to confirm the putative role of LYPLAL1, NRXN3, MSRA, and TFAP2B in the pathophysiology of obesity

Evaluation of Functional Erythropoietin Receptor Status in Skeletal Muscle In Vivo: Acute and Prolonged Studies in Healthy Human Subjects

BACKGROUND: Erythropoietin receptors have been identified in human skeletal muscle tissue, but downstream signal transduction has not been investigated. We therefore studied in vivo effects of systemic erythropoietin exposure in human skeletal muscle. METHODOLOGY/PRINCIPAL FINDINGS: The protocols involved 1) acute effects of a single bolus injection of erythropoietin followed by consecutive muscle biopsies for 1-10 hours, and 2) a separate study with prolonged administration for 16 days with biopsies obtained before and after. The presence of erythropoietin receptors in muscle tissue as well as activation of Epo signalling pathways (STAT5, MAPK, Akt, IKK) were analysed by western blotting. Changes in muscle protein profiles after prolonged erythropoietin treatment were evaluated by 2D gel-electrophoresis and mass spectrometry. The presence of the erythropoietin receptor in skeletal muscle was confirmed, by the M20 but not the C20 antibody. However, no significant changes in phosphorylation of the Epo-R, STAT5, MAPK, Akt, Lyn, IKK, and p70S6K after erythropoietin administration were detected. The level of 8 protein spots were significantly altered after 16 days of rHuEpo treatment; one isoform of myosin light chain 3 and one of desmin/actin were decreased, while three isoforms of creatine kinase and two of glyceraldehyd-3-phosphate dehydrogenase were increased. CONCLUSIONS/SIGNIFICANCE: Acute exposure to recombinant human erythropoietin is not associated by detectable activation of the Epo-R or downstream signalling targets in human skeletal muscle in the resting situation, whereas more prolonged exposure induces significant changes in the skeletal muscle proteome. The absence of functional Epo receptor activity in human skeletal muscle indicates that the long-term effects are indirect and probably related to an increased oxidative capacity in this tissue

Genome-Wide Population-Based Association Study of Extremely Overweight Young Adults – The GOYA Study

Background: Thirty-two common variants associated with body mass index (BMI) have been identified in genome-wide association studies, explaining ~1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched for extremely overweight individuals. We aimed to identify new loci associated with BMI and to ascertain whether using an extreme sampling design would identify the variants known to be associated with BMI in general populations. Methodology/Principal Findings: From two large Danish cohorts we selected all extremely overweight young men and women (n = 2,633), and equal numbers of population-based controls (n = 2,740, drawn randomly from the same populations as the extremes, representing ~212,000 individuals). We followed up novel (at the time of the study) association signals (

Community compensation in the context of Carbon Capture and Storage: Current debates and practices

Societal opposition has the potential to slow down the implementation of Carbon Capture and Storage (CCS). One of the difficulties is that the perceived benefits associated with a CCS facility for local communities tend to be low compared to its perceived burdens. As is the case for other low carbon technologies, community compensation (or community benefits) has been suggested as a way to restore this perceived imbalance. A diverse literature has looked into the role of community compensation across various land uses and research fields. Synthesis is limited, while at the same time, the provision of community compensation in practice is moving from an ad hoc to a more institutionalized approach. Therefore, it is important to take stock of the literature. This paper provides a review of the community compensation literature in the form of four debates, drawing together environmental social science research on different low carbon technologies (e.g. CCS, renewable energy). In addition, current practices in community compensation for four European countries are discussed. The two parts of this paper are brought together in a set of lessons for the provision of community compensation for future CCS projects; in turn, suggestions for further research are made to address remaining knowledge gaps