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Background: This supplement presents a wide range of observations, reviews, novel research and analyses underpinning the National Awareness and Early Diagnosis Initiative (NAEDI). The preceding three papers present and discuss different aspects of the data from European cancer survival comparison studies. I conclude here by attempting to quantify the extent to which delayed diagnosis in England accounts for observed survival differences and by outlining areas for further research. Methods: Analysis of indirect evidence related to late diagnosis, surgical intervention rates and utilisation of radiotherapy and chemotherapy in England and other European countries in the late 1990s for breast, colorectal and lung cancer. Results: Late diagnosis was almost certainly a major contributor to poor survival in England for all three cancers. Low surgical intervention rates are very likely to have contributed to low survival rates for lung cancer and possibly for the other two cancers. Any differences in the use of radiotherapy or chemotherapy are likely to have had only a minor impact on survival differences. Conclusion: Between 5000 and 10000 deaths within 5 years of diagnosis could be avoided every year in England if efforts to promote earlier diagnosis and appropriate primary surgical treatment are successful. Detailed international benchmarking studies are to be recommended.

Background: The United Kingdom has poorer cancer outcomes than many other countries due partly to delays in diagnosing symptomatic cancer, leading to more advanced stage at diagnosis. Delays can occur at the level of patients, primary care, systems and secondary care. There is considerable potential for interventions to minimise delays and lead to earlier-stage diagnosis. Methods: Scoping review of the published studies, with a focus on methodological issues. Results: Trial data in this area are lacking and observational studies often show no association or negative ones. This review offers methodological explanations for these counter-intuitive findings. Conclusion: While diagnostic delays do matter, their importance is uncertain and must be determined through more sophisticated methods.

Background: This review of the EUROCARE-4 results attempts to separate out the early and late mortality effects contributing to the widely reported poorer 5-year survival rates for cancer patients in the United Kingdom compared with other European countries for 26 cancer sites. Methods: Patients diagnosed with cancer in 1996–1999 in 23 European countries were included in the analyses. Comparison of 1-year, 5-year and 5∣1-year (i.e. only including those patients who had survived to 1 year) survival estimates between data for England and the ‘European average’ was undertaken. This analysis was to highlight the relative contribution of early diagnosis, using 1-year survival as a proxy measure, on 5-year survival for the different sites of cancer. Three groups of cancer sites were identified according to whether the survival differences at 1, 5 and 5∣1 years were statistically significant. Results and conclusions: Breast cancer showed significantly poorer 1- and 5-year survival estimates in England, but the 5∣1-year survival figure was not significantly different. Thus, successful initiatives around awareness and early detection could eradicate the survival gap. In contrast, the 5∣1-year survival estimates remained significantly worse for lung, colorectal and prostate cancers, showing that although early detection could make some difference, late effects such as treatment and management of the patients were also influencing long-term outcome differences between England and Europe.

Achieving adequate levels of uptake in cancer screening requires a variety of approaches that need to be shaped by the characteristics of both the screening programme and the target population. Strategies to improve uptake typically produce only incremental increases. Accordingly, approaches that combine behavioural, organisational and other strategies are most likely to succeed. In conjunction with a focus on uptake, providers of screening services need to promote informed decision making among invitees. Addressing inequalities in uptake must remain a priority for screening programmes. Evidence informing strategies targeting low-uptake groups is scarce, and more research is needed in this area. Cancer screening has the potential to make a major contribution to early diagnosis initiatives in the United Kingdom, and will best be achieved through uptake strategies that emphasise wide coverage, informed choice and equitable distribution of cancer screening services.

Background: This paper provides a one-page visual summary of the previously published relative survival estimates for 42 types of cancers in 23 countries in Europe. Methods: The cancer patients in these analyses were 15 years or older at the time of their diagnosis in the period 1995–1999. Follow-up was to the end of 2003 and relative survival estimates were computed by the cohort method. Results: The analysis of 1-year survival had good discriminatory power and visibly separated a group of countries with consistently high survival estimates (Switzerland, France, Sweden, Belgium and Italy) and another group of countries with lower estimates (Poland, Czech Republic, Ireland, Denmark and United Kingdom–Northern Ireland). After the first year, there was less variation between the countries. Conclusion: To more fully understand the UK situation, a rational comparison would select countries with data-quality, prosperity and healthcare systems that are similar to the United Kingdom. In otherwise comparable populations, a pronounced difference in 1-year survival is most likely to be due to variation in a strong prognostic factor, which exerts its effect in the short term. A likely explanation for the short-term survival deficit in the United Kingdom compared with the Nordic countries is a less favourable stage distribution in the United Kingdom. However, the present superficial analysis does not exclude possible functions for other factors relating to the organisation and quality of cancer care services.

The thermal and therefore physical state of magma bodies within the crust controls the processes and time scales required to mobilize magmas before eruptions, which in turn are critical to hazard assessment. Crystal records can be used to reconstruct magma reservoir histories, and the resulting time and length scales are converging with those accessible through numerical modelling of magma system dynamics. The goal of this contribution is to summarize constraints derived from crystal chronometry (radiometric dating and modelling intracrystalline diffusion durations), in order to facilitate use of these data by researchers in other fields. Crystallization ages of volcanic minerals typically span a large range (10 4 –10 5  years), recording protracted activity in a given magma reservoir. However, diffusion durations are orders of magnitude shorter, indicating that the final mixing and assembly of erupted magma bodies is rapid. Combining both types of data in the same samples indicates that crystals are dominantly stored at near- or sub-solidus conditions, and are remobilized rapidly prior to eruptions. These observations are difficult to reconcile with some older numerical models of magma reservoir dynamics. However, combining the crystal-scale observations with models which explicitly incorporate grain-scale physics holds great potential for understanding dynamics within crustal magma reservoirs. This article is part of the Theo Murphy meeting issue ‘Magma reservoir architecture and dynamics’.

ObjectivesTo assess how to control, detect, and treat secondary caries. This review serves to inform a joint ORCA/EFCD consensus process.MethodsSystematic and non-systematic reviews were performed or consulted and narratively synthesized.ResultsSecondary (or recurrent) caries is defined as a lesion associated with restorations or sealants. While the restorative material itself has some influence on secondary caries, further factors like the presence and size of restoration gaps, patients’ caries risk, and the placing dentist’s experience seem more relevant. Current detection methods for secondary caries are only sparsely validated and likely prone for the risk of over-detection. In many patients, it might be prudent to prioritize specific detection methods to avoid invasive overtreatment. Detected secondary caries can be managed either by repair of the defective part of the restoration or its complete replacement.ConclusionsThere is sparse data towards the nature of secondary caries and how to control, detect, and treat it.Clinical significanceDespite often claimed to be a major complication of restorations, there is surprisingly little data on secondary caries. Longer-term studies may be needed to identify differences in secondary caries risk between materials and to identify characteristic features of progressive lesions (i.e., those in need of treatment).

Publication bias is a serious problem in systematic reviews and meta-analyses, which can affect the validity and generalization of conclusions. Currently, approaches to dealing with publication bias can be distinguished into two classes: selection models and funnel-plot-based methods. Selection models use weight functions to adjust the overall effect size estimate and are usually employed as sensitivity analyses to assess the potential impact of publication bias. Punnel-plot-based methods include visual examination of a funnel plot, regression and rank tests, and the nonparametric trim and fill method. Although these approaches have been widely used in applications, measures for quantifying publication bias are seldom studied in the literature. Such measures can be used as a characteristic of a meta-analysis; also, they permit comparisons of publication biases between different meta-analyses. Egger's regression intercept may be considered as a candidate measure, but it lacks an intuitive interpretation. This article introduces a new measure, the skewness of the standardized deviates, to quantify publication bias. This measure describes the asymmetry of the collected studies' distribution. In addition, a new test for publication bias is derived based on the skewness. Large sample properties of the new measure are studied, and its performance is illustrated using simulations and three case studies.