Are there biological differences between screen-detected and interval colorectal cancers in the English Bowel Cancer Screening Programme?

Background: We measured biomarkers of tumour growth and vascularity in interval and screen-detected colorectal cancers (CRCs) in the English Bowel Cancer Screening Programme in order to determine whether rapid tumour growth might contribute to interval CRC (a CRC diagnosed between a negative guaiac stool test and the next scheduled screening episode). Methods: Formalin-fixed, paraffin-embedded sections from 71 CRCs (screen-detected 43, interval 28) underwent immunohistochemistry for CD31 and Ki-67, in order to measure the microvessel density (MVD) and proliferation index (PI), respectively, as well as microsatellite instability (MSI) testing. Results: Interval CRCs were larger (P=0.02) and were more likely to exhibit venous invasion (P=0.005) than screen-detected tumours. There was no significant difference in MVD or PI between interval and screen-detected CRCs. More interval CRCs displayed MSI-high (14%) compared with screen-detected tumours (5%). A significantly (P=0.005) higher proportion (51%) of screen-detected CRC resection specimens contained at least one polyp compared with interval CRC (18%) resections. Conclusions: We found no evidence of biological differences between interval and screen-detected CRCs, consistent with the low sensitivity of guaiac stool testing as the main driver of interval CRC. The contribution of synchronous adenomas to occult blood loss for screening requires further investigation

Nonlinear landscape and cultural response to sea-level rise

Rising sea levels have been associated with human migration and behavioral shifts throughout prehistory, often with an emphasis on landscape submergence and consequent societal collapse. However, the assumption that future sea-level rise will drive similar adaptive responses is overly simplistic. While the change from land to sea represents a dramatic and permanent shift for preexisting human populations, the process of change is driven by a complex set of physical and cultural processes with long transitional phases of landscape and socioeconomic change. Here, we use reconstructions of prehistoric sea-level rise, paleogeographies, terrestrial landscape change, and human population dynamics to show how the gradual inundation of an island archipelago resulted in decidedly nonlinear landscape and cultural responses to rising sea levels. Interpretation of past and future responses to sea-level change requires a better understanding of local physical and societal contexts to assess plausible human response patterns in the future

Urinary biomarker concentrations of captan, chlormequat, chlorpyrifos and cypermethrin in UK adults and children living near agricultural land

There is limited information on the exposure to pesticides experienced by UK residents living near agricultural land. This study aimed to investigate their pesticide exposure in relation to spray events. Farmers treating crops with captan, chlormequat, chlorpyrifos or cypermethrin provided spray event information. Adults and children residing ≤100 m from sprayed fields provided first-morning void urine samples during and outwith the spray season. Selected samples (1–2 days after a spray event and at other times (background samples)) were analysed and creatinine adjusted. Generalised Linear Mixed Models were used to investigate if urinary biomarkers of these pesticides were elevated after spray events. The final data set for statistical analysis contained 1518 urine samples from 140 participants, consisting of 523 spray event and 995 background samples which were analysed for pesticide urinary biomarkers. For captan and cypermethrin, the proportion of values below the limit of detection was greater than 80%, with no difference between spray event and background samples. For chlormequat and chlorpyrifos, the geometric mean urinary biomarker concentrations following spray events were 15.4 μg/g creatinine and 2.5 μg/g creatinine, respectively, compared with 16.5 μg/g creatinine and 3.0 μg/g creatinine for background samples within the spraying season. Outwith the spraying season, concentrations for chlorpyrifos were the same as those within spraying season backgrounds, but for chlormequat, lower concentrations were observed outwith the spraying season (12.3 μg/g creatinine). Overall, we observed no evidence indicative of additional urinary pesticide biomarker excretion as a result of spray events, suggesting that sources other than local spraying are responsible for the relatively low urinary pesticide biomarkers detected in the study population

The Role of Innate APOBEC3G and Adaptive AID Immune Responses in HLA-HIV/SIV Immunized SHIV Infected Macaques

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Eurozone Membership and Foreign Direct Investment

Our aim in this chapter is to estimate the effects of European Monetary Union (EMU) membership on foreign direct investment (FDI). Previous literature on the cross-border impact of a common currency have concentrated on international trade effects. Our analysis is based on the gravity model, which has been successfully applied to explain most forms of bilateral cross-border flows. We estimate a structural gravity model using data for 34 OECD countries between 1985 and 2013 for bilateral FDI. We use a variety of econometric techniques to ensure the robustness of our findings including stock as well as flow measures of FDI and addressing selection issues. Our estimates of the impact of EMU underlines the role of FDI as a channel for benefits from deep economic integration between countries. The effect of EMU membership on FDI is estimated to be significant and positive, at around 130%

Smokers' interest in a lung cancer screening programme: a national survey in England.

Following the recommendation of lung cancer screening in the US, screening committees in several European countries are reviewing the evidence for implementing national programmes. However, inadequate participation from high-risk groups poses a potential barrier to its effectiveness. The present study examined interest in a national lung cancer screening programme and modifiable attitudinal factors that may affect participation by smokers.A population-based survey of English adults (n = 1464; aged 50-70 years) investigated screening intentions in different invitation scenarios, beliefs about lung cancer, early detection and treatment, worry about lung cancer risk, and stigma. Data on smoking status and perceived chances of quitting were also collected, but eligibility for lung screening in the event of a national programme was unknown.Intentions to be screened were high in all three invitation scenarios for both current (≥ 89%) and former (≥ 94%) smokers. However, smokers were less likely to agree that early-stage survival is good (43% vs. 53%; OR: 0.64, 0.46-0.88) or be willing to have surgery for an early stage, screen-detected cancer (84% vs. 94%; OR: 0.38, 0.21-0.68), compared with former smokers. Willingness to have surgery was positively associated with screening intentions; with absolute differences of 25% and 29%. Worry about lung cancer risk was also most common among smokers (48%), and one fifth of respondents thought screening smokers was a waste of NHS money.A national lung cancer screening programme would be well-received in principle. To improve smokers' participation, care should be taken to communicate the survival benefits of early-stage diagnosis, address concerns about surgery, and minimise anxiety and stigma related to lung cancer risk

Search for the decay modes D^0 → e^+e^-, D^0 → μ^+μ^-, and D^0 → e^±μ∓

We present searches for the rare decay modes D^0→e^+e^-, D^0→μ^+μ^-, and D^0→e^±μ^∓ in continuum e^+e^-→cc events recorded by the BABAR detector in a data sample that corresponds to an integrated luminosity of 468  fb^(-1). These decays are highly Glashow–Iliopoulos–Maiani suppressed but may be enhanced in several extensions of the standard model. Our observed event yields are consistent with the expected backgrounds. An excess is seen in the D^0→μ^+μ^- channel, although the observed yield is consistent with an upward background fluctuation at the 5% level. Using the Feldman–Cousins method, we set the following 90% confidence level intervals on the branching fractions: B(D^0→e^+e^-)<1.7×10^(-7), B(D^0→μ^+μ^-) within [0.6,8.1]×10^(-7), and B(D^0→e^±μ^∓)<3.3×10^(-7)