Risk Factors for Colorectal Cancer in Patients with Multiple Serrated Polyps: A Cross-Sectional Case Series from Genetics Clinics

Patients with multiple serrated polyps are at an increased risk for developing colorectal cancer (CRC). Recent reports have linked cigarette smoking with the subset of CRC that develops from serrated polyps. The aim of this work therefore was to investigate the association between smoking and the risk of CRC in high-risk genetics clinic patients presenting with multiple serrated polyps. Methods and Findings We identified 151 Caucasian individuals with multiple serrated polyps including at least 5 outside the rectum, and classified patients into non-smokers, current or former smokers at the time of initial diagnosis of polyposis. Cases were individuals with multiple serrated polyps who presented with CRC. Controls were individuals with multiple serrated polyps and no CRC. Multivariate logistic regression was performed to estimate associations between smoking and CRC with adjustment for age at first presentation, sex and co-existing traditional adenomas, a feature that has been consistently linked with CRC risk in patients with multiple serrated polyps. CRC was present in 56 (37%) individuals at presentation. Patients with at least one adenoma were 4 times more likely to present with CRC compared with patients without adenomas (OR = 4.09; 95%CI 1.27 to 13.14; P = 0.02). For females, the odds of CRC decreased by 90% in current smokers as compared to never smokers (OR = 0.10; 95%CI 0.02 to 0.47; P = 0.004) after adjusting for age and adenomas. For males, there was no relationship between current smoking and CRC. There was no statistical evidence of an association between former smoking and CRC for both sexes. Conclusion A decreased odds for CRC was identified in females with multiple serrated polyps who currently smoke, independent of age and the presence of a traditional adenoma. Investigations into the biological basis for these observations could lead to non-smoking-related therapies being developed to decrease the risk of CRC and colectomy in these patients.Daniel D. Buchanan, Kevin Sweet, Musa Drini, Mark A. Jenkins, Aung Ko Win, Dallas R. English, Michael D. Walsh, Mark Clendenning, Diane M. McKeone, Rhiannon J. Walters, Aedan Roberts, Sally-Ann Pearson, Erika Pavluk, John L. Hopper, Michael R. Gattas, Jack Goldblatt, Jill George, Graeme K. Suthers, Kerry D. Phillips, Sonja Woodal, Julie Arnold, Kathy Tucker, Amanda Muir, Michael Field, Sian Greening, Steven Gallinger, Renee Perrier, John A. Baron, John D. Potter, Robert Haile, Wendy Franke, Albert de la Chapelle, Finlay Macrae, Christophe Rosty, Neal I. Walker, Susan Parry and Joanne P. Youn

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

On the coupling between unstable magnetospheric particle populations and resonant high m ULF wave signatures in the ionosphere

Many theories state that Ultra Low Frequency (ULF) waves with a high azimuthal wave number (m) have their energy source in wave-particle interactions, yet this assumption has been rarely tested numerically and thus many questions still remain as to the waves' exact generation mechanism. For the first time, this paper investigates the cause and effect relationship between the driving magnetospheric particle populations and the ULF wave signatures as observed in the conjugate ionosphere by quantitatively examining the energy exchange that occurs. Firstly, a Monte Carlo method is used to demonstrate statistically that the particle populations observed during conjugate ionospheric high m wave events have more free energy available than populations extracted at random. Secondly, this paper quantifies the energy transferred on a case study basis, for two classes of high m waves, by examining magnetospheric Ion Distribution Functions, (IDFs) and directly comparing these with the calculated wave energy dissipated into the conjugate ionosphere. Estimates of the wave energy at the source and the sink are in excellent agreement, with both being of the order of 1010J for a typical high m wave. Ten times more energy (1011J) is transferred from the magnetospheric particle population and dissipated in the ionosphere when considering a subset of high m waves known as giant pulsations (Pgs). Previous work has demonstrated that 1010J is frequently available from non - Maxwellian IDFs at L=6, whereas 1011J is not. The combination of these studies thus provides an explanation for both the rarity of Pgs and the ubiquity of other high m waves in this region.</p

Multi-Instrument Observations of the Effects of a Solar Wind Pressure Pulse on the High Latitude Ionosphere: A Detailed Case Study of a Geomagnetic Sudden Impulse

The effects of a solar wind pressure pulse on the terrestrial magnetosphere have been observed in detail across multiple datasets. The communication of these effects into the magnetosphere is known as a positive geomagnetic sudden impulse (+SI), and are observed across latitudes and different phenomena to characterize the propagation of +SI effects through the magnetosphere. A superposition of Alfvén and compressional propagation modes are observed in magnetometer signatures, with the dominance of these signatures varying with latitude. For the first time, collocated lobe reconnection convection vortices and region 0 field aligned currents are observed preceding the +SI onset, and an enhancement of these signatures is observed as a result of +SI effects. Finally, cusp auroral emission is observed collocated with the convection and current signatures. For the first time, simultaneous observations across multiple phenomena are presented to confirm models of +SI propagation presented previously