Acceptability of aspirin for cancer preventive therapy: a survey and qualitative study exploring the views of the UK general population

Objectives Aspirin could be offered for colorectal cancer prevention for the UK general population. To ensure the views of the general population are considered in future guidance, we explored public perceptions of aspirin for preventive therapy. Design We conducted an online survey to investigate aspirin use, and awareness of aspirin for cancer prevention among the UK general population. We conducted semistructured interviews with a subsample of survey respondents to explore participants’ acceptability towards aspirin for cancer preventive therapy. We analysed the interview data using reflexive thematic analysis and mapped the themes onto the Theoretical Domains Framework, and the Necessity and Concerns Framework. Setting Online survey and remote interviews. Participants We recruited 400 UK respondents aged 50–70 years through a market research company to the survey. We purposefully sampled, recruited and interviewed 20 survey respondents. Results In the survey, 19.0% (76/400) of respondents were aware that aspirin can be used to prevent cancer. Among those who had previously taken aspirin, 1.9% (4/216) had taken it for cancer prevention. The interviews generated three themes: (1) perceived necessity of aspirin; (2) concerns about side effects; and (3) preferred information sources. Participants with a personal or family history of cancer were more likely to perceive aspirin as necessary for cancer prevention. Concerns about taking aspirin at higher doses and its side effects, such as gastrointestinal bleeding, were common. Many described wanting guidance and advice on aspirin to be communicated from sources perceived as trustworthy, such as healthcare professionals. Conclusions Among the general population, those with a personal or family history of cancer may be more receptive towards taking aspirin for preventive therapy. Future policies and campaigns recommending aspirin may be of particular interest to these groups. Multiple considerations about the benefits and risks of aspirin highlight the need to support informed decisions on the medication

Access of energetic particles to Titan's exobase: a study of Cassini's T9 flyby

We study how the local electromagnetic disturbances introduced by Titan affect the ionization rates of the atmosphere. For this, we model the precipitation of energetic particles, specifically hydrogen and oxygen ions with energies between 1 keV and 1 MeV, into Titan's exobase for the specific magnetospheric configuration of the T9 flyby. For the study, a particle tracing software package is used which consists of an integration of the single particle Lorentz force equation using a 4th order Runge-Kutta numerical method. For the electromagnetic disturbances, the output of the A.I.K.E.F. hybrid code (kinetic ions, fluid electrons) is used, allowing the possibility of analyzing the disturbances and asymmetries in the access of energetic particles originated by their large gyroradii. By combining these methods, 2D maps showing the access of each set of particles were produced. We show that the access of different particles is largely dominated by their gyroradii, with the complexity of the maps increasing with decreasing gyroradius, due to the larger effect that local disturbances introduced by the presence of the moon have in the trajectory of the particles with lower energies. We also show that for particles with gyroradii much larger than the moon's radius, simpler descriptions of the electromagnetic environment can reproduce similar results to those obtained when using the full hybrid simulation description, with simple north-south fields being sufficient to reproduce the hybrid code results for O+ ions with energies larger than 10 keV but not enough to reproduce those for H+H+ ions at any of the energies covered in the present study. Finally, by combining the maps created with upstream plasma flow measurements by the MIMI/CHEMS instrument, we are able to estimate normalized fluxes arriving at different selected positions of the moon's exobase. We then use these fluxes to calculate energy deposition and non-dissociative N2 ionization rates for precipitating O+O+ and H+H+ ions and find differences in the ion production rates of up to almost 80% at the selected positions. All these results combined show that the electromagnetic field disturbances present in the vicinity of Titan significantly affect the contribution of energetic ions to local ionization profiles

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

Comparison of two different strategies for human monocyte subsets gating within the large-scale prospective CARE FOR HOMe Study.

Monocytes are heterogeneous cells consisting of (at least) three subsets: classical, intermediate, and nonclassical monocytes. Correct enumeration of cell counts necessitates well-defined gating strategies, which are essentially based upon CD14 and CD16 expression. For the delineation of intermediate from nonclassical monocytes, a &quot;rectangular gating (RG) strategy&quot; and a &quot;trapezoid gating (TG) strategy&quot; have been proposed. We compared the two gating strategies in a well-defined clinical cohort of patients with chronic kidney disease (CKD). Within the ongoing CARE FOR HOMe study, monocyte subsets were reanalyzed in 416 CKD patients, who were followed 3.6&thinsp;&plusmn;&thinsp;1.6 years for the occurrence of a cardiovascular event. Gating was performed by either RG or TG. We analyzed the expression of surface markers, and compared the predictive role of cell counts of monocyte subsets, as defined by RG and TG, respectively. With both gating strategies, higher intermediate monocyte counts predicted the cardiovascular endpoint in Kaplan-Meier analyses (P&thinsp;&lt;&thinsp;0.001 with RG; P&thinsp;&lt;&thinsp;0.001 with TG). After correction for confounders, intermediate monocyte counts remained independent predictors in Cox-Regression analyses (HR&thinsp;=&thinsp;1.013 [95% CI: 1.006-1.020; P&thinsp;&lt;&thinsp;0.001] with RG; HR&thinsp;=&thinsp;1.015 [95% CI: 1.006-1.024; P&thinsp;=&thinsp;0.001] with TG). NRI was 3.9% when reclassifying patients from quartiles of intermediate monocyte counts with RG strategy toward quartiles of intermediate monocytes counts with TG strategy. In expression analysis, those monocytes which are defined as intermediate monocytes by the RG strategy and as nonclassical monocytes by the TG strategy share characteristics of both subsets. In conclusion, intermediate monocytes were independent predictors of cardiovascular outcome irrespective of the applied gating strategy. Future studies should aim to identify markers that allow for an unequivocal definition of intermediate monocytes, which may further improve their power to predict cardiovascular events

A simplified method to assess affinity of insulin autoantibodies.

Insulin autoantibodies (IAA) precede type 1 diabetes, but not all IAA-positive children develop other islet autoantibodies and disease. Diabetes risk can be stratified by laborious IAA affinity measurement using competition with multiple ligand concentrations. Here, we identify a single competitor concentration that discriminates low- and high-affinity IAA. Discrimination was achieved among 122 IAA-positive sera using 7.0 nM competitor which is 54-fold that of the assay radioligand concentration. Relative-binding &lt;60% at this competitor concentration identified all 85 sera with affinities &ge;1.0&times;10⁸ L/mol and none with lower affinities (P&lt;0.0001), and 45 (96%) of 47 multiple islet autoantibody-positive sera (P&lt;0.0001). IAA competition was further tested in a second set of 119 IAA-positive sera. Of these, 99 fulfilled high-affinity competition criteria of &lt;60% relative-binding at 7.0 nM competitor including 89 (94%) of 95 sera with multiple islet autoantibodies (P&lt;0.0001). Thus, increased IAA specificity can be achieved with simple modification to existing assays