Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
Electron paramagnetic resonance of single-walled carbon nanotubes (SWCNTs) has been bedevilled by the presence of paramagnetic impurities. To address this, SWCNTs produced by laser ablation with a nonmagnetic PtRhRe catalyst were purified through a multiple step centrifugation process in order to remove amorphous carbon and catalyst impurities. Centrifugation of a SWCNT solution resulted in sedimentation of carbon nanotube bundles containing clusters of catalyst particles, while isolated nanotubes with reduced catalyst particle content remained in the supernatant. Further ultracentrifugation resulted in highly purified SWCNT samples with a narrow diameter distribution and almost no detectable catalyst particles. Electron paramagnetic resonance (EPR) signals were detected only for samples which contained catalyst particles, with the ultracentrifuged SWCNTs showing no EPR signal at X-band (9.4 GHz) and fields < 0.4 T.
BackgroundDespite the great burden of chronic respiratory diseases in China, few large multicentre, spirometry-based studies have examined its prevalence, rate of underdiagnosis regionally or the relevance of socioeconomic and lifestyle factors.MethodsWe analysed data from 512 891 adults in the China Kadoorie Biobank, recruited from 10 diverse regions of China during 2004–2008. Air flow obstruction (AFO) was defined by the lower limit of normal criteria based on spirometry-measured lung function. The prevalence of AFO was analysed by region, age, socioeconomic status, body mass index (BMI) and smoking history and compared with the prevalence of self-reported physician-diagnosed chronic bronchitis or emphysema (CB/E) and its symptoms.FindingsThe prevalence of AFO was 7.3% in men (range 2.5–18.2%) and 6.4% in women (1.5–18.5%). Higher prevalence of AFO was associated with older age (p<0.0001), lower income (p<0.0001), poor education (p<0.001), living in rural regions (p<0.001), those who started smoking before the age of 20 years (p<0.001) and low BMI (p<0.001). Compared with self-reported diagnosis of CB/E, 88.8% of AFO was underdiagnosed; underdiagnosis proportion was highest in 30–39-year olds (96.7%) compared with the 70+ age group (81.1%), in women (90.7%), in urban areas (89.4%), in people earning 5K–10 K ¥ monthly (90.3%) and in those with middle or high school education (92.6%).InterpretationIn China, the burden of AFO based on spirometry was high and significantly greater than that estimated based on self-reported physician-diagnosed CB/E, especially in rural areas, reflecting major issues with diagnosis of AFO that will impact disease treatment and management.
Previous studies have demonstrated long-term changes in effective moisture in subSaharan Africa. Here, we reconstruct Holocene environments using a $7 m lake-sediment sequence recovered from the northeastern Nigerian Sahel and attempt to distinguish basin-specific changes from regional climatic variations. The sequence was analysed for sedimentological properties, mineral magnetism and pollen, and dated by 137 Cs, 210 Pb excess and 14 C. Extremely arid conditions of the terminal Pleistocene ended ca. 11 500 cal. BP (calendar years) when climate ameliorated and a lake developed until the occurrence of an arid event leading to lake desiccation at $11 200 cal. BP. Following this, climate ameliorated and a water body re-emerged. Very wet conditions predominated 11 200-5600 cal. BP, followed by drought between 5600 and 5500 cal. BP and a return to moderate humidity from 5500 to 4000 cal. BP. After 4000 cal. BP, a marked deterioration occurred, culminating in lake desiccation at ca. 800 cal. BP. After this time the climate remained generally dry and the re-emerging lake was shallow. Comparison of these results with other well-dated sequences in the region demonstrates the importance of basin-specific influences on the palaeolimnological records in addition to regional climatic controls. Disentangling these different controls, as well as the reconstruction of Holocene climate, therefore requires a multiple-basin approach.
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