ALBERT

Description: Background Postmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location. Methods We pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, pathway: adenoma-carcinoma, alternate, serrated), tumor location (proximal colon, distal colon, rectum), and HT use among 8220 postmenopausal women (3898 CRC cases and 4322 controls) from 8 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of ever vs never HT use with each tumor subtype compared with controls. Models were adjusted for study, age, body mass index, smoking status, and CRC family history. All statistical tests were 2-sided. Results Among postmenopausal women, ever HT use was associated with a 38% reduction in overall CRC risk (OR =0.62, 95% CI = 0.56 to 0.69). This association was similar according to microsatellite instability, CpG island methylator phenotype and BRAF or KRAS status. However, the association was attenuated for tumors arising through the serrated pathway (OR = 0.81, 95% CI = 0.66 to 1.01) compared with the adenoma-carcinoma pathway (OR = 0.63, 95% CI = 0.55 to 0.73; Phet =.04) and alternate pathway (OR = 0.61, 95% CI = 0.51 to 0.72). Additionally, proximal colon tumors had a weaker association (OR = 0.71, 95% CI = 0.62 to 0.80) compared with rectal (OR = 0.54, 95% CI = 0.46 to 0.63) and distal colon (OR = 0.57, 95% CI = 0.49 to 0.66; Phet =.01) tumors. Conclusions We observed a strong inverse association between HT use and overall CRC risk, which may predominantly reflect a benefit of HT use for tumors arising through the adenoma-carcinoma and alternate pathways as well as distal colon and rectal tumors.

Description: MCA-1B (also called UIT003) is a luminous hot star in the western outskirts of M33, classified over 20 yr ago with a spectral type of Ofpe/WN9 and identified then as a candidate luminous blue variable (LBV). Palomar Transient Factory data reveal that this star brightened in 2010, with a light curve resembling that of the classic LBV star AF And in M31. Other Ofpe/WN9 stars have erupted as LBVs, but MCA-1B was unusual because it remained hot. It showed a WN-type spectrum throughout its eruption, whereas LBVs usually get much cooler. MCA-1B showed an almost four-fold increase in bolometric luminosity and a doubling of its radius, but its temperature stayed ≳29 kK. As it faded, it shifted to even hotter temperatures, exhibiting a WN7/WN8-type spectrum, and doubling its wind speed. MCA-1B is reminiscent of some supernova impostors, and its location resembles the isolated environment of SN 2009ip. It is most similar to HD 5980 (in the Small Magellanic Cloud) and GR 290 (also in M33). Whereas these two LBVs exhibited B-type spectra in eruption, MCA-1B is the first clear case where a Wolf–Rayet (WR) spectrum persisted at all times. Together, MCA-1B, HD 5980, and GR 290 constitute a class of WN-type LBVs, distinct from S Doradus LBVs. They are most interesting in the context of LBVs at low metallicity, a possible post-LBV/WR transition in binaries, and as likely Type Ibn supernova progenitors.

Description: Background We previously investigated the association between five ‘first-generation’ measures of epigenetic aging and cancer risk in the Melbourne Collaborative Cohort Study. The present study assessed cancer risk associations for three recently developed methylation-based biomarkers of aging: PhenoAge, GrimAge, and predicted telomere length. Methods We estimated rate ratios (RRs) for the association between these three age-adjusted measures and risk of colorectal (N = 813), gastric (N = 165), kidney (N = 139), lung (N = 327), mature B-cell (N = 423), prostate (N = 846) and urothelial (N = 404) cancer, using conditional logistic regression models. We also assessed associations by time since blood draw and by cancer subtype, and investigated potential non-linearity. Results We observed relatively strong associations of age-adjusted PhenoAge with risk of colorectal, kidney, lung, mature B-cell, and urothelial cancers (RR per standard deviation [SD]was approximately 1.2–1.3). Similar findings were obtained for age-adjusted GrimAge, but the association with lung cancer risk was much larger after adjustment for smoking status, pack-years, starting age, time since quitting and other cancer risk factors (RR per SD = 1.82, 95%CI = 1.44–2.30). Most associations appeared linear, larger than for the first-generation measures, and were virtually unchanged after adjustment for a large set of sociodemographic, lifestyle and anthropometric variables. For cancer overall, the comprehensively-adjusted RR per SD was 1.13 (95%CI = 1.07–1.19) for PhenoAge and 1.12 (95%CI = 1.05–1.20) for GrimAge, and appeared larger within 5 years of blood draw (RR = 1.29, 95%CI = 1.15–1.44 and 1.19, 95%CI = 1.06–1.33, respectively). Conclusion The methylation-based measures PhenoAge and GrimAge may provide insights into the relationship between biological aging and cancer and be useful to predict cancer risk, particularly for lung cancer.

Description: Summary The Pacific Coast of Central North America is a geodynamically complex region which has been subject to various geophysical processes operating on different time scales. Glacial isostatic adjustment (GIA), the ongoing deformational response of the solid Earth to past deglaciation, is an important geodynamic process in this region. In this study we apply Earth models with 3D structure to determine if the inclusion of lateral structure can explain the poor performance of 1D models in this region. Three different approaches are used to construct 3D models of the Earth structure. For the first approach, we adopt an optimal 1D viscosity structure from previous work and add lateral variations based on four global seismic shear wave velocity anomalies and two global lithosphere thickness models. The results based on these models indicate that the addition of lateral structure significantly impacts modelled RSL changes, but the data-model fits are not improved. The global seismic models are limited in spatial resolution and so two other approaches were considered to produce higher resolution models of 3D structure: inserting a regional seismic model into two of the global seismic models and, explicitly incorporating regional structure of the Cascadia subduction zone and vicinity, i.e. the subducting slab, the overlying mantle wedge, and the plate boundary interface. The results associated with these higher resolution models do not reveal any clear improvement in satisfying the RSL observations, suggesting that our estimates of lateral structure are inaccurate and/or the data-model misfits are primarily due to limitations in the adopted ice-loading histories. The different realisations of 3D Earth structure gives useful insight to uncertainty associated with this aspect of the GIA model. Our results indicate that improving constraints on the deglacial history of the southwest sector of the Cordilleran ice sheet is an important step towards developing more accurate of GIA models for this region.

Description: We present photometry, spectra, and spectropolarimetry of supernova (SN) 2014ab, obtained through ∼200 d after peak brightness. SN 2014ab was a luminous Type IIn SN (MV 〈 −19.14 mag) discovered after peak brightness near the nucleus of its host galaxy, VV 306c. Pre-discovery upper limits constrain the time of explosion to within 200 d prior to discovery. While SN 2014ab declined by ∼1 mag over the course of our observations, the observed spectrum remained remarkably unchanged. Spectra exhibit an asymmetric emission-line profile with a consistently stronger blueshifted component, suggesting the presence of dust or a lack of symmetry between the far side and near side of the SN. The Pa β emission line shows a profile very similar to that of H α, implying that this stronger blueshifted component is caused either through obscuration by large dust grains, occultation by optically thick material, or a lack of symmetry between the far side and near side of the interaction region. Despite these asymmetric line profiles, our spectropolarimetric data show that SN 2014ab has little detected polarization after accounting for the interstellar polarization. We are likely seeing emission from a photosphere that has only small deviation from circular symmetry in the plane normal to our line of sight, but with either large-grain dust or significant asymmetry in the density of circumstellar material or SN ejecta along our line of sight. We suggest that SN 2014ab and SN 2010jl (as well as other SNe IIn) may be events with similar geometry viewed from different directions.

Description: The cratonic lithosphere–asthenosphere boundary is commonly invoked as the site of sheared peridotite and megacryst formation, a well-recognized petrological assemblage whose genetic relationships—if any—remain poorly understood. We have undertaken a comprehensive petrology and Sr–Nd–Hf–Ca isotope study of sheared peridotite xenoliths and clinopyroxene megacrysts from the c. 1150 Ma Premier kimberlite pipe on the central Kaapvaal craton in South Africa. New textural and mineral trace element evidence suggests that strong tectonic and magmatic overprinting affected the lower cratonic mantle over a vertical distance of ≥50 km from the lithosphere–asthenosphere boundary located at ∼200–225 km depth. Although modification of the central Kaapvaal cratonic mantle is commonly linked to the c. 2056 Ma Bushveld large igneous event, our thermobarometry, mantle redox, and Sr–Nd–Hf–Ca isotope data support a model in which volatile-rich low-volume melts and associated high-density fluids refertilized the lithosphere base shortly before or during asthenosphere-derived kimberlite and carbonatite magmatism at around 1150 Ma. This episode of lithospheric mantle enrichment was facilitated by exceptionally strong shear movements, as are recorded in the plastically deformed peridotites. We argue that stress-driven segregation of percolating carbonated melts contributed to megacryst formation along, or in close proximity to, shear zones within the cratonic mantle lithosphere. Integration of our results from the Kaapvaal craton and modern petrological concepts allows for the identification of a lithosphere–asthenosphere transition zone between ∼150 and 225 km depth. This horizon is defined by intersections of the ∼40–42 mW m–2 Premier paleogeotherm with (1) CO2–H2O-present solidus curves for peridotite (upper bound), and (2) typical mantle adiabats with potential temperatures between 1315 and 1420 °C (lower bound). At Premier, the most strongly deformed sheared peridotites occur mainly between ∼160 and 185 km depth, firmly within the lithosphere–asthenosphere transition zone. Contrary to many previous models, we suggest that sheared peridotite formation occurs in localized deformation zones spaced out across the entire width of the lithosphere–asthenosphere transition zone, rather than being restricted to a single thin layer at the craton base where mantle flow causes viscous drag. Hence, plate-tectonic stresses acting on the lower cratonic lithosphere may be accommodated by extensive networks of shear zones, which provide transient pathways and sinks for percolating volatile-rich melts, linking the formation of megacrysts and sheared peridotites.