Genetically Determined Height and Risk of Non-hodgkin Lymphoma

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00\u20131.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01\u20131.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes

The type II-plateau supernova 2017eaw in NGC 6946 and its red supergiant progenitor

We present extensive optical photometric and spectroscopic observations, from 4 to 482 days after explosion, of the Type II-plateau (II-P) supernova (SN) 2017eaw in NGC 6946. SN 2017eaw is a normal SN II-P intermediate in properties between, for example, SN 1999em and SN 2012aw and the more luminous SN 2004et, also in NGC 6946. We have determined that the extinction to SN 2017eaw is primarily due to the Galactic foreground and that the SN site metallicity is likely subsolar. We have also independently confirmed a tip-of-the-red-giant-branch (TRGB) distance to NGC 6946 of 7.73 ± 0.78 Mpc. The distances to the SN that we have also estimated via both the standardized candle method and expanding photosphere method corroborate the TRGB distance. We confirm the SN progenitor identity in pre-explosion archival Hubble Space Telescope (HST) and Spitzer Space Telescope images, via imaging of the SN through our HST Target of Opportunity program. Detailed modeling of the progenitor's spectral energy distribution indicates that the star was a dusty, luminous red supergiant consistent with an initial mass of ~15 M ⊙

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer's disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer's disease and other tau-mediated neurodegenerative diseases

Inflammatory biomarkers in Alzheimer's disease plasma

Introduction: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a \u201cHoly Grail\u201d of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APO\u3b54 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation

Final Moments II: Observational Properties and Physical Modeling of CSM-Interacting Type II Supernovae

International audienceWe present ultraviolet/optical/near-infrared observations and modeling of Type II supernovae (SNe II) whose early-time ($\delta t < 2$ days) spectra show transient, narrow emission lines from shock ionization of confined ($r < 10^{15}$ cm) circumstellar material (CSM). The observed electron-scattering broadened line profiles (i.e., IIn-like) of HI, He I/II, C III/IV, and N III/IV/V from the CSM persist on a characteristic timescale ($t_{\rm IIn}$) that marks a transition to a lower-density CSM and the emergence of Doppler-broadened features from the fast-moving SN ejecta. Our sample, the largest to date, consists of 39 SNe with early-time IIn-like features in addition to 35 "comparison" SNe with no evidence of early-time IIn-like features, all with ultraviolet observations. The total sample consists of 50 unpublished objects with 474 previously unpublished spectra and 50 multiband light curves, collected primarily through the Young Supernova Experiment and Global Supernova Project collaborations. For all sample objects, we find a significant correlation between peak ultraviolet brightness and both $t_{\rm IIn}$ and the rise time, as well as evidence for enhanced peak luminosities in SNe II with IIn-like features. We quantify mass-loss rates and CSM density for the sample through matching of peak multiband absolute magnitudes, rise times, $t_{\rm IIn}$ and optical SN spectra with a grid of radiation hydrodynamics and non-local thermodynamic equilibrium (nLTE) radiative-transfer simulations. For our grid of models, all with the same underlying explosion, there is a trend between the duration of the electron-scattering broadened line profiles and inferred mass-loss rate: $t_{\rm IIn} \approx 3.8[\dot{M}/(0.01 \textrm{M}_{\odot} \textrm{yr}^{-1})]$ days

Actively personalized vaccination trial for newly diagnosed glioblastoma

Experimentele farmacotherapi