Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

Vertical profiling of aerosol particles and trace gases over the central Arctic Ocean during summer

Unique measurements of vertical size-resolved aerosol particle concentrations, trace gas concentrations and meteorological data were obtained during the Arctic Summer Cloud Ocean Study (ASCOS, www.ascos.se), an International Polar Year project aimed at establishing the processes responsible for formation and evolution of low-level clouds over the high Arctic summer pack ice. The experiment was conducted from on board the Swedish icebreaker Oden, and provided both ship-and helicopter-based measurements. This study focuses on the vertical helicopter profiles and onboard measurements obtained during a three-week period when Oden was anchored to a drifting ice floe, and sheds light on the characteristics of Arctic aerosol particles and their distribution throughout the lower atmosphere. Distinct differences in aerosol particle characteristics within defined atmospheric layers are identified. Within the lowermost couple hundred metres, transport from the marginal ice zone (MIZ), condensational growth and cloud processing develop the aerosol population. During two of the four representative periods defined in this study, such influence is shown. At altitudes above about 1 km, long-range transport occurs frequently. However, only infrequently does large-scale subsidence descend such air masses to become entrained into the mixed layer in the high Arctic, and there-fore long-range transport plumes are unlikely to directly influence low-level stratiform cloud formation. Nonetheless, such plumes can influence the radiative balance of the planetary boundary layer (PBL) by influencing formation and evolution of higher clouds, as well as through precipitation transport of particles downwards. New particle formation was occasionally observed, particularly in the near-surface layer. We hypothesize that the origin of these ultrafine particles could be in biological processes, both primary and secondary, within the open leads between the pack ice and/or along the MIZ. In general, local sources, in combination with upstream boundary-layer transport of precursor gases from the MIZ, are considered to constitute the origin of cloud condensation nuclei (CCN) particles and thus be of importance for the formation of interior Arctic low-level clouds during summer, and subsequently, through cloud influences, for the melting and freezing of sea ice

Two-dimensional high spatial-resolution dosimeter using europium doped potassium chloride: a feasibility study

Recent research has shown that KCl:Eu(2+) has great potential for use in megavoltage radiation therapy dosimetry because this material exhibits excellent storage performance and is reusable due to strong radiation hardness. This work reports the authors’ attempts to fabricate 2D KCl:Eu(2+) storage phosphor films (SPFs) using both a physical vapor deposition (PVD) method and a tape casting method. X ray diffraction analysis showed that a 10 µm thick PVD sample was composed of highly crystalline KCl. No additional phases were observed, suggesting that the europium activator had completed been incorporated into the KCl matrix. Photostimulated luminescence and photoluminescence spectra suggested that F (Cl(-)) centers were the electron storage centers post×ray irradiation and that Eu(2+) cations acted as luminescence centers in the photostimulation process. The 150-µm thick casted KCl:Eu(2+) SPF showed sub-millimeter spatial resolution. Monte Carlo simulations further demonstrated that the admixture of 20% KCl:Eu(2+) and 80% low Z polymer binder exhibited almost no energy dependence in a 6 MV beam. KCl:Eu(2+) pellet samples showed a large dynamic range from 0.01 cGy to 60 Gy dose-to-water, and saturated at approximately 500 Gy as a result of KCl’s intrinsic high radiation hardness. Taken together, this work provides strong evidence that KCl:Eu(2+) based SPF with associated readout apparatus could result in a novel electronic film system that has all the desirable features associated with classic radiographic film and, importantly, water equivalence and the capability of permanent identification of each detector