Imputation of truncated p-values for meta-analysis methods and its genomic application

Microarray analysis to monitor expression activities in thousands of genes simultaneously has become routine in biomedical research during the past decade. A tremendous amount of expression profiles are generated and stored in the public domain and information integration by meta-analysis to detect differentially expressed (DE) genes has become popular to obtain increased statistical power and validated findings. Methods that aggregate transformed $p$-value evidence have been widely used in genomic settings, among which Fisher's and Stouffer's methods are the most popular ones. In practice, raw data and $p$-values of DE evidence are often not available in genomic studies that are to be combined. Instead, only the detected DE gene lists under a certain $p$-value threshold (e.g., DE genes with $p$-value${}<0.001$) are reported in journal publications. The truncated $p$-value information makes the aforementioned meta-analysis methods inapplicable and researchers are forced to apply a less efficient vote counting method or na\"{i}vely drop the studies with incomplete information. The purpose of this paper is to develop effective meta-analysis methods for such situations with partially censored $p$-values. We developed and compared three imputation methods - mean imputation, single random imputation and multiple imputation - for a general class of evidence aggregation methods of which Fisher's and Stouffer's methods are special examples. The null distribution of each method was analytically derived and subsequent inference and genomic analysis frameworks were established. Simulations were performed to investigate the type I error, power and the control of false discovery rate (FDR) for (correlated) gene expression data. The proposed methods were applied to several genomic applications in colorectal cancer, pain and liquid association analysis of major depressive disorder (MDD). The results showed that imputation methods outperformed existing na\"{i}ve approaches. Mean imputation and multiple imputation methods performed the best and are recommended for future applications.Comment: Published in at http://dx.doi.org/10.1214/14-AOAS747 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

A mutation in amino acid permease AAP6 reduces the amino acid content of the Arabidopsis sieve elements but leaves aphid herbivores unaffected

The aim of this study was to investigate the role of the amino acid permease gene AAP6 in regulating phloem amino acid composition and then to determine the effects of this altered diet on aphid performance. A genotype of Arabidopsis thaliana (L.) was produced in which the function of the amino acid permease gene AAP6 (At5g49630) was abolished. Plants homozygous for the insertionally inactivated AAP6 gene had a significantly larger mean rosette width than the wild type and a greater number of cauline leaves. Seeds from the aap6 mutant were also significantly larger than those from the wild-type plants. Sieve element (SE) sap was collected by aphid stylectomy and the amino acids derivatized, separated, and quantified using Capillary Electrophoresis with Laser Induced Fluorescence (CE-LIF). In spite of the large variation across samples, the total amino acid concentration of SE sap of the aap6 mutant plants was significantly lower than that of the wild-type plants. The concentrations of lysine, phenylalanine, leucine, and aspartic acid were all significantly lower in concentration in the aap6 mutant plants compared with wild-type plants. This is the first direct demonstration of a physiological role for an amino acid transporter in regulating SE composition in vivo. The amino acid availability in sieve element sap is thought to be the major limiting factor for aphid growth and reproduction. Despite the changes in their diet, the aphid Myzus persicae (Sulzer) displayed only small changes in feeding behaviour on mutant plants when measured using the Electronic Penetration Graph (EPG) technique. Salivation by the aphid into the SE (E1 phase) was increased on mutant plants but there was no significant effect on other feeding EPG behaviours, or in the rate of honeydew production. Consistent with the small effect on aphid feeding behaviour, there was only a small effect of reduced sieve element amino acid concentration on aphid reproduction. The data are discussed in relation to the regulation of phloem composition and the role of phloem amino acids in regulating aphid performance

Randomized trial of conventional transseptal needle versus radiofrequency energy needle puncture for left atrial access (the TRAVERSE-LA study).

BackgroundTransseptal puncture is a critical step in achieving left atrial (LA) access for a variety of cardiac procedures. Although the mechanical Brockenbrough needle has historically been used for this procedure, a needle employing radiofrequency (RF) energy has more recently been approved for clinical use. We sought to investigate the comparative effectiveness of an RF versus conventional needle for transseptal LA access.Methods and resultsIn this prospective, single-blinded, controlled trial, 72 patients were randomized in a 1:1 fashion to an RF versus conventional (BRK-1) transseptal needle. In an intention-to-treat analysis, the primary outcome was time required for transseptal LA access. Secondary outcomes included failure of the assigned needle, visible plastic dilator shavings from needle introduction, and any procedural complication. The median transseptal puncture time was 68% shorter using the RF needle compared with the conventional needle (2.3 minutes [interquartile range {IQR}, 1.7 to 3.8 minutes] versus 7.3 minutes [IQR, 2.7 to 14.1 minutes], P = 0.005). Failure to achieve transseptal LA access with the assigned needle was less common using the RF versus conventional needle (0/36 [0%] versus 10/36 [27.8%], P &lt; 0.001). Plastic shavings were grossly visible after needle advancement through the dilator and sheath in 0 (0%) RF needle cases and 12 (33.3%) conventional needle cases (P &lt; 0.001). There were no differences in procedural complications (1/36 [2.8%] versus 1/36 [2.8%]).ConclusionsUse of an RF needle resulted in shorter time to transseptal LA access, less failure in achieving transseptal LA access, and fewer visible plastic shavings

Saphenous Vein Graft Pseudoaneurysm Treated With Covered Stenting.

Saphenous vein graft (SVG) pseudoaneurysms are an infrequent, but life-threatening complication of coronary artery bypass grafting (CABG) surgery if left untreated. Here, we discuss the case of a 77-year-old patient, with a prior history of CABG and transcatheter aortic valve implantation (TAVI), who was incidentally found on computed tomography angiography (CTA) to have a pseudoaneurysm of his SVG with an initial chief complaint of dizziness. Despite increasing reports of SVG pseudoaneurysm, there is no consensus on definitive treatment. Due to the high mortality risk of this patient with surgical intervention, a minimally invasive percutaneous coronary intervention was performed.&nbsp;The patient was effectively treated with two overlapping Viabahn-covered stents, which completely excluded the pseudoaneurysm. Follow-up imaging at two months showed two well-positioned overlapping self-expanding stents with total occlusion of the pseudoaneurysm

Diameter-Dependent Electron Mobility of InAs Nanowires

Temperature-dependent I-V and C-V spectroscopy of single InAs nanowire field-effect transistors were utilized to directly shed light on the intrinsic electron transport properties as a function of nanowire radius. From C-V characterizations, the densities of thermally-activated fixed charges and trap states on the surface of untreated (i.e., without any surface functionalization) nanowires are investigated while enabling the accurate measurement of the gate oxide capacitance; therefore, leading to the direct assessment of the field-effect mobility for electrons. The field-effect mobility is found to monotonically decrease as the radius is reduced to sub-10 nm, with the low temperature transport data clearly highlighting the drastic impact of the surface roughness scattering on the mobility degradation for miniaturized nanowires. More generally, the approach presented here may serve as a versatile and powerful platform for in-depth characterization of nanoscale, electronic materials

Red supergiant candidates for multimessenger monitoring of the next Galactic supernova

We compile a catalogue of 578 highly probable and 62 likely red supergiants (RSGs) of the Milky Way, which represents the largest list of Galactic RSG candidates designed for continuous follow-up efforts to date. We match distances measured by Gaia DR3, 2MASS photometry, and a 3D Galactic dust map to obtain luminous bright late-type stars. Determining the stars' bolometric luminosities and effective temperatures, we compare to Geneva stellar evolution tracks to determine likely RSG candidates, and quantify contamination using a catalogue of Galactic AGB in the same luminosity-temperature space. We add details for common or interesting characteristics of RSG, such as multistar system membership, variability, and classification as a runaway. As potential future core-collapse supernova progenitors, we study the ability of the catalogue to inform the Supernova Early Warning System (SNEWS) coincidence network made to automate pointing, and show that for 3D position estimates made possible by neutrinos, the number of progenitor candidates can be significantly reduced, improving our ability to observe the progenitor pre-explosion and the early phases of core-collapse supernovae

Red Supergiant Candidates for Multimessenger Monitoring of the Next Galactic Supernova

We compile a catalog of 598 highly probable and 79 likely red supergiants (RSGs) of the Milky Way, which represents the largest list of Galactic RSG candidates to date. We matched distances measured by Gaia DR3, 2MASS photometry, and a 3D Galactic dust map to obtain luminous bright late-type stars. Determining the stars' bolometric luminosities and effective temperatures, we compared to Geneva stellar evolution tracks to determine likely RSG candidates, and quantified contamination using a catalog of Galactic AGB in the same luminosity-temperature space. We add details for common or interesting characteristics of RSG, such as multi-star system membership, variability, and classification as a runaway. As potential future core-collapse supernova (SN) progenitors, we studied the ability of the catalog to inform the Supernova Early Warning System (SNEWS) coincidence network made to automate pointing, and show that for 3D position estimates made possible by neutrinos, the number of progenitor candidates can be significantly reduced, improving our ability to observe the progenitor pre-explosion and the early phases of the core-collapse supernova.Comment: 21 pages, 10 figures, 5 table. Comments welcom

Architecting the Communication and Navigation Networks for NASA's Space Exploration Systems

NASA is planning a series of short and long duration human and robotic missions to explore the Moon and then Mars. A key objective of the missions is to grow, through a series of launches, a system of systems communication, navigation, and timing infrastructure at minimum cost while providing a network-centric infrastructure that maximizes the exploration capabilities and science return. There is a strong need to use architecting processes in the mission pre-formulation stage to describe the systems, interfaces, and interoperability needed to implement multiple space communication systems that are deployed over time, yet support interoperability with each deployment phase and with 20 years of legacy systems. In this paper we present a process for defining the architecture of the communications, navigation, and networks needed to support future space explorers with the best adaptable and evolable network-centric space exploration infrastructure. The process steps presented are: 1) Architecture decomposition, 2) Defining mission systems and their interfaces, 3) Developing the communication, navigation, networking architecture, and 4) Integrating systems, operational and technical views and viewpoints. We demonstrate the process through the architecture development of the communication network for upcoming NASA space exploration missions