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

Epitaxial growth of deposited amorphous layer by laser annealing

We demonstrate that a single short pulse of laser irradiation of appropriate energy is capable of recrystallizing in open air an amorphous Si layer deposited on a (100) single-crystal substrate into an epitaxial layer. The laser pulse annealing technique is shown to overcome the interfacial oxide obstacle which usually leads to polycrystalline formation in normal thermal annealing

Translational Invariance and the Anisotropy of the Cosmic Microwave Background

Primordial quantum fluctuations produced by inflation are conventionally assumed to be statistically homogeneous, a consequence of translational invariance. In this paper we quantify the potentially observable effects of a small violation of translational invariance during inflation, as characterized by the presence of a preferred point, line, or plane. We explore the imprint such a violation would leave on the cosmic microwave background anisotropy, and provide explicit formulas for the expected amplitudes $$ of the spherical-harmonic coefficients.Comment: Notation improve

Complete and safe resection of challenging retroperitoneal tumors: anticipation of multi-organ and major vascular resection and use of adjunct procedures.

BackgroundRetroperitoneal tumors are often massive and can involve adjacent organs and/or vital structures, making them difficult to resect. Completeness of resection is within the surgeon's control and critical for long-term survival, particularly for malignant disease. Few studies directly address strategies for complete and safe resection of challenging retroperitoneal tumors.MethodsFifty-six patients representing 63 cases of primary or recurrent retroperitoneal tumor resection between 2004-2009 were identified and a retrospective chart review was performed. Rates of complete resection, use of adjunct procedures, and perioperative complications were recorded.ResultsIn 95% of cases, complete resection was achieved. Fifty-eight percent of these cases required en bloc multi-organ resection, and 8% required major vascular resection. Complete resection rates were higher for primary versus recurrent disease. Adjunct procedures (ureteral stents, femoral nerve monitoring, posterior laminotomy, etc.) were used in 54% of cases. Major postoperative complications occurred in 16% of cases, and one patient died (2% mortality).ConclusionsComplete resection of challenging retroperitoneal tumors is feasible and can be done safely with important pre- and intraoperative considerations in mind

Network Topology of an Experimental Futures Exchange

Many systems of different nature exhibit scale free behaviors. Economic systems with power law distribution in the wealth is one of the examples. To better understand the working behind the complexity, we undertook an empirical study measuring the interactions between market participants. A Web server was setup to administer the exchange of futures contracts whose liquidation prices were coupled to event outcomes. After free registration, participants started trading to compete for the money prizes upon maturity of the futures contracts at the end of the experiment. The evolving `cash' flow network was reconstructed from the transactions between players. We show that the network topology is hierarchical, disassortative and scale-free with a power law exponent of 1.02+-0.09 in the degree distribution. The small-world property emerged early in the experiment while the number of participants was still small. We also show power law distributions of the net incomes and inter-transaction time intervals. Big winners and losers are associated with high degree, high betweenness centrality, low clustering coefficient and low degree-correlation. We identify communities in the network as groups of the like-minded. The distribution of the community sizes is shown to be power-law distributed with an exponent of 1.19+-0.16.Comment: 6 pages, 12 figure

Clinical impact of double protease inhibitor boosting with Lopinavir/Ritonavir and Amprenavir as part of salvage antiretroviral therapy

Purpose: Double protease inhibitor (PI) boosting is being explored as a new strategy in salvage antiretroviral (ARV) therapy. However, if a negative drug interaction leads to decreased drug levels of either or both PIs, double PI boosting could lead to decreased virologic response. A negative drug interaction has been described between amprenavir (APV) and lopinavir/ritonavir (LPV/r). This observational cohort study assessed the virologic impact of the addition of APV to a salvage ARV regimen, which also contains LPV/r, compared to a regimen containing LPV/r alone. Method: Patients initiated on a salvage ARV regimen that included LPV/r obtained from the expanded access program in Toronto, Canada, were evaluated. APV (600-1,200 mg bid) was added at the discretion of the treating physician. Results: Using multivariate Cox proportional hazards models, we found that the addition of APV to a LPV/r-containing salvage regimen was not significantly associated with time to virologic suppression (< 50 copies/mL; adjusted hazard ratio [HR] = 0.75, p = .12) or with time to virologic rebound (adjusted HR = 1.46, p = .34). Those patients who received higher doses of APV had an increased chance of virologic suppression (p = .03). In a subset of 27 patients, the median LPV Ctrough was significantly lower in patients receiving APV (p = .04), and the median APV Ctrough was reduced compared to reported controls. Conclusion: Our data do not support an additional benefit in virologic reduction of double boosting with APV and LPV/r relative to LPV/r alone in salvage ARV therapy. Our study's limitations include its retrospective nature and the imbalance between the two groups potentially confounding the results. Although these factors were adjusted for in the multivariate analysis, a prospective randomized controlled trial is warranted to confirm our findings