Immigrated urn models - asymptotic properties and applications

Urn models have been widely studied and applied in both scientific and social science disciplines. In clinical studies, the adoption of urn models in treatment allocation schemes has been proved to be beneficial to both researchers, by providing more efficient clinical trials, and patients, by increasing the likelihood of receiving the better treatment. In this paper, we propose a new and general class of immigrated urn (IMU) models that incorporates the immigration mechanism into the urn process. Theoretical properties are developed and the advantages of the IMU models are discussed. In general, the IMU models have smaller variabilities than the classical urn models, yielding more powerful statistical inferences in applications. Illustrative examples are presented to demonstrate the wide applicability of the IMU models. The proposed IMU framework, including many popular classical urn models, not only offers a unify perspective for us to comprehend the urn process, but also enables us to generate several novel urn models with desirable properties

Long Span DNA Paired-End-Tag (DNA-PET) Sequencing Strategy for the Interrogation of Genomic Structural Mutations and Fusion-Point-Guided Reconstruction of Amplicons

10.1371/journal.pone.0046152PLoS ONE79

Identification of a Functional Genetic Variant at 16q12.1 for Breast Cancer Risk: Results from the Asia Breast Cancer Consortium

Genetic factors play an important role in the etiology of breast cancer. We carried out a multi-stage genome-wide association (GWA) study in over 28,000 cases and controls recruited from 12 studies conducted in Asian and European American women to identify genetic susceptibility loci for breast cancer. After analyzing 684,457 SNPs in 2,073 cases and 2,084 controls in Chinese women, we evaluated 53 SNPs for fast-track replication in an independent set of 4,425 cases and 1,915 controls of Chinese origin. Four replicated SNPs were further investigated in an independent set of 6,173 cases and 6,340 controls from seven other studies conducted in Asian women. SNP rs4784227 was consistently associated with breast cancer risk across all studies with adjusted odds ratios (95% confidence intervals) of 1.25 (1.20−1.31) per allele (P = 3.2×10−25) in the pooled analysis of samples from all Asian samples. This SNP was also associated with breast cancer risk among European Americans (per allele OR  = 1.19, 95% CI  = 1.09−1.31, P = 1.3×10−4, 2,797 cases and 2,662 controls). SNP rs4784227 is located at 16q12.1, a region identified previously for breast cancer risk among Europeans. The association of this SNP with breast cancer risk remained highly statistically significant in Asians after adjusting for previously-reported SNPs in this region. In vitro experiments using both luciferase reporter and electrophoretic mobility shift assays demonstrated functional significance of this SNP. These results provide strong evidence implicating rs4784227 as a functional causal variant for breast cancer in the locus 16q12.1 and demonstrate the utility of conducting genetic association studies in populations with different genetic architectures

Genome-Wide Association Study in East Asians Identifies Novel Susceptibility Loci for Breast Cancer

Genetic factors play an important role in the etiology of both sporadic and familial breast cancer. We aimed to discover novel genetic susceptibility loci for breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF-β activated kinase (TAB2) gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, with a P-value of 3.8×10−12 in the combined analysis of all samples. Adjusted odds ratios (95% confidence intervals) were 0.89 (0.85–0.94) and 0.80 (0.75–0.86) for the A/G and A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (P = 1.9×10−6 from the combined analysis of all samples), located in intron 5 of the ESR1 gene, and SNP rs7107217 (P = 4.6×10−7), located at 11q24.3, also showed a consistent association in each of the four stages. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the TAB2 gene (6q25.1), and identifies two possible susceptibility loci located in the ESR1 gene and 11q24.3, respectively

Replication and Functional Genomic Analyses of the Breast Cancer Susceptibility Locus at 6q25.1 Generalize Its Importance in Women of Chinese, Japanese, and European Ancestry

We evaluated the generalizability of a single nucleotide polymorphism (SNP), rs2046210 (A/G allele), associated with breast cancer risk that was initially identified at 6q25.1 in a genome-wide association study conducted among Chinese women. In a pooled analysis of over 31,000 women of East-Asian, European, and African ancestry, we found a positive association for rs2046210 and breast cancer risk in Chinese women [ORs (95%CI)=1.30(1.22–1.38) and 1.64(1.50–1.80) for the AG and AA genotypes, respectively, P for trend = 1.54 × 10−30], Japanese women [ORs (95%CI)=1.31(1.13–1.52) and 1.37(1.06–1.76), P for trend = 2.51 × 10−4], and European-ancestry American women [ORs (95%CI)=1.07(0.99–1.16) and 1.18(1.04–1.34), P for trend = 0.0069]. No association with this SNP, however, was observed in African American women [ORs (95%CI)=0.81(0.63–1.06) and 0.85(0.65–1.11) for the AG and AA genotypes, respectively, P for trend = 0.4027). In vitro functional genomic studies identified a putative functional variant, rs6913578. This SNP is 1,440 bp downstream of rs2046210 and is in high LD with rs2046210 in Chinese (r2=0.91) and European-ancestry (r2=0.83) populations, but not in Africans (r2=0.57). SNP rs6913578 was found to be associated with breast cancer risk in Chinese and European-ancestry American women. After adjusting for rs2046210, the association of rs6913578 with breast cancer risk in African Americans approached borderline significance. Results from this large consortium study confirmed the association of rs2046210 with breast cancer risk among women of Chinese, Japanese, and European ancestry. This association may be explained in part by a putatively functional variant (rs6913578) identified in the region

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

An acoustic micromixer using low-powered voice coil actuation

A low-powered acoustic micromixer has been presented in this paper. This newly invented system consists of an open-top mixing chamber and a permanent magnet mixer base. A voice coil is attached to the bottom of the mixing chamber with a polydimethylsiloxane membrane. The optimal driving frequency of each mixing test can be co-determined during (or prior to) the mixing via an electrical impedance (Ze) measurement owing to inherent electro-acoustic coupling of the system. When the mixer is driving at its resonance frequency found from the Ze, mixing efficiency is maximized characterizing millie-watt efficiency to achieve a mixing time scale comparable to other acoustic mixers. In addition, the present mixer demonstrates feasibility of a portable microfluidic system, wherein the degree of mixing may be tracked by Ze monitoring from a smart-phone, which may allow each experiment to be controlled remotely over existing network environment. We believe that our study demonstrates a feasible application of microelectromechanical systems technology for the Internet of Things.ASTAR (Agency for Sci., Tech. and Research, S’pore)MOE (Min. of Education, S’pore

Genetically engineered antibodies targeting human liver cancer cells

This study involves the genetic engineering of a monoclonal antibody mAb-95 and the construction of a single chain fragment (scFv) antibody molecule (scFv95), both of which target human hepatocellular carcinoma (HCC). The mAb-95 was raised with crude membrane fragments of a human liver cancer cell line. Its specificity was confirmed by solid phase ELISA analysis, indirect immunostaining and immuno-gold labeling assays. To construct the scFv95, variable regions of Immunoglobulin (IgG) genes of mAb-95 were inserted into a bacterial expression vector, then expressed and characterized. The scFv95 was shown to have a binding ability to HCC cells. Mutagenesis experiments indicated that complimentary determining region 3 (CDR3) was important in binding to HCC. In particular, position 99 in CDR3 of the heavy chain was found to be crucial for scFv95's ability to bind to HCC. All results indicate that mAb-95 itself and the genetically engineered scFv95 could potentially be used as targeting agents for HCC immunotherapy or immuno-detection