Design of a multicast router for network-on-chip architectures with irregular topologies

As chip complexity keeps increasing in system-on-chip (SoC), the on-chip interconnect has become a critical issue for large-scale chip design.It has been proposed that the packet-switched network exchanging messages between intellectual property (IP) cores is a viable solution for the SoC interconnect problem.The design of the router in such network-on-chip (NoC) architectures is the key to high-performance communication for the IP cores in SoC. In this paper, we present the design and implementation of a multicast router for NoC with irregular topologies.The router employs our previously proposed tree-based routing algorithm for irregular networks.Our experiment results show that the multicast router has a slightly lower clock rate and moderately larger chip area than the unicast router in NoC.Since multicasting is a technique providing superior network performance, especially for large networks, such multicast router design is an effective routing solution for large-scale network-on-chip architectures

Retraction: Estimation of progression of multi-state chronic disease using the Markov model and prevalence pool concept

This article [1] has been retracted because the Editors are unable to ensure the scientific veracity of the findings or the ethical conduct of the authors despite an extensive investigation

Assessment of gene-covariate interactions by incorporating covariates into association mapping

The HLA region is considered to be the main genetic risk factor for rheumatoid arthritis. Previous research demonstrated that HLA-DRB1 alleles encoding the shared epitope are specific for disease that is characterized by antibodies to cyclic citrullinated peptides (anti-CCP). In the present study, we incorporated the shared epitope and either anti-CCP antibodies or rheumatoid factor into linkage disequilibrium mapping, to assess the association between the shared epitope or antibodies with the disease gene identified. Incorporating the covariates into the association mapping provides a mechanism 1) to evaluate gene-gene and gene-environment interactions and 2) to dissect the pathways underlying disease induction/progress in quantitative antibodies

A new analysis tool for individual-level allele frequency for genomic studies

<p>Abstract</p> <p>Background</p> <p>Allele frequency is one of the most important population indices and has been broadly applied to genetic/genomic studies. Estimation of allele frequency using genotypes is convenient but may lose data information and be sensitive to genotyping errors.</p> <p>Results</p> <p>This study utilizes a unified intensity-measuring approach to estimating individual-level allele frequencies for 1,104 and 1,270 samples genotyped with the single-nucleotide-polymorphism arrays of the Affymetrix Human Mapping 100K and 500K Sets, respectively. Allele frequencies of all samples are estimated and adjusted by coefficients of preferential amplification/hybridization (CPA), and large ethnicity-specific and cross-ethnicity databases of CPA and allele frequency are established. The results show that using the CPA significantly improves the accuracy of allele frequency estimates; moreover, this paramount factor is insensitive to the time of data acquisition, effect of laboratory site, type of gene chip, and phenotypic status. Based on accurate allele frequency estimates, analytic methods based on individual-level allele frequencies are developed and successfully applied to discover genomic patterns of allele frequencies, detect chromosomal abnormalities, classify sample groups, identify outlier samples, and estimate the purity of tumor samples. The methods are packaged into a new analysis tool, ALOHA (<b>A</b>llele-frequency/<b>L</b>oss-<b>o</b>f-<b>h</b>eterozygosity/<b>A</b>llele-imbalance).</p> <p>Conclusions</p> <p>This is the first time that these important genetic/genomic applications have been simultaneously conducted by the analyses of individual-level allele frequencies estimated by a unified intensity-measuring approach. We expect that additional practical applications for allele frequency analysis will be found. The developed databases and tools provide useful resources for human genome analysis via high-throughput single-nucleotide-polymorphism arrays. The ALOHA software was written in R and R GUI and can be downloaded at <url>http://www.stat.sinica.edu.tw/hsinchou/genetics/aloha/ALOHA.htm</url>.</p

Chinese Herbal Medicine Therapy and the Risk of Mortality for Chronic Hepatitis B Patients with Concurrent Liver Cirrhosis: a Nationwide Population-Based Cohort Study

Chronic hepatitis B (CHB) is increasingly recognized as a public health problem in Taiwan. After affected patients are diagnosed with contaminant liver cirrhosis (LC), adverse clinical outcomes, especially death, are common. This study aimed to investigate the effect of Chinese herbal medicine (CHM), an essential branch of Traditional Chinese medicine (TCM), on the mortality risk among CHB patients with contaminant LC. This longitudinal cohort study used the Taiwanese National Health Insurance Research Database to identify 1522 patients 20–70 years of age with newly diagnosed CHB with LC during 1998–2007. Among them, 508 (33.37%) had received CHM products after the onset of CHB (CHM users), and the remaining 1014 patients (66.63%) were designated as a control group (non-CHM users). All enrollees were followed until the end of 2012 to determine deaths during the study period. We applied the Cox proportional hazards regression model to compute the hazard ratio for the association of CHM use and the subsequent risk of death. During the follow-up period, 156 CHM users and 493 non-CHM users died. After controlling for potential confounders, CHM users were found to have a significantly reduced risk of death compared with non-CHM users by 56%, and the effect was predominantly observed among those treated with CHM for \u3e 180 days. CHM therapy lowered the risk of death among CHB patients with contaminant LC, which supported CHM might provide further treatment options for those with chronic liver diseases

Comparative global immune-related gene profiling of somatic cells, human pluripotent stem cells and their derivatives: implication for human lymphocyte proliferation.

Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), represent potentially unlimited cell sources for clinical applications. Previous studies have suggested that hPSCs may benefit from immune privilege and limited immunogenicity, as reflected by the reduced expression of major histocompatibility complex class-related molecules. Here we investigated the global immune-related gene expression profiles of human ESCs, hiPSCs and somatic cells and identified candidate immune-related genes that may alter their immunogenicity. The expression levels of global immune-related genes were determined by comparing undifferentiated and differentiated stem cells and three types of human somatic cells: dermal papilla cells, ovarian granulosa cells and foreskin fibroblast cells. We identified the differentially expressed genes CD24, GATA3, PROM1, THBS2, LY96, IFIT3, CXCR4, IL1R1, FGFR3, IDO1 and KDR, which overlapped with selected immune-related gene lists. In further analyses, mammalian target of rapamycin complex (mTOR) signaling was investigated in the differentiated stem cells following treatment with rapamycin and lentiviral transduction with specific short-hairpin RNAs. We found that the inhibition of mTOR signal pathways significantly downregulated the immunogenicity of differentiated stem cells. We also tested the immune responses induced in differentiated stem cells by mixed lymphocyte reactions. We found that CD24- and GATA3-deficient differentiated stem cells including neural lineage cells had limited abilities to activate human lymphocytes. By analyzing the transcriptome signature of immune-related genes, we observed a tendency of the hPSCs to differentiate toward an immune cell phenotype. Taken together, these data identify candidate immune-related genes that might constitute valuable targets for clinical applications

Association between use of non–vitamin k oral anticoagulants with and without concurrent medications and risk of major bleeding in nonvalvular atrial fibrillation

Importance:  Non–vitamin K oral anticoagulants (NOACs) are commonly prescribed with other medications that share metabolic pathways that may increase major bleeding risk. Objective:  To assess the association between use of NOACs with and without concurrent medications and risk of major bleeding in patients with nonvalvular atrial fibrillation. Design, Setting, and Participants:  Retrospective cohort study using data from the Taiwan National Health Insurance database and including 91 330 patients with nonvalvular atrial fibrillation who received at least 1 NOAC prescription of dabigatran, rivaroxaban, or apixaban from January 1, 2012, through December 31, 2016, with final follow-up on December 31, 2016. Exposures:  NOAC with or without concurrent use of atorvastatin; digoxin; verapamil; diltiazem; amiodarone; fluconazole; ketoconazole, itraconazole, voriconazole, or posaconazole; cyclosporine; erythromycin or clarithromycin; dronedarone; rifampin; or phenytoin. Main Outcomes and Measures:  Major bleeding, defined as hospitalization or emergency department visit with a primary diagnosis of intracranial hemorrhage or gastrointestinal, urogenital, or other bleeding. Adjusted incidence rate differences between person-quarters (exposure time for each person during each quarter of the calendar year) of NOAC with or without concurrent medications were estimated using Poisson regression and inverse probability of treatment weighting using the propensity score. Results:  Among 91 330 patients with nonvalvular atrial fibrillation (mean age, 74.7 years [SD, 10.8]; men, 55.8%; NOAC exposure: dabigatran, 45 347 patients; rivaroxaban, 54 006 patients; and apixaban, 12 886 patients), 4770 major bleeding events occurred during 447 037 person-quarters with NOAC prescriptions. The most common medications co-prescribed with NOACs over all person-quarters were atorvastatin (27.6%), diltiazem (22.7%), digoxin (22.5%), and amiodarone (21.1%). Concurrent use of amiodarone, fluconazole, rifampin, and phenytoin with NOACs had a significant increase in adjusted incidence rates per 1000 person-years of major bleeding than NOACs alone: 38.09 for NOAC use alone vs 52.04 for amiodarone (difference, 13.94 [99% CI, 9.76-18.13]); 102.77 for NOAC use alone vs 241.92 for fluconazole (difference, 138.46 [99% CI, 80.96-195.97]); 65.66 for NOAC use alone vs 103.14 for rifampin (difference, 36.90 [99% CI, 1.59-72.22); and 56.07 for NOAC use alone vs 108.52 for phenytoin (difference, 52.31 [99% CI, 32.18-72.44]; P &lt; .01 for all comparisons). Compared with NOAC use alone, the adjusted incidence rate for major bleeding was significantly lower for concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin and was not significantly different for concurrent use of verapamil; diltiazem; cyclosporine; ketoconazole, itraconazole, voriconazole, or posaconazole; and dronedarone. Conclusions and Relevance:  Among patients taking NOACs for nonvalvular atrial fibrillation, concurrent use of amiodarone, fluconazole, rifampin, and phenytoin compared with the use of NOACs alone, was associated with increased risk of major bleeding. Physicians prescribing NOAC medications should consider the potential risks associated with concomitant use of other drugs

Bizarre parosteal osteochondromatous proliferation on a phalanx with periosteal erosion

SummaryBizarre parosteal osteochondromatous proliferation (BPOP) is an uncommon benign hand tumor with a high rate of local recurrence, marked proliferative activity, and an atypical histological appearance. The aim of this paper is to present a rare and illustrative example of BPOP with periosteal erosion. A 64-year-old male presented with a 10-year history of a mass, measuring approximately 3 cm in diameter, on the dorsal aspect of the right index finger. On physical examination, the mass was hard, indolent, and located at the level of the proximal phalanx. Roentgenograms displayed a soft tissue mass over the right index finger with erosion of the periosteum. Magnetic resonance imaging revealed a few well-defined lobulated tumors over the right index finger proximal interphalangeal joint with periosteal reaction. The soft tissue tumors were excised and found to have soft consistencies. Pathological findings demonstrated that the tumor was compatible with BPOP. BPOP is a benign but locally aggressive fibro-osseous mass yielding radiographic findings that bear striking clinical similarities to those of other diseases, such as osteochondroma, osteosarcoma, and myositis ossificans. As the radiographic findings of BPOP are equivocal, the differential diagnosis must be based on the pathological results. With this case report, we aim to inform physicians that a hand tumor with an aggressive clinical picture may be benign in origin