Detection of human papillomavirus DNA in formalin-fixed, paraffin-embedded squamous papillomas of the oral cavity

Squamous papillomas are exophytic proliferations of surface oral epithelium. Human papillomavirus (HPV) infection is widely accepted as the etiology of squamous papillomas however the virus cannot be detected in a significant percentage of lesions. Using polymerase chain reaction (PCR), we tested 35 formalin-fixed paraffin-embedded (FFPE) squamous papillomas for the presence of HPV DNA. Six papillomas (17%) tested positive for HPV DNA; four contained HPV-6 and two contained HPV-11. Given that ??globin DNA was only identified in half of the samples, DNA degradation appears to have significantly impacted the results. The results likely represent an underestimation of the true number of HPV-positive specimens in our study. Potential explanations for HPV-negative squamous papillomas include transient HPV infection, failure of the experiment to detect HPV if present, or the possibility that some lesions may not result from HPV infection

Landfill Futures: : National Guideline Document

This report looks at the past and present roles of landfills in Australian waste management and considers the requirements for a sustainable future. The research used a test case to apply an integrated resource planning model to waste. The results suggest that disposal to landfill may be an expensive and less preferred option compared to others, in many cases, but still have a role to play in specific contexts where the costs of other options are higher

Multivisceral intestinal transplantation: Surgical pathology

We report the diagnostic surgical pathology of two children who underwent multivisceral abdominal transplantation and survived for 1 month and 6 months. There is little relevant literature, and diagnostic criteria for the various clinical possibilities are not established; this is made more complicated by the simultaneous occurrence of more than one process. We based our interpretations on conventional histology, augmented with immunohistology, including HLA staining that distinguished graft from host cells in situ. In some instances functional analysis of T cells propagated from the same biopsies was available and was used to corroborate morphological interpretations. A wide spectrum of changes was encountered. Graft-versus-host disease, a prime concern before surgery, was not seen. Rejection was severe in 1 patient, not present in the other, and both had evidence of lymphoproliferative disease, which was related to Epstein-Barr virus. Bacterial translocation through the gut wall was also a feature in both children. This paper documents and illustrates the various diagnostic possibilities.. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Ethanol Pharmacokinetics in Neonates Secondary to Medication Administration

Purpose: Ethanol serves as a solvent and microbial preservative in oral liquid medications and is the second most commonly used solvent in liquid medications following water. Despite widespread use of ethanol in liquid medications for neonates, the pharmacokinetics and toxicity of ethanol in young children are not well described. The aim of the current study is to quantify blood ethanol levels in neonates secondary to oral ethanol containing medications. Methods: Neonates who received either oral phenobarbital (15% ethanol) and/or oral dexamethasone (30% ethanol) per standard of care were eligible for enrollment. A maximum of 6 blood samples per patient (4.5 mL total) were taken over the study period. Blood samples were collected via heel stick at the time of clinical laboratory collections or following a specific collection for study purposes. In addition, blood samples were collected from neonates receiving sublingual buprenorphine (30% ethanol) for neonatal abstinence syndrome from a separate clinical study. Blood ethanol levels were measured using a validated headspace gas chromatography-mass spectrometry method utilizing micro-volume ( ̴100uL) plasma samples. The limit of detection and lower limit of quantification for the assay were 0.1 mg/L and 0.5 mg/L respectively. Results: A total of 39 plasma samples from 15 neonates who were on ethanol containing medications were collected over the study period. Four neonates were exposed to phenobarbital and/or dexamethasone, while eleven neonates were exposed to buprenorphine alone or in combination with phenobarbital. Patients were exposed to an average of 71.6 mg/kg (range 13.1 to 215 mg/kg) of ethanol after a single dose of an ethanol containing medication. Blood ethanol levels were detectable in 98% (38/39) of samples, quantifiable in 67% (26/39) of samples, and ranged from below detection to 85.4 mg/L. Ethanol was rapidly cleared and did not accumulate with current dosing regimens. Conclusion: Ethanol intake secondary to medication administration varied widely. Blood ethanol levels in neonates were low and ethanol was eliminated rapidly after a single dose of oral medications that contained a sizable fraction of ethanol.https://jdc.jefferson.edu/petposters/1000/thumbnail.jp

GENIE: a software package for gene-gene interaction analysis in genetic association studies using multiple GPU or CPU cores

<p>Abstract</p> <p>Background</p> <p>Gene-gene interaction in genetic association studies is computationally intensive when a large number of SNPs are involved. Most of the latest Central Processing Units (CPUs) have multiple cores, whereas Graphics Processing Units (GPUs) also have hundreds of cores and have been recently used to implement faster scientific software. However, currently there are no genetic analysis software packages that allow users to fully utilize the computing power of these multi-core devices for genetic interaction analysis for binary traits.</p> <p>Findings</p> <p>Here we present a novel software package GENIE, which utilizes the power of multiple GPU or CPU processor cores to parallelize the interaction analysis. GENIE reads an entire genetic association study dataset into memory and partitions the dataset into fragments with non-overlapping sets of SNPs. For each fragment, GENIE analyzes: 1) the interaction of SNPs within it in parallel, and 2) the interaction between the SNPs of the current fragment and other fragments in parallel. We tested GENIE on a large-scale candidate gene study on high-density lipoprotein cholesterol. Using an NVIDIA Tesla C1060 graphics card, the GPU mode of GENIE achieves a speedup of 27 times over its single-core CPU mode run.</p> <p>Conclusions</p> <p>GENIE is open-source, economical, user-friendly, and scalable. Since the computing power and memory capacity of graphics cards are increasing rapidly while their cost is going down, we anticipate that GENIE will achieve greater speedups with faster GPU cards. Documentation, source code, and precompiled binaries can be downloaded from <url>http://www.cceb.upenn.edu/~mli/software/GENIE/</url>.</p

Amino acid residues in five separate HLA genes can explain most of the known associations between the MHC and primary biliary cholangitis.

Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disease characterised by progressive destruction of intrahepatic bile ducts. The strongest genetic association is with HLA-DQA1*04:01, but at least three additional independent HLA haplotypes contribute to susceptibility. We used dense single nucleotide polymorphism (SNP) data in 2861 PBC cases and 8514 controls to impute classical HLA alleles and amino acid polymorphisms using state-of-the-art methodologies. We then demonstrated through stepwise regression that association in the HLA region can be largely explained by variation at five separate amino acid positions. Three-dimensional modelling of protein structures and calculation of electrostatic potentials for the implicated HLA alleles/amino acid substitutions demonstrated a correlation between the electrostatic potential of pocket P6 in HLA-DP molecules and the HLA-DPB1 alleles/amino acid substitutions conferring PBC susceptibility/protection, highlighting potential new avenues for future functional investigation

A genome-wide scan for common alleles affecting risk for autism

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C

Discovering joint associations between disease and gene pairs with a novel similarity test

Genes in a functional pathway can have complex interactions. A gene might activate or suppress another gene, so it is of interest to test joint associations of gene pairs. To simultaneously detect the joint association between disease and two genes (or two chromosomal regions), we propose a new test with the use of genomic similarities. Our test is designed to detect epistasis in the absence of main effects, main effects in the absence of epistasis, or the presence of both main effects and epistasis. Results: The simulation results show that our similarity test with the matching measure is more powerful than the Pearson's chi(2) test when the disease mutants were introduced at common haplotypes, but is less powerful when the disease mutants were introduced at rare haplotypes. Our similarity tests with the counting measures are more sensitive to marker informativity and linkage disequilibrium patterns, and thus are often inferior to the similarity test with the matching measure and the Pearson 's chi(2) test. Conclusions: In detecting joint associations between disease and gene pairs, our similarity test is a complementary method to the Pearson's chi(2) test

Consequences of epistasis on growth in an erhualian × white duroc pig cross

Epistasis describes an interaction between the effects of loci. We included epistasis in quantitative trait locus (QTL) mapping of growth at a series of ages in a cross of a Chinese pig breed, Erhualian, with a commercial line, White Duroc. Erhualian pigs have much lower growth rates than White Duroc. We improved a method for genomewide testing of epistasis and present a clear analysis workflow. We also suggest a new approach for interpreting epistasis results where significant additive and dominance effects of a locus in specific backgrounds are determined. In total, seventeen QTL were found and eleven showed epistasis. Loci on chromosomes 2, 3, 4 and 7 were highlighted as affecting growth at more than one age or forming an interaction network. Epistasis resulted in both the QTL on chromosomes 3 and 7 having effects in opposite directions. We believe it is the first time for the chromosome 7 locus that an allele from a Chinese breed has been found to decrease growth. The consequences of epistasis were diverse. Results were impacted by using growth rather than body weight as the phenotype and by correcting for an effect of mother. Epistasis made a considerable contribution to growth in this population and modelling epistasis was important for accurately determining QTL effects