Characterisation of nanovoiding in dental porcelain using small angle neutron scattering and transmission electron microscopy

Objectives Recent studies of the yttria partially stabilised zirconia–porcelain interface have revealed the presence of near-interface porcelain nanovoiding which reduces toughness and leads to component failure. One potential explanation for these nanoscale features is thermal creep which is induced by the combination of the residual stresses at the interface and sintering temperatures applied during manufacture. The present study provides improved understanding of this important phenomenon. Methods Transmission electron microscopy and small angle neutron scattering were applied to a sample which was crept at 750 °C and 100 MPa (sample C), a second which was exposed to an identical heat treatment schedule in the absence of applied stress (sample H), and a reference sample in the as-machined state (sample A). Results The complementary insights provided by the two techniques were in good agreement and log-normal void size distributions were found in all samples. The void number density was found to be 1.61 μm−2, 25.4 μm−2 and 98.6 μm−2 in samples A, H and C respectively. The average void diameter in sample A (27.1 nm) was found to be more than twice as large as in samples H (10.2 nm) and C (11.6 nm). The crept data showed the highest skewness parameter (2.35), indicating stress-induced growth of larger voids and void coalescence that has not been previously observed. Significance The improved insight presented in this study can be integrated into existing models of dental prostheses in order to optimise manufacturing routes and thereby reduce the significant detrimental impact of this nanostructural phenomenon.</p

Computational analysis of expression of human embryonic stem cell-associated signatures in tumors

<p>Abstract</p> <p>Background</p> <p>The cancer stem cell model has been proposed based on the linkage between human embryonic stem cells and human cancer cells. However, the evidences supporting the cancer stem cell model remain to be collected. In this study, we extensively examined the expression of human embryonic stem cell-associated signatures including core genes, transcription factors, pathways and microRNAs in various cancers using the computational biology approach.</p> <p>Results</p> <p>We used the class comparison analysis and survival analysis algorithms to identify differentially expressed genes and their associated transcription factors, pathways and microRNAs among normal vs. tumor or good prognosis vs. poor prognosis phenotypes classes based on numerous human cancer gene expression data. We found that most of the human embryonic stem cell- associated signatures were frequently identified in the analysis, suggesting a strong linkage between human embryonic stem cells and cancer cells.</p> <p>Conclusions</p> <p>The present study revealed the close linkage between the human embryonic stem cell associated gene expression profiles and cancer-associated gene expression profiles, and therefore offered an indirect support for the cancer stem cell theory. However, many interest issues remain to be addressed further.</p

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

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InVeST proceedings, 10-12 April 2017

“Immersive” technology conveys the sense that participants are being immersed in a task or setting as they would if it were the real world. The benefits of immersive simulation are well documented in human medicine, and a robust industry producing a range of high fidelity human patient simulators (HPS) has resulted. HPS can be programmed to progress through a series of states determined by learner interventions, providing a realistic clinical environment in which trainees can explore treatment options, receive direct feedback from the HPS, and learn from mistakes in a safe environment. There are no comparable simulators on the veterinary market, and HPS are extremely expensive. To supply in this need a robust, expandable veterinary clinical simulation platform using Open Source software and off-the-shelf hardware was developed. This will be made available at no cost to the veterinary education community. The current design is a canine simulator with palpable pulses, auscultable heart and lung sounds and chest movements to mimic spontaneous respiration and sensors to detect positive pressure breaths and chest compressions. A patient monitor (ECG and end-tidal CO2 waveforms, and pulse oximetry, blood pressure and temperature displays) is provided to the learner. The instructor interface is accessible on any computer or mobile device and allows on-the-fly alterations in patient state and management of pre-programmed clinical scenarios. A companion web site will allow sharing of scenarios and extensions to the base functionality through an open source community, affording access to this powerful pedagogical approach to clinical training to a much broader audience than previously possible.Poster presented at the 5th International Veterinary Simulation in Teaching Conference, 10-12 April 2017, held at the Intundla Conference Venue, Pretoria, South Africa.Sponsored by Virtalis, South Africa. Dept. of Higher Education & Training, Anatomoulds, Veterinary Simulator Industries, National Research Foundation, University of Pretoria. Faculty of Veterinary Science, Zoetis and Breed 'n BetsyPoster sponsored by USDA, The State University of New York and Triad Foundationab201

Maternal Azithromycin therapy for Ureaplasma parvum intra-amniotic infection improves fetal hemodynamics in a non-human primate model

BACKGROUND: Ureaplasma parvum infection is a prevalent cause of intrauterine infection associated with preterm birth, preterm premature rupture of membranes, fetal inflammatory response syndrome, and adverse postnatal sequelae. Elucidation of diagnostic and treatment strategies for infection-associated preterm labor may improve perinatal and long-term outcomes for these cases. OBJECTIVE: This study assessed the effect of intraamniotic Ureaplasma infection on fetal hemodynamic and cardiac function and the effect of maternal antibiotic treatment on these outcomes. STUDY DESIGN: Chronically catheterized pregnant rhesus monkeys were assigned to control (n=6), intraamniotic inoculation with Ureaplasma parvum (107 colony-forming units/mL, n=15), and intraamniotic infection plus azithromycin treatment (12.5 mg/kg twice a day intravenously, n=8) groups. At approximately 135 days' gestation (term=165 days), pulsed and color Doppler ultrasonography was used to obtain measurements of fetal hemodynamics (pulsatility index of umbilical artery, ductus venosus, descending aorta, ductus arteriosus, aortic isthmus, right pulmonary artery, middle cerebral artery and cerebroplacental ratio, and left and right ventricular cardiac outputs) and cardiac function (ratio of peak early vs late transmitral flow velocity [marker of ventricular function], Tei index [myocardial performance index]). These indices were stratified by amniotic fluid proinflammatory mediator levels and cardiac histology. RESULTS: Umbilical and fetal pulmonary artery vascular impedances were significantly increased in animals from the intraamniotic inoculation with Ureaplasma parvum group (P1.1) than in those with normal blood flow (P1.6, P CONCLUSION: Fetal hemodynamic alterations were associated with intraamniotic Ureaplasma infection and ameliorated after maternal antibiotic treatment. Doppler ultrasonographic measurements merit continuing investigation as a diagnostic method to identify fetal cardiovascular and hemodynamic compromise associated with intrauterine infection or inflammation and in the evaluation of therapeutic interventions or clinical management of preterm labor.Peer reviewe