425 research outputs found
Utility of TERT Promoter Mutations for Cutaneous Primary Melanoma Diagnosis
Telomerase reverse transcriptase (TERT) promoter mutations are commonly found in malignant melanomas but rare in melanocytic nevi. To assess its potential diagnostic utility for the distinction of melanoma from nevus, we determined the TERT promoter mutation status of 86 primary melanomas, 72 melanocytic nevi, and 40 diagnostically problematic melanocytic proliferations. Of the 86 melanomas, 67 (77.9%) were TERT-positive, defined as harboring a hotspot TERT promoter mutation at positions -124C>T, -124_125CC>TT, -138_139CC>TT, or -146C>T. Of the 72 nevi, only 1 (1.4%) was TERT-positive. Of the 40 diagnostically uncertain melanocytic proliferations, 2 (5.0%) were TERT-positive. TERT positivity as a test for melanoma versus nevus had an accuracy of 87.3% [95% confidence interval (CI), 81.1-92.1], a sensitivity of 77.9% (95% CI, 68.9-85.4), a specificity of 98.6% (95% CI, 95.8-100), a positive predictive value of 98.5% (95% CI, 95.6-100), and a negative predictive value of 78.9% (95% CI, 72.6-85.4). Our results indicate that hotspot TERT promoter mutation status may be a useful ancillary parameter for the diagnosis of melanoma. In particular, the high specificity of these mutations for melanoma indicates the presence of a TERT promoter mutation in a melanocytic neoplasm associated with diagnostic controversy, or uncertainty should increase concern for a melanoma
Is the Model with the Hopf Term Exactly Equivalent to a Higher Spin Theory?
We write down a local model involving two gauge fields, which is
exactly equivalent to the O(3) model with the Hopf term. We impose the
constraint by using the gaussian representation of the delta function.
For the coefficient of the Hopf term, , 2s being an
integer, we show that the resulting model is exactly equivalent to an
interacting theory of spin- fields. Thus we conjecture that there should be
a fixed point in the spin- theory near which it is exactly equal to the
model.Comment: 11 page
Characterization of the CpG Island Hypermethylated Phenotype Subclass in Primary Melanomas
Cutaneous melanoma can be lethal even if detected at an early stage. Epigenetic profiling may facilitate the identification of aggressive primary melanomas with unfavorable outcomes. We performed clustering of whole-genome methylation data to identify subclasses that were then assessed for survival, clinical features, methylation patterns, and biological pathways. Among 89 cutaneous primary invasive melanomas, we identified three methylation subclasses exhibiting low methylation, intermediate methylation, or hypermethylation of CpG islands, known as the CpG island methylator phenotype (CIMP). CIMP melanomas occurred as early as tumor stage 1b and, compared with low-methylation melanomas, were associated with age at diagnosis ≥65 years, lentigo maligna melanoma histologic subtype, presence of ulceration, higher American Joint Committee on Cancer stage and tumor stage, and lower tumor-infiltrating lymphocyte grade (all P < 0.05). Patients with CIMP melanomas had worse melanoma-specific survival (hazard ratio = 11.84; confidence interval = 4.65‒30.20) than those with low-methylation melanomas, adjusted for age, sex, American Joint Committee on Cancer stage, and tumor-infiltrating lymphocyte grade. Genes hypermethylated in CIMP compared with those in low-methylation melanomas included PTEN, VDR, PD-L1, TET2, and gene sets related to development/differentiation, the extracellular matrix, and immunity. CIMP melanomas exhibited hypermethylation of genes important in melanoma progression and tumor immunity, and although present in some early melanomas, CIMP was associated with worse survival independent of known prognostic factors
Histological assessment of paxgene tissue fixation and stabilization reagents
Within SPIDIA, an EC FP7 project aimed to improve pre analytic procedures, the PAXgene Tissue System (PAXgene), was designed to improve tissue quality for parallel molecular and morphological analysis. Within the SPIDIA project promising results were found in both genomic and proteomic experiments with PAXgene-fixed and paraffin embedded tissue derived biomolecules. But, for this technology to be accepted for use in both clinical and basic research, it is essential that its adequacy for preserving morphology and antigenicity is validated relative to formalin fixation. It is our aim to assess the suitability of PAXgene tissue fixation for (immuno)histological methods. Normal human tissue specimens (n = 70) were collected and divided into equal parts for fixation either with formalin or PAXgene. Sections of the obtained paraffin-embedded tissue were cut and stained. Morphological aspects of PAXgene-fixed tissue were described and also scored relative to formalin-fixed tissue. Performance of PAXgene-fixed tissue in immunohistochemical and in situ hybridization assays was also assessed relative to the corresponding formalin-fixed tissues. Morphology of PAXgene-fixed paraffin embedded tissue was well preserved and deemed adequate for diagnostics in most cases. Some antigens in PAXgene-fixed and paraffin embedded sections were detectable without the need for antigen retrieval, while others were detected using standard, formalin fixation based, immunohistochemistry protocols. Comparable results were obtained with in situ hybridization and histochemical stains. Basically all assessed histological techniques were found to be applicable to PAXgene-fixed and paraffin embedded tissue. In general results obtained with PAXgene-fixed tissue are comparable to those of formalin-fixed tissue. Compromises made in morphology can be called minor compared to the advantages in the molecular pathology possibilities
Shrinking a large dataset to identify variables associated with increased risk of Plasmodium falciparum infection in Western Kenya
Large datasets are often not amenable to analysis using traditional single-step approaches. Here, our general objective was to apply imputation techniques, principal component analysis (PCA), elastic net and generalized linear models to a large dataset in a systematic approach to extract the most meaningful predictors for a health outcome. We extracted predictors for Plasmodium falciparum infection, from a large covariate dataset while facing limited numbers of observations, using data from the People, Animals, and their Zoonoses (PAZ) project to demonstrate these techniques: data collected from 415 homesteads in western Kenya, contained over 1500 variables that describe the health, environment, and social factors of the humans, livestock, and the homesteads in which they reside. The wide, sparse dataset was simplified to 42 predictors of P. falciparum malaria infection and wealth rankings were produced for all homesteads. The 42 predictors make biological sense and are supported by previous studies. This systematic data-mining approach we used would make many large datasets more manageable and informative for decision-making processes and health policy prioritization
Global Search for New Physics with 2.0/fb at CDF
Data collected in Run II of the Fermilab Tevatron are searched for
indications of new electroweak-scale physics. Rather than focusing on
particular new physics scenarios, CDF data are analyzed for discrepancies with
the standard model prediction. A model-independent approach (Vista) considers
gross features of the data, and is sensitive to new large cross-section
physics. Further sensitivity to new physics is provided by two additional
algorithms: a Bump Hunter searches invariant mass distributions for "bumps"
that could indicate resonant production of new particles; and the Sleuth
procedure scans for data excesses at large summed transverse momentum. This
combined global search for new physics in 2.0/fb of ppbar collisions at
sqrt(s)=1.96 TeV reveals no indication of physics beyond the standard model.Comment: 8 pages, 7 figures. Final version which appeared in Physical Review D
Rapid Communication
Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events
The - oscillation frequency has been measured with a sample of
23 million \B\bar B pairs collected with the BABAR detector at the PEP-II
asymmetric B Factory at SLAC. In this sample, we select events in which both B
mesons decay semileptonically and use the charge of the leptons to identify the
flavor of each B meson. A simultaneous fit to the decay time difference
distributions for opposite- and same-sign dilepton events gives ps.Comment: 7 pages, 1 figure, submitted to Physical Review Letter
Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set
We report a measurement of the bottom-strange meson mixing phase \beta_s
using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays
in which the quark-flavor content of the bottom-strange meson is identified at
production. This measurement uses the full data set of proton-antiproton
collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment
at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity.
We report confidence regions in the two-dimensional space of \beta_s and the
B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2,
-1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in
agreement with the standard model expectation. Assuming the standard model
value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +-
0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +-
0.009 (syst) ps, which are consistent and competitive with determinations by
other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012
Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector
A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results
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