Nonpromoter methylation of the CDKN2A gene with active transcription is associated with improved locoregional control in laryngeal squamous cell carcinoma

We previously reported a novel association between CDKN2A nonpromoter methylation and transcription (ARF/INK4a) in human papillomavirus associated oropharyngeal tumors. In this study we assessed whether nonpromoter CDKN2A methylation in laryngeal squamous cell carcinomas (LXSCC) conferred a similar association with transcription that predicted patient outcome. We compared DNA methylation and ARF/INK4a RNA expression levels for the CDKN2A locus using the Illumina HumanMethylation27 beadchip and RT-PCR in 43 LXSCC tumor samples collected from a prospective study of head and neck cancer patients treated at Montefiore Medical Center (MMC). Validation was performed using RNAseq data on 111 LXSCC tumor samples from the Cancer Genome Atlas (TCGA). The clinical relevance of combined nonpromoter CDKN2A methylation and transcription was assessed by multivariate Cox regression for locoregional recurrence on a subset of 69 LXSCC patients with complete clinicopathologic data from the MMC and TCGA cohorts. We found evidence of CDKN2A nonpromoter hypermethylation in a third of LXSCC from our MMC cohort, which was significantly associated with increased ARF and INK4a RNA expression (Wilcoxon rank-sum, P = 0.007 and 0.003, respectively). A similar association was confirmed in TCGA samples (Wilcoxon rank-sum test P < 0.0001 for ARF and INK4a). Patients with CDKN2A hypermethylation or high ARF/INK4a expression were significantly less likely to develop a locoregional recurrence compared to those with neither of the features, independent of other clinicopatholgic risk factors (adjusted hazard ratio=0.21, 95% confidence interval:0.05-0.81). These results support the conclusion that CDKN2A nonpromoter methylation is associated with increased ARF and INK4a RNA expression, and improved locoregional control in LXSCC

On being a memory expert witness: Three cases

I describe three legal cases in which I acted as a memory expert witness. The cases contain remarkable accounts of memories. Such memories are by no means unusual in legal cases, are often over retention intervals measured in decades, and contain details the specificity of which is highly unusual. For example, recalling from childhood verbatim conversations, clothes worn by self and others, the weather, actions that at the time could not have been understood, details that could not have been known, precise durations and calendar dates, and much more. I show how our scientific understanding of memory can help courts reach more informed decisions about such fantastical "memories" and how these memories constitute data that as researchers we should seek to understand

Rapidity and energy dependence of the electric charge correlations in A+A collisions at the SPS energies

Results from electric charge correlations studied with the Balance Function method in A+A collisions from 20\emph{A} to 158\emph{A} GeV are presented in two different rapidity intervals: In the mid-rapidity region we observe a decrease of the width of the Balance Function distribution with increasing centrality of the collision, whereas this effect vanishes in the forward rapidity region. Results from the energy dependence study in central Pb+Pb collisions show that the narrowing of the Balance Function expressed by the normalised width parameter \textit{W} increases with energy towards the highest SPS and RHIC energies. Finally we compare our experimental data points with predictions of several models. The hadronic string models UrQMD and HIJING do not reproduce the observed narrowing of the Balance Function. However, AMPT which contains a quark-parton transport phase before hadronization can reproduce the narrowing of the BF's width with centrality. This confirms the proposed sensitivity of the Balance Function analysis to the time of hadronization.Comment: Submitted in Phys. Rev.

Electric charge fluctuations in central Pb+Pb collisions at 20, 30, 40, 80 and 158 AGeV

Results are presented on event-by-event electric charge fluctuations in central Pb+Pb collisions at 20, 30, 40, 80 and 158 AGeV. The observed fluctuations are close to those expected for a gas of pions correlated by global charge conservation only. These fluctuations are considerably larger than those calculated for an ideal gas of deconfined quarks and gluons. The present measurements do not necessarily exclude reduced fluctuations from a quark-gluon plasma because these might be masked by contributions from resonance decays.Comment: 19 pages, 8 figure

Bose-Einstein correlations of pion pairs in central Pb+Pb collisions at CERN SPS energies

Measurements of Bose-Einstein correlations of pion pairs in central Pb+Pb collisions were performed with the NA49 detector at the CERN SPS for beam energies of 20A, 30A, 40A, 80A, and 158A GeV. Correlation functions were measured in the longitudinally co-moving ``out-side-long'' reference frame as a function of rapidity and transverse momentum in the forward hemisphere of the reaction. Radius and correlation strength parameters were obtained from fits of a Gaussian parametrization. The results show a decrease of the radius parameters with increasing transverse momentum characteristic of strong radial flow in the pion source. No striking dependence on pion-pair rapidity or beam energy is observed. Static and dynamic properties of the pion source are obtained from simultaneous fits with a blast-wave model to radius parameters and midrapidity transverse momentum spectra. Predictions of hydrodynamic and microscopic models of Pb+Pb collisions are discussed.Comment: 22 pages, 23 figure

Upper Limit of D0 Production in Central Pb-Pb Collisions at 158A GeV

Results are presented from a search for the decays D0 -> Kmin piplus and D0bar -> Kplus pimin in a sample of 3.8x10^6 central Pb-Pb events collected with a beam energy of 158A GeV by NA49 at the CERN SPS. No signal is observed. An upper limit on D0 production is derived and compared to predictions from several models.Comment: REVTEX 5 pages, 4 figure

Pion and kaon production in central Pb+Pb collisions at 20A and 30A GeV: Evidence for the onset of deconfinement

Results on charged pion and kaon production in central Pb+Pb collisions at 20A and 30A GeV are presented and compared to data at lower and higher energies. A rapid change of the energy dependence is observed around 30A GeV for the yields of pions and kaons as well as for the shape of the transverse mass spectra. The change is compatible with the prediction that the threshold for production of a state of deconfined matter at the early stage of the collisions is located at low SPS energies.Comment: 12 pages, 8 figure

Parton coalescence at RHIC

Using a covariant coalescence model, we study hadron production in relativistic heavy ion collisions from both soft partons in the quark-gluon plasma and hard partons in minijets. Including transverse flow of soft partons and independent fragmentation of minijet partons, the model is able to describe available experimental data on pion, kaon, and antiproton spectra. The resulting antiproton to pion ratio is seen to increase at low transverse momenta and reaches a value of about one at intermediate transverse momenta, as observed in experimental data at RHIC. A similar dependence of the antikaon to pion ratio on transverse momentum is obtained, but it reaches a smaller value at intermediate transverse momenta. At high transverse momenta, the model predicts that both the antiproton to pion and the antikaon to pion ratio decrease and approach those given by the perturbative QCD. Both collective flow effect and coalescence of minijet partons with partons in the quark-gluon plasma affect significantly the spectra of hadrons with intermediate transverse momenta. Elliptic flows of protons, Lambdas, and Omegas have also been evaluated from partons with elliptic flows extracted from fitting measured pion and kaon elliptic flows, and they are found to be consistent with available experimental data.Comment: 12 pages, 11 figure

Energy Dependence of Multiplicity Fluctuations in Heavy Ion Collisions at the CERN SPS

Multiplicity fluctuations of positively, negatively and all charged hadrons in the forward hemisphere were studied in central Pb+Pb collisions at 20A, 30A, 40A, 80A and 158A GeV. The multiplicity distributions and their scaled variances are presented in dependence of collision energy as well as of rapidity and transverse momentum. The distributions have bell-like shape and their scaled variances are in the range from 0.8 to 1.2 without any significant structure in their energy dependence. No indication of the critical point in fluctuations are observed. The string-hadronic model UrQMD significantly overpredicts the mean, but approximately reproduces the scaled variance of the multiplicity distributions. The predictions of the statistical hadron-resonance gas model obtained within the grand-canonical and canonical ensembles disagree with the measured scaled variances. The narrower than Poissonian multiplicity fluctuations measured in numerous cases may be explained by the impact of conservation laws on fluctuations in relativistic systems.Comment: 26 pages, 34 figures, updated version including referee comment