High-dose imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: High rates of rapid cytogenetic and molecular responses

Purpose: Long-term clinical outcome data have established imatinib 400 mg/d as standard front-line treatment for newly diagnosed patients with chronic myeloid leukemia (CML). Patients and Methods: The Rationale and Insight for Gleevec High-Dose Therapy (RIGHT) trial is a multicenter study of imatinib 400 mg twice a day as initial therapy in 115 patients (70% Sokal low risk) with newly diagnosed CML in chronic phase who were observed for both molecular and cytogenetic responses for up to 18 months. Eighty-three patients (72%) completed the study, 10 patients (9%) discontinued the study because of adverse events, and six patients (5%) discontinued because of unsatisfactory therapeutic effect. Results: Polymerase chain reaction analysis demonstrated rapid kinetics of major molecular response (MMR), with 48% of patients achieving MMR by 6 months, 54% by 12 months, and 63% by 18 months. Corresponding complete molecular response rates were 39%, 44%, and 55%, respec- tively. Median dose-intensity was 98%. Overall, 79% of patients who received at least 90% dose-intensity achieved MMR. The most frequent adverse events included myelosuppression, rash, fatigue, and musculoskeletal symptoms. Conclusion: This study suggests that imatinib 400 mg twice a day results in more rapid reduction in tumor burden than imatinib 400 mg/d with minimal added toxicit

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

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

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

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