DNA repair biomarkers XPF and phospho-MAPKAP kinase 2 correlate with clinical outcome in advanced head and neck cancer.

BackgroundInduction chemotherapy is a common therapeutic option for patients with locoregionally-advanced head and neck cancer (HNC), but it remains unclear which patients will benefit. In this study, we searched for biomarkers predicting the response of patients with locoregionally-advanced HNC to induction chemotherapy by evaluating the expression pattern of DNA repair proteins.MethodsExpression of a panel of DNA-repair proteins in formalin-fixed paraffin embedded specimens from a cohort of 37 HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation were analyzed using quantitative immunohistochemistry.ResultsWe found that XPF (an ERCC1 binding partner) and phospho-MAPKAP Kinase 2 (pMK2) are novel biomarkers for HNSCC patients undergoing platinum-based induction chemotherapy. Low XPF expression in HNSCC patients is associated with better response to induction chemoradiotherapy, while high XPF expression correlates with a worse response (p = 0.02). Furthermore, low pMK2 expression was found to correlate significantly with overall survival after induction plus chemoradiation therapy (p = 0.01), suggesting that pMK2 may relate to chemoradiation therapy.ConclusionsWe identified XPF and pMK2 as novel DNA-repair biomarkers for locoregionally-advanced HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation. Our study provides insights for the use of DNA repair biomarkers in personalized diagnostics strategies. Further validation in a larger cohort is indicated

The Pediatric Sepsis Biomarker Risk Model (PERSEVERE) Biomarkers Predict Clinical Deterioration and Mortality in Immunocompromised Children Evaluated for Infection

Pediatric sepsis and bacterial infection cause significant morbidity and mortality worldwide, with immunocompromised patients being at particularly high risk of rapid deterioration and death. This study evaluated if PERSEVERE, PERSEVERE-II, or the PERSEVERE biomarkers, can reliably estimate the risk of clinical deterioration and 28-day mortality among immunocompromised pediatric patients. This is a single-center prospective cohort study conducted from July 2016 through September 2017 incorporating 400 episodes of suspected bacterial infection from the inpatient units at Cincinnati Children's Hospital Medical Center, a large, tertiary care children's hospital. The primary analysis assessed clinical deterioration within 72 hours of evaluation for infection. Secondarily, we assessed 28-day mortality. Clinical deterioration was seen in 15% of subjects. Twenty-eight day mortality was 5%, but significantly higher among critically ill patients. Neither PERSEVERE nor PERSEVERE-II performed well to predict clinical deterioration or 28-day mortality, thus we derived new stratification models using the PERSEVERE biomarkers with both high sensitivity and negative predictive value. In conclusion, we evaluated previously validated biomarker risk models in a novel population of largely non-critically ill immunocompromised pediatric patients, and attempted to stratify patients based on a new outcome metric, clinical deterioration. The new highly predictive models indicate common physiologic pathways to clinical deterioration or death from bacterial infection

Annihilation-Gamma-based Diagnostic Techniques for Magnetically Confined Electron-Positron Pair Plasma

Efforts are underway to magnetically confine electron--positron pair plasmas to study their unique behavior, which is characterized by significant changes in plasma time and length scales, supported waves, and unstable modes. However, use of conventional plasma diagnostics presents challenges with these low-density and annihilating matter-antimatter plasma. To address this problem, we propose to develop techniques based on the distinct emission provided by annihilation. This emission exhibits two spatial correlations: the distance attenuation of isotropic sources and the back-to-back propagation of momentum-preserving 2-$\gamma$ annihilation. We present the results of our analysis of the $\gamma$ emission rate and the spatial profile of the annihilation in a magnetized pair plasma from direct pair collisions, from the formation and decay of positronium, as well as from transport processes. In order to demonstrate the effectiveness of annihilation-based techniques, we tested them on annular $\gamma$ emission profiles produced by a $\beta^+$ radioisotope on a rotating turntable. Direct and positronium-mediated annihilation result in overlapping volumetric $\gamma$ sources, and the 2-$\gamma$ emission from these volumetric sources can be tomographically reconstructed from coincident counts in multiple detectors. Transport processes result in localized annihilation where field lines intersect walls, limiters, or internal magnets. These localized sources can be identified by the fractional $\gamma$ counts on spatially distributed detectors.Comment: 21 pages, 11 figures, 2 tables, contribution to the 13th International Workshop on Non-Neutral Plasma

Injection of Positrons into a Dense Electron Cloud in a Magnetic Dipole Trap

The creation of an electron space charge in a dipole magnetic trap and the subsequent injection of positrons has been experimentally demonstrated. Positrons (5eV) were magnetically guided from their source and injected into the trapping field generated by a permanent magnet (0.6T at the poles) using a cross field E $\times$ B drift, requiring tailored electrostatic and magnetic fields. The electron cloud is created by thermionic emission from a tungsten filament. The maximum space charge potential of the electron cloud reaches -42V, which is consistent with an average electron density of ($4 \pm 2$) $\times 10^{12}$ $\text{m}^{-3}$ and a Debye length of ($2 \pm 1$) $\text{cm}$. We demonstrate that the presence of this space potential does not hamper efficient positron injection. Understanding the effects of the negative space charge on the injection and confinement of positrons represents an important intermediate step towards the production of a confined electron-positron pair plasma

Improved study of a possible Theta+ production in the pp -> p K0 sigma+ reaction with the COSY-TOF spectrometer

The pp -> p K0 Sigma+ reaction was investigated with the TOF spectrometer at COSY at 3.059 GeV/c incident beam momentum. The main objective was to clarify whether or not a narrow exotic S = +1 resnance, the Theta+ pentaquark, is populated at 1.53 GeV/c2 in the K0 p subsystem with a data sample of much higher statistical significance compared to the previously reported data in this channel. An analysis of these data does not confirm the existence of the Theta+ pentaquark. This is expressed as an upper limit for the cross section sigma (pp -> p K0 Sigma+) < 0.15 microbarn at the 95 percent confidence level.Comment: 11 pages, 5 figure

A High Statistics Measurement of the Lambdac+ Lifetime

A high statistics measurement of the Lambdac+ lifetime from the Fermilab fixed-target FOCUS photoproduction experiment is presented. We describe the analysis technique with particular attention to the determination of the systematic uncertainty. The measured value of 204.6 +/- 3.4 (stat.) +/- 2.5 (syst.) fs from 8034 +/- 122 Lambdac -> pKpi decays represents a significant improvement over the present world average.Comment: Submitted to Physical Review Letter

Identification of cancer predisposition variants in apparently healthy individuals using a next-generation sequencing-based family genomics approach

Cancer, like many common disorders, has a complex etiology, often with a strong genetic component and with multiple environmental factors contributing to susceptibility. A considerable number of genomic variants have been previously reported to be causative of, or associated with, an increased risk for various types of cancer. Here, we adopted a next-generation sequencing approach in 11 members of two families of Greek descent to identify all genomic variants with the potential to predispose family members to cancer. Cross-comparison with data from the Human Gene Mutation Database identified a total of 571 variants, from which 47 % were disease-associated polymorphisms, 26 % disease-associated polymorphisms with additional supporting functional evidence, 19 % functional polymorphisms with in vitro/laboratory or in vivo supporting evidence but no known disease association, 4 % putative disease-causing mutations but with some residual doubt as to their pathological significance, and 3 % disease-causing mutations. Subsequent analysis, focused on the latter variant class most likely to be involved in cancer predisposition, revealed two variants of prime interest, namely MSH2 c.2732T>A (p.L911R) and BRCA1 c.2955delC, the first of which is novel. KMT2D c.13895delC and c.1940C>A variants are additionally reported as incidental findings. The next-generation sequencing-based family genomics approach described herein has the potential to be applied to other types of complex genetic disorder in order to identify variants of potential pathological significance

A Measurement of the Ds+ Lifetime

A high statistics measurement of the Ds+ lifetime from the Fermilab fixed-target FOCUS photoproduction experiment is presented. We describe the analysis of the two decay modes, Ds+ -> phi(1020)pi+ and Ds+ -> \bar{K}*(892)0K+, used for the measurement. The measured lifetime is 507.4 +/- 5.5 (stat.) +/- 5.1 (syst.) fs using 8961 +/- 105 Ds+ -> phi(1020)pi+ and 4680 +/- 90 Ds+ -> \bar{K}*(892)0K+ decays. This is a significant improvement over the present world average.Comment: 5 pages, 3 figures, 2 tables, submitted to PR

Dalitz Plot Analysis of the Decay D^+ --> K^- pi^+ pi^+ and Indication of a Low-Mass Scalar K pi Resonance

We study the Dalitz plot of the decay D^+ --> K^- pi^+ pi^+ with a sample of 15090 events from Fermilab experiment E791. Modeling the decay amplitude as the coherent sum of known K pi resonances and a uniform nonresonant term, we do not obtain an acceptable fit. If we allow the mass and width of the K^*_0(1430) to float, we obtain values consistent with those from PDG but the chi^2 per degree of freedom of the fit is still unsatisfactory. A good fit is found when we allow for the presence of an additional scalar resonance, with mass 797 +/- 19 +/- 43 MeV/c^2 and width 410 +/- 43 +/- 87 MeV/c^2. The mass and width of the K^*_0(1430) become 1459 +/- 7 +/- 5 MeV/c^2 and 175 +/- 12 +/- 12 MeV/c^2, respectively. Our results provide new information on the scalar sector in hadron spectroscopy.Comment: Accepted for publication in Physical Review Letter