6,392 research outputs found
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- annihilation. We present the results of our
analysis of the 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 emission profiles produced by a
radioisotope on a rotating turntable. Direct and positronium-mediated
annihilation result in overlapping volumetric sources, and the
2- 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 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 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 ()
and a Debye length of () .
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
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