Content Validity of Anatomic Site-Specific Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Item Sets for Assessment of Acute Symptomatic Toxicities in Radiation Oncology

Purpose: To improve assessment of symptomatic toxicity in cancer clinical trials and complement clinician-based toxicity reporting, the US National Cancer Institute developed a measurement system called the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). The objective of this study was to examine the content validity of PRO-CTCAE in patients undergoing radiation therapy and to establish anatomic site-specific item sets for implementation in cancer research. Methods and Materials: Patients receiving radiation to the brain, head and neck, breast, thorax, abdomen, or pelvis were recruited during the final week of radiation. Participants described side effects qualitatively and completed anatomic site-specific checklists indicating the presence or absence of symptomatic toxicities drawn from the PRO-CTCAE library. Items endorsed by ≥20% of participants were selected for inclusion. Symptomatic toxicities described qualitatively were content analyzed and summarized. Symptomatic toxicities not reflected in the PRO-CTCAE item library were tabulated. Results: We conducted 389 interviews of patients receiving radiation to the brain (n = 46), head and neck (n = 69), breast (n = 134), thorax (n = 30), abdomen (n = 27), female pelvis (n = 36), or male pelvis (n = 47). Median age was 62 years; 62% were female. The 53 solicited PRO-CTCAE symptoms reflected all reported radiation-induced toxicities with the exception of phlegm/mucus production and mouth/throat pain with swallowing in patients receiving head and neck radiation, eye dryness/irritation in patients undergoing brain radiation, and obstructive urinary symptoms in men receiving pelvic radiation. The PRO-CTCAE items “skin burns” and “pain” require greater specificity to adequately reflect toxicities experienced during radiation. Conclusions: PRO-CTCAE demonstrates strong content validity as a measure of symptomatic toxicities in patients receiving radiation. These results provide empirical support for the definition of site-specific PRO-CTCAE item sets to assess the symptomatic toxicities of radiation therapy. The site-specific PRO-CTCAE item sets developed herein are currently being deployed in our department via an electronic platform to capture treatment-related toxicity

An Equation of State of a Carbon-Fibre Epoxy Composite under Shock Loading

An anisotropic equation of state (EOS) is proposed for the accurate extrapolation of high-pressure shock Hugoniot (anisotropic and isotropic) states to other thermodynamic (anisotropic and isotropic) states for a shocked carbon-fibre epoxy composite (CFC) of any symmetry. The proposed EOS, using a generalised decomposition of a stress tensor [Int. J. Plasticity \textbf{24}, 140 (2008)], represents a mathematical and physical generalisation of the Mie-Gr\"{u}neisen EOS for isotropic material and reduces to this equation in the limit of isotropy. Although a linear relation between the generalised anisotropic bulk shock velocity $U^{A}_{s}$ and particle velocity $u_{p}$ was adequate in the through-thickness orientation, damage softening process produces discontinuities both in value and slope in the $U^{A}_{s}$-$u_{p}$ relation. Therefore, the two-wave structure (non-linear anisotropic and isotropic elastic waves) that accompanies damage softening process was proposed for describing CFC behaviour under shock loading. The linear relationship $U^{A}_{s}$-$u_{p}$ over the range of measurements corresponding to non-linear anisotropic elastic wave shows a value of $c^{A}_{0}$ (the intercept of the $U^{A}_{s}$-$u_{p}$ curve) that is in the range between first and second generalised anisotropic bulk speed of sound [Eur. Phys. J. B \textbf{64}, 159 (2008)]. An analytical calculation showed that Hugoniot Stress Levels (HELs) in different directions for a CFC composite subject to the two-wave structure (non-linear anisotropic elastic and isotropic elastic waves) agree with experimental measurements at low and at high shock intensities. The results are presented, discussed and future studies are outlined.Comment: 12 pages, 9 figure

Estimates of hadron azimuthal anisotropy from multiparton interactions in proton-proton collisions at sqrt(s) = 14 TeV

We estimate the amount of collective "elliptic flow" expected at mid-rapidity in proton-proton (p-p) collisions at the CERN Large Hadron Collider (LHC), assuming that any possible azimuthal anisotropy of the produced hadrons with respect to the plane of the reaction follows the same overlap-eccentricity and particle-density scalings as found in high-energy heavy ion collisions. Using a Glauber eikonal model, we compute the p-p eccentricities, transverse areas and particle-multiplicities for various phenomenological parametrisations of the proton spatial density. For realistic proton transverse profiles, we find integrated elliptic flow v2 parameters below 3% in p-p collisions at sqrt(s) = 14 TeV.Comment: 17 pages, 9 figures. Very minor mods. Version to appear in EPJ-

Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial.

IMPORTANCE: Glioblastoma is the most devastating primary malignancy of the central nervous system in adults. Most patients die within 1 to 2 years of diagnosis. Tumor-treating fields (TTFields) are a locoregionally delivered antimitotic treatment that interferes with cell division and organelle assembly. OBJECTIVE: To evaluate the efficacy and safety of TTFields used in combination with temozolomide maintenance treatment after chemoradiation therapy for patients with glioblastoma. DESIGN, SETTING, AND PARTICIPANTS: After completion of chemoradiotherapy, patients with glioblastoma were randomized (2:1) to receive maintenance treatment with either TTFields plus temozolomide (n = 466) or temozolomide alone (n = 229) (median time from diagnosis to randomization, 3.8 months in both groups). The study enrolled 695 of the planned 700 patients between July 2009 and November 2014 at 83 centers in the United States, Canada, Europe, Israel, and South Korea. The trial was terminated based on the results of this planned interim analysis. INTERVENTIONS: Treatment with TTFields was delivered continuously (>18 hours/day) via 4 transducer arrays placed on the shaved scalp and connected to a portable medical device. Temozolomide (150-200 mg/m2/d) was given for 5 days of each 28-day cycle. MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival in the intent-to-treat population (significance threshold of .01) with overall survival in the per-protocol population (n = 280) as a powered secondary end point (significance threshold of .006). This prespecified interim analysis was to be conducted on the first 315 patients after at least 18 months of follow-up. RESULTS: The interim analysis included 210 patients randomized to TTFields plus temozolomide and 105 randomized to temozolomide alone, and was conducted at a median follow-up of 38 months (range, 18-60 months). Median progression-free survival in the intent-to-treat population was 7.1 months (95% CI, 5.9-8.2 months) in the TTFields plus temozolomide group and 4.0 months (95% CI, 3.3-5.2 months) in the temozolomide alone group (hazard ratio [HR], 0.62 [98.7% CI, 0.43-0.89]; P = .001). Median overall survival in the per-protocol population was 20.5 months (95% CI, 16.7-25.0 months) in the TTFields plus temozolomide group (n = 196) and 15.6 months (95% CI, 13.3-19.1 months) in the temozolomide alone group (n = 84) (HR, 0.64 [99.4% CI, 0.42-0.98]; P = .004). CONCLUSIONS AND RELEVANCE: In this interim analysis of 315 patients with glioblastoma who had completed standard chemoradiation therapy, adding TTFields to maintenance temozolomide chemotherapy significantly prolonged progression-free and overall survival. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00916409

The Random Quadratic Assignment Problem

Optimal assignment of classes to classrooms \cite{dickey}, design of DNA microarrays \cite{carvalho}, cross species gene analysis \cite{kolar}, creation of hospital layouts cite{elshafei}, and assignment of components to locations on circuit boards \cite{steinberg} are a few of the many problems which have been formulated as a quadratic assignment problem (QAP). Originally formulated in 1957, the QAP is one of the most difficult of all combinatorial optimization problems. Here, we use statistical mechanical methods to study the asymptotic behavior of problems in which the entries of at least one of the two matrices that specify the problem are chosen from a random distribution $P$. Surprisingly, this case has not been studied before using statistical methods despite the fact that the QAP was first proposed over 50 years ago \cite{Koopmans}. We find simple forms for $C_{\rm min}$ and $C_{\rm max}$, the costs of the minimal and maximum solutions respectively. Notable features of our results are the symmetry of the results for $C_{\rm min}$ and $C_{\rm max}$ and the dependence on $P$ only through its mean and standard deviation, independent of the details of $P$. After the asymptotic cost is determined for a given QAP problem, one can straightforwardly calculate the asymptotic cost of a QAP problem specified with a different random distribution $P$

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

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio