The role of molecular biomarkers in recurrent glioblastoma trials:an assessment of the current trial landscape of genome-driven oncology

For glioblastoma patients, the efficacy-targeted therapy is limited to date. Most of the molecular therapies previously studied are lacking efficacy in this population. More trials are needed to study the actual actionability of biomarkers in (recurrent) glioblastoma. This study aimed to assess the current clinical trial landscape to assess the role of molecular biomarkers in trials on recurrent glioblastoma treatment. The database ClinicalTrials.gov was used to identify not yet completed clinical trials on recurrent glioblastoma in adults. Recruiting studies were assessed to investigate the role of molecular criteria, which were retrieved as detailed as possible. Primary outcome was molecular criteria used as selection criteria for study participation. Next to this, details on moment and method of testing, and targets and drugs studied, were collected. In 76% (181/237) of the included studies, molecular criteria were not included in the study design. Of the remaining 56 studies, at least one specific genomic alteration as selection criterium for study participation was required in 33 (59%) studies. Alterations in EGFR, CDKN2A/B or C, CDK4/6, and RB were most frequently investigated, as were the corresponding drugs abemaciclib and ribociclib. Of the immunotherapies, CAR-T therapies were the most frequently studied therapies. Previously, genomics studies have revealed the presence of potentially actionable alterations in glioblastoma. Our study shows that the potential efficacy of targeted treatment is currently not translated into genome-driven trials in patients with recurrent glioblastoma. An intensification of genome-driven trials might help in providing evidence for (in)efficacy of targeted treatments.</p

Health-related quality-of-life results from the randomised phase II TAVAREC trial on temozolomide with or without bevacizumab in 1p/19q intact first-recurrence World Health Organization grade 2 and 3 glioma (European Organization for Research and Treatment of Cancer 26091)

Background: In an international randomised controlled phase II study of temozolomide (TMZ) versus TMZ in combination with bevacizumab (BEV) in locally diagnosed non-1p/19q co-deleted World Health Organization grade 2 or 3 gliomas with a first and contrast-enhancing recurrence after initial radiotherapy, and overall survival at 12 months was not significantly different (61% in the TMZ arm and 55% in the TMZ + BEV arm). Objectives: Health-related quality of life (HRQoL) was a key secondary end-point in this trial, and the main objective of this study was to determine the impact of the addition of BEV to TMZ on HRQoL. Methods: HRQoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 (version 3) and QLQ-BN20 at baseline, and then every 12 weeks until disease progression. The pre-selected primary HRQoL end-point was the QLQ-C30 global health scale, with self-perceived cognitive functioning and pain selected as secondary HRQoL issues. Analysis was undertaken using linear mixed modelling and complemented with sensitivity analyses using summary statistics. A difference was considered clinically relevant with ≥10 points difference on a 100-point scale. Results: Baseline compliance was high at 94% and remained above 60% until 72 weeks, limiting the analysis to 60 weeks. Compliance was similar in both arms. We found no statistically significant or clinically significant differences between the primary HRQoL end-point in both treatment arms (p = 0.2642). The sensitivity analyses confirmed this finding. The overall test for post-baseline differences between the two treatment arms also showed no statistically or clinically significant differences regarding the selected secondary end-point scales. Interpretation: The addition of BEV to TMZ in this patient group neither improves nor negatively impacts HRQoL.</p

Search for strong gravity in multijet final states produced in pp collisions at √s=13 TeV using the ATLAS detector at the LHC

A search is conducted for new physics in multijet final states using 3.6 inverse femtobarns of data from proton-proton collisions at √s = 13TeV taken at the CERN Large Hadron Collider with the ATLAS detector. Events are selected containing at least three jets with scalar sum of jet transverse momenta (HT) greater than 1TeV. No excess is seen at large HT and limits are presented on new physics: models which produce final states containing at least three jets and having cross sections larger than 1.6 fb with HT > 5.8 TeV are excluded. Limits are also given in terms of new physics models of strong gravity that hypothesize additional space-time dimensions

Operation and performance of the ATLAS semiconductor tracker

The semiconductor tracker is a silicon microstrip detector forming part of the inner tracking system of the ATLAS experiment at the LHC. The operation and performance of the semiconductor tracker during the first years of LHC running are described. More than 99% of the detector modules were operational during this period, with an average intrinsic hit efficiency of (99.74±0.04)%. The evolution of the noise occupancy is discussed, and measurements of the Lorentz angle, δ-ray production and energy loss presented. The alignment of the detector is found to be stable at the few-micron level over long periods of time. Radiation damage measurements, which include the evolution of detector leakage currents, are found to be consistent with predictions and are used in the verification of radiation background simulations

The performance of the jet trigger for the ATLAS detector during 2011 data taking

The performance of the jet trigger for the ATLAS detector at the LHC during the 2011 data taking period is described. During 2011 the LHC provided proton–proton collisions with a centre-of-mass energy of 7 TeV and heavy ion collisions with a 2.76 TeV per nucleon–nucleon collision energy. The ATLAS trigger is a three level system designed to reduce the rate of events from the 40 MHz nominal maximum bunch crossing rate to the approximate 400 Hz which can be written to offline storage. The ATLAS jet trigger is the primary means for the online selection of events containing jets. Events are accepted by the trigger if they contain one or more jets above some transverse energy threshold. During 2011 data taking the jet trigger was fully efficient for jets with transverse energy above 25 GeV for triggers seeded randomly at Level 1. For triggers which require a jet to be identified at each of the three trigger levels, full efficiency is reached for offline jets with transverse energy above 60 GeV. Jets reconstructed in the final trigger level and corresponding to offline jets with transverse energy greater than 60 GeV, are reconstructed with a resolution in transverse energy with respect to offline jets, of better than 4 % in the central region and better than 2.5 % in the forward direction

Search for vectorlike B quarks in events with one isolated lepton, missing transverse momentum, and jets at √s = 8 TeV with the ATLAS detector

A search has been performed for pair production of heavy vectorlike down-type (B) quarks. The analysis explores the lepton-plus-jets final state, characterized by events with one isolated charged lepton (electron or muon), significant missing transverse momentum, and multiple jets. One or more jets are required to be tagged as arising from b quarks, and at least one pair of jets must be tagged as arising from the hadronic decay of an electroweak boson. The analysis uses the full data sample of pp collisions recorded in 2012 by the ATLAS detector at the LHC, operating at a center-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 20.3 fb −1 . No significant excess of events is observed above the expected background. Limits are set on vectorlike B production, as a function of the B branching ratios, assuming the allowable decay modes are B → Wt/Zb/Hb. In the chiral limit with a branching ratio of 100% for the decay B → Wt, the observed (expected) 95% C.L. lower limit on the vectorlike B mass is 810 GeV (760 GeV). In the case where the vectorlike B quark has branching ratio values corresponding to those of an SU(2) singlet state, the observed (expected) 95% C.L. lower limit on the vectorlike B mass is 640 GeV (505 GeV). The same analysis, when used to investigate pair production of a colored, charge 5/3 exotic fermion T 5/3 , with subsequent decay T 5/3 → Wt, sets an observed (expected) 95% C.L. lower limit on the T 5/3 mass of 840 GeV (780 GeV)

Measurement of jet charge in dijet events from √s = 8 TeV pp collisions with the ATLAS detector

The momentum-weighted sum of the charges of tracks associated to a jet is sensitive to the charge of the initiating quark or gluon. This paper presents a measurement of the distribution of momentum-weighted sums, called jet charge, in dijet events using 20.3 fb−¹ of data recorded with the ATLAS detector at √s = 8 TeV in pp collisions at the LHC. The jet charge distribution is unfolded to remove distortions from detector effects and the resulting particle-level distribution is compared with several models. The pT dependence of the jet charge distribution average and standard deviation are compared to predictions obtained with several leading-order and next-to-leading-order parton distribution functions. The data are also compared to different Monte Carlo simulations of QCD dijet production using various settings of the free parameters within these models. The chosen value of the strong coupling constant used to calculate gluon radiation is found to have a significant impact on the predicted jet charge. There is evidence for a pT dependence of the jet charge distribution for a given jet flavor. In agreement with perturbative QCD predictions, the data show that the average jet charge of quark-initiated jets decreases in magnitude as the energy of the jet increases

ATLAS Run 1 searches for direct pair production of third-generation squarks at the Large Hadron Collider

This paper reviews and extends searches for the direct pair production of the scalar supersymmetric partners of the top and bottom quarks in proton–proton collisions collected by the ATLAS collaboration during the LHC Run 1. Most of the analyses use 20 fb−1 of collisions at a centre-of-mass energy of s√=8 TeV, although in some case an additional 4.7 fb−1 of collision data at s√=7 TeV are used. New analyses are introduced to improve the sensitivity to specific regions of the model parameter space. Since no evidence of third-generation squarks is found, exclusion limits are derived by combining several analyses and are presented in both a simplified model framework, assuming simple decay chains, as well as within the context of more elaborate phenomenological supersymmetric models.An erratum to this article can be found at http://dx.doi.org/10.1140/epjc/s10052-016-3935-

Promoting Research Activities and Management Reform in Universities : An Approach from Policy Sciences

Many commentators have insisted without empirical evidence that the heterogeneity of fuculty members promotes the research activities in universities. We have to examine whether or not this assertion would be valid and which element of heterogeneity may contribute to promoting research outputs. This article investigates the relationship between heterogeneity in educational background and research performance, then examines how the Science Research Grant has been allocated to faculties in economics. The result shows that the more heterogeneous faculty members are, the more the research outputs increase. The analysis also indicates that the research performance has been little considered in making decision for adoption while it has made significant effect on the amount of grant for the adopted subject