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Showing papers by "Fred R. Hirsch published in 2010"


Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, A. A. Abdelalim4  +3232 moreInstitutions (192)
TL;DR: A search for new heavy particles manifested as resonances in two-jet final states in 7 TeV proton-proton collisions by the LHC is presented, extending the reach of previous experiments.
Abstract: A search for new heavy particles manifested as resonances in two-jet final states is presented. The data were produced in 7 TeV proton-proton collisions by the LHC and correspond to an integrated luminosity of 315 nb(-1) collected by the ATLAS detector. No resonances were observed. Upper limits were set on the product of cross section and signal acceptance for excited-quark (q*) production as a function of q* mass. These exclude at the 95% C. L. the q* mass interval 0: 30< m(q)*< 1:26 TeV, extending the reach of previous experiments.

137 citations


Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, A. A. Abdelalim4  +3240 moreInstitutions (194)
TL;DR: In this paper, the first measurements of the W and Z/gamma*-boson production cross sections in proton-proton collisions at 7 TeV are presented using data recorded by the ATLAS experiment at the LHC.
Abstract: First measurements of the W -> lnu and Z/gamma* -> ll (l = e, mu) production cross sections in proton-proton collisions at sqrt(s) = 7 TeV are presented using data recorded by the ATLAS experiment at the LHC. The results are based on 2250 W -> lnu and 179 Z/gamma* -> ll candidate events selected from a data set corresponding to an integrated luminosity of approximately 320 nb-1. The measured total W and Z/gamma*-boson production cross sections times the respective leptonic branching ratios for the combined electron and muon channels are $\stotW$ * BR(W -> lnu) = 9.96 +- 0.23(stat) +- 0.50(syst) +- 1.10(lumi) nb and $\stotZg$ * BR(Z/gamma* -> ll) = 0.82 +- 0.06(stat) +- 0.05(syst) +- 0.09(lumi) nb (within the invariant mass window 66 < m_ll < 116 GeV). The W/Z cross-section ratio is measured to be 11.7 +- 0.9(stat) +- 0.4(syst). In addition, measurements of the W+ and W- production cross sections and of the lepton charge asymmetry are reported. Theoretical predictions based on NNLO QCD calculations are found to agree with the measurements.

131 citations


Journal ArticleDOI
TL;DR: IGF1R protein and gene expression does not associate with survival, whereas high IGF1R gene copy number harbors positive prognostic value, which was confirmed in multivariate analysis.
Abstract: Purpose The purpose of this study was to characterize insulin-like growth factor-1 receptor (IGF1R) protein expression, mRNA expression, and gene copy number in surgically resected non–small-cell lung cancers (NSCLC) in relation to epidermal growth factor receptor (EGFR) protein expression, patient characteristics, and prognosis. Patients and Methods One hundred eighty-nine patients with NSCLC who underwent curative pulmonary resection were studied (median follow-up, 5.3 years). IGF1R protein expression was evaluated by immunohistochemistry (IHC) with two anti-IGF1R antibodies (n 179). EGFR protein expression was assessed with PharmDx kit. IGF1R gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) from 114 corresponding fresh-frozen samples. IGF1R gene copy number was assessed by fluorescent in situ hybridization using customized probes (n 181).

122 citations


Journal ArticleDOI
TL;DR: The mutation-specific IHC antibodies have high sensitivity and specificity for predefined EFGR mutations and may be suitable for screening for these predefined mutations, however, negative IHC results require further mutation analyses before excluding EGFR-targeted therapy.

118 citations


Journal ArticleDOI
Georges Aad1, Georges Aad2, E. Abat3, Brad Abbott4  +3253 moreInstitutions (185)
TL;DR: In this paper, the performance of the ATLAS detector in the first half a million minimum bias events of the LHC collision data was investigated at center-of-mass energies of 0.9 TeV and 2.36 TeV.
Abstract: More than half a million minimum-bias events of LHC collision data were collected by the ATLAS experiment in December 2009 at centre-of-mass energies of 0.9 TeV and 2.36 TeV. This paper reports on studies of the initial performance of the ATLAS detector from these data. Comparisons between data and Monte Carlo predictions are shown for distributions of several track- and calorimeter-based quantities. The good performance of the ATLAS detector in these first data gives confidence for successful running at higher energies.

78 citations


Journal ArticleDOI
TL;DR: Although both regimens met the efficacy criterion for continued evaluation, the concurrent regimen of paclitaxel/carboplatin plus cetuximab was chosen.
Abstract: Purpose Randomized clinical trials failed to show a survival benefit for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors plus concurrent chemotherapy in patients with metastatic non–small-cell lung cancer (NSCLC), with preclinical data suggesting potential negative interactions. In contrast, pilot trials of the EGFR-targeted antibody, cetuximab, plus chemotherapy suggested enhanced antitumor activity. This randomized phase II trial was designed to select a cetuximab plus chemotherapy regimen for phase III evaluation. Patients and Methods Treatment-naive patients with advanced-stage NSCLC were randomly assigned to receive paclitaxel (225 mg/m2) and carboplatin (area under the curve, 6) every 3 weeks plus concurrent cetuximab (400 mg/m2 loading dose followed by 250 mg/m2 weekly) for four cycles followed by maintenance cetuximab or sequential paclitaxel-carboplatin for four cycles followed by cetuximab. Results Of 242 patients enrolled, 224 were eligible and assessable for response (106 an...

67 citations


Journal ArticleDOI
TL;DR: SCLC is characterized by frequent high-IGF1R protein expression, increased gene copy number, and occasional occurrence of true gene amplification, which may have important implications for future anti-IGf1R therapeutic approaches.

52 citations


Journal ArticleDOI
TL;DR: The apparent promise of CA-FISH in sputum for assessing lung cancer risk and/or for lung cancer early detection now needs to be validated in a clinical screening trial.
Abstract: Lung cancer usually is disseminated (advanced) and has a poor prognosis at diagnosis. Current and former smokers are at a high risk for lung cancer and are candidates for prevention and early detection strategies. Sputum is a potential source of biomarkers that might determine either lung cancer risk or the presence of early lung cancer, but no current sputum test is sufficiently sensitive and specific for effective screening. We used fluorescence in situ hybridization (FISH) to measure chromosomal aneusomy (CA) in sputum samples collected prospectively from 100 incident lung cancer cases and 96 controls (matched on age, gender, and date of collection) nested within an ongoing high-risk cohort. The CA-FISH assay was aimed at four DNA targets: epidermal growth factor receptor, MYC, 5p15, and CEP 6. The sensitivity of a positive CA-FISH assay (abnormal for two or more of the four markers) for lung cancer was substantially higher for samples collected within 18 months (76% sensitivity) than for samples collected more than 18 months (31%) before lung cancer diagnosis. Sensitivity was higher for squamous cell cancers (94%) than for other histologic types (69%). CA-FISH specificity based on samples collected within 18 months before diagnosis was 88%. The adjusted odds ratio (OR) of lung cancer for specimens collected within 18 months before a cancer diagnosis was higher for the CA-FISH assay [OR, 29.9; 95% confidence interval (95% CI), 9.5-94.1] than for previously studied ORs of cytologic atypia (OR, 1.8; 95% CI, 1.3-2.6) and gene promoter methylation (OR, 6.5; 95% CI, 1.2-35.5). Whether CA-FISH is an indicator of extreme risk for incident lung cancer or detects exfoliated cancer cells is unknown. The apparent promise of CA-FISH in sputum for assessing lung cancer risk and/or for lung cancer early detection now needs to be validated in a clinical screening trial.

47 citations


Journal ArticleDOI
TL;DR: The rationale and issues related to early lung cancer screening, the management of screen-detected primary cancers and different approaches that have been tested for screening are described.
Abstract: Accounting for 28% of all cancer deaths and causing 1.3 million deaths worldwide every year, lung cancer is the most lethal cancer. Diagnosing and treating cancer at its early stages, ideally during precancerous stages, could increase the 5-year survival rate by three- to four-fold with a potential for cure. Thus far, no screening method has been shown to decrease disease-specific mortality rate. The present review describes the rationale and issues related to early lung cancer screening, the management of screen-detected primary cancers and different approaches that have been tested for screening. These include imaging techniques, bronchoscopies, molecular screenings from different noninvasive or invasive sources, such as blood, sputum, bronchoscopic samples and exhaled breath.

40 citations


Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, A. A. Abdelalim4  +2853 moreInstitutions (180)
TL;DR: In this article, the ionization signals in the liquid argon of the ATLAS electromagnetic calorimeter are studied in detail using cosmic muons, and the drift time of the ionisation electrons is measured and used to assess the intrinsic uniformity of the CALorimeter gaps and estimate its impact on the constant term of the energy resolution.
Abstract: The ionization signals in the liquid argon of the ATLAS electromagnetic calorimeter are studied in detail using cosmic muons. In particular, the drift time of the ionization electrons is measured and used to assess the intrinsic uniformity of the calorimeter gaps and estimate its impact on the constant term of the energy resolution. The drift times of electrons in the cells of the second layer of the calorimeter are uniform at the level of 1.3% in the barrel and 2.8% in the endcaps. This leads to an estimated contribution to the constant term of (0.29(-0.04)(+0.05))% in the barrel and (0.54(-0.04)(+0.06))% in the endcaps. The same data are used to measure the drift velocity of ionization electrons in liquid argon, which is found to be 4.61 +/- 0.07 mm/mu s at 88.5 K and 1 kV/mm.

31 citations



Journal ArticleDOI
TL;DR: The status of lung cancer clinical trials active in 2009 was reviewed by searching the ClinicalTrials.gov website, suggesting that less than 5% of patients diagnosed with lung cancer are enrolled on a therapeutic trial each year.



Journal ArticleDOI
TL;DR: This study evaluated the prognostic impact of TS gene copy number in NSCLC, especially with regard to histology, and determined the mean TS copies/nucleus/core.
Abstract: e21063 Background: Studies suggest that high TS expression associates with poor prognosis and confers resistance to antifolates, particularly pemetrexed. TS is essential for de novo production of d...

Journal ArticleDOI
TL;DR: The NaNose was incorporated in pulmonary “nodule clinics” where patients are evaluated for a suspicious lung nodule and its potential to distinguish between benign and malignant nodules was demonstrated.
Abstract: 10521 Background: There is no approved screening method for lung cancer and CT scanning has a high rate of false positives. Exhaled breath analysis for volatile organic compounds (VOCs) has the potential to distinguish between benign and malignant nodules. Recently, we showed that novel gold (Au) nanoparticles-based Artificial Olfactory System; NaNose, distinguishes between malignant (non-small lung cancer; NSCLC) and non-malignant human breaths and cell lines. In this study we incorporated the NaNose in our pulmonary “nodule clinics” where patients are evaluated for a suspicious lung nodule. Methods: 34 patients with lung nodules and 21 healthy subjects were tested for exhaled breath VOC profile. Patients were further evaluated as clinically appropriate. The exhaled breath was sampled by Eco Medics collecting system and the air passed through a Tenax SKC tube, which was analyzed for: (i) gas-chromatography/mass- spectrometry (GCMS) combined with solid phase micro-extraction (SPME) for determining the che...

Book ChapterDOI
01 Jan 2010
TL;DR: All the chemoprevention clinical trials have failed to show any clinical or histologic benefit with respect to lung cancer.
Abstract: The poor prognosis associated with lung cancer has stimulated substantial effort directed toward lung cancer prevention. As smoking prevention and cessation have proven difficult to achieve, many chemoprevention trials have been done during the last few decades. Such trials have focused on lung cancer survivors and high-risk groups including current and former heavy smokers with or without COPD. The aims of these trials were to reduce lung cancer incidence as well as to reduce/reverse premalignant changes in the bronchial epithelium. Unfortunately, till now all the chemoprevention clinical trials have failed to show any clinical or histologic benefit with respect to lung cancer.

Journal ArticleDOI
TL;DR: An international multidisciplinary workshop was held, including representatives from the patients’ advocacy groups, with the goal of identifying barriers for improvements for early stage disease, including perception of stigma and nihilism in the public, and slow accrual to clinical trials.