Fluorescence and Hybrid Detection Aperture of the Pierre Auger Observatory

The aperture of the Fluorescence Detector (FD) of the Pierre Auger Observatory is evaluated from simulated events using different detector configurations: mono, stereo, 3-FD and 4-FD. The trigger efficiency has been modeled using shower profiles with ground impacts in the field of view of a single telescope and studying the trigger response (at the different levels) by that telescope and by its neighbours. In addition, analysis cuts imposed by event reconstruction have been applied. The hybrid aperture is then derived for the Auger final extension. Taking into account the actual Surface Detector (SD) array configuration and its trigger response, the aperture is also calculated for a typical configuration of the present phase.Comment: contribution to the 29th International Cosmic Ray Conference, Pune, India, 3-10 August 200

Титульные страницы и содержание

Chronic severe somatoform disorder (SFD) is resistant to treatment. In a prospective observational study, we evaluated an intensive multidisciplinary treatment focusing on body-related mentalization and acceptance. Patients included in the study were 183 (146 women, 37 men) of 311 eligible patients with chronic severe SFD, referred consecutively to a specialized tertiary care center between 2002 and 2009. Primary outcome measures were somatic symptoms (SCL-90) and health-related quality of life (EuroQol 5-Dimensional [EQ-5D]). These measures were assessed four times before treatment (on intake, twice during an observation period, at start of treatment) and four times after treatment (during follow-up for 2 years). Multilevel analysis was used to separate effects of time (maturation) and treatment. Results revealed significant improvements in SCL-90 somatic symptoms (d = 0.51), EQ-5D index (d = 0.27), and EQ visual analogue scale (d = 0.56). Significant reductions were also observed in SCL-90 anxiety, depression, and overall psychopathology as well as in medical consumption associated with psychiatric illness (Trimbos/iMTA Questionnaire for Costs Associated With Psychiatric Illness). Large interindividual differences were found in treatment outcome. The long-term improvement seen in many patients suggests that intensive multidisciplinary tertiary care treatment is a useful approach to chronic severe SFD

Extraction of the atmospheric neutrino fluxes from experimental event rate data

The precise knowledge of the atmospheric neutrino fluxes is a key ingredient in the interpretation of the results from any atmospheric neutrino experiment. In the standard atmospheric neutrino data analysis, these fluxes are theoretical inputs obtained from sophisticated numerical calculations. In this contribution we present an alternative approach to the determination of the atmospheric neutrino fluxes based on the direct extraction from the experimental data on neutrino event rates. The extraction is achieved by means of a combination of artificial neural networks as interpolants and Monte Carlo methods.Comment: 6 pages, 2 figs, to appear in the proceedings of the 2nd International Conference on Quantum Theories and Renormalization Group in Gravity and Cosmology, Barcelona, July 200

Controlling the formation and stability of ultra-thin nickel silicides : an alloying strategy for preventing agglomeration

The electrical contact of the source and drain regions in state-of-the-art CMOS transistors is nowadays facilitated through NiSi, which is often alloyed with Pt in order to avoid morphological agglomeration of the silicide film. However, the solid-state reaction between as-deposited Ni and the Si substrate exhibits a peculiar change for as-deposited Ni films thinner than a critical thickness of t(c) = 5 nm. Whereas thicker films form polycrystalline NiSi upon annealing above 450 degrees C, thinner films form epitaxial NiSi2 films that exhibit a high resistance toward agglomeration. For industrial applications, it is therefore of utmost importance to assess the critical thickness with high certainty and find novel methodologies to either increase or decrease its value, depending on the aimed silicide formation. This paper investigates Ni films between 0 and 15 nm initial thickness by use of "thickness gradients," which provide semi-continuous information on silicide formation and stability as a function of as-deposited layer thickness. The alloying of these Ni layers with 10% Al, Co, Ge, Pd, or Pt renders a significant change in the phase sequence as a function of thickness and dependent on the alloying element. The addition of these ternary impurities therefore changes the critical thickness t(c). The results are discussed in the framework of classical nucleation theory

Історія польських поселень Володарсько-Волинського району

В даній роботі описано 10 сіл з переважаючим польським населенням, на що вказують архівні матеріали і опитування жителів сіл

Measuring diffuse neutrino fluxes with IceCube

In this paper the sensitivity of a future kilometer-sized neutrino detector to detect and measure the diffuse flux of high energy neutrinos is evaluated. Event rates in established detection channels, such as muon events from charged current muon neutrino interactions or cascade events from electron neutrino and tau neutrino interactions, are calculated using a detailed Monte Carlo simulation. Neutrino fluxes as expected from prompt charm decay in the atmosphere or from astrophysical sources such as Active Galactic Nuclei are modeled assuming power laws. The ability to measure the normalization and slope of these spectra is then analyzed. It is found that the cascade channel generally has a high sensitivity for the detection and characterization of the diffuse flux, when compared to what is expected for the upgoing- and downgoing-muon channels. A flux at the level of the Waxman-Bahcall upper bound should be detectable in all channels separately while a combination of the information of the different channels will allow detection of a flux more than one order of magnitude lower. Neutrinos from the prompt decay of charmed mesons in the atmosphere should be detectable in future measurements for all but the lowest predictions.Comment: 12 pages, 3 figure

EGFR fluorescence in situ hybridisation assay: guidelines for application to non-small-cell lung cancer

There is a need for predictive biomarkers that identify non-small-cell lung cancer (NSCLC) patients most likely to respond to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. There are numerous potential candidates, although none has been proven in prospective clinical trials. The EGFR gene copy number evaluated by fluorescence in situ hybridisation (FISH) has been highlighted as one of the most effective markers for sensitivity to EGFR TKIs in large phase III, randomised placebo-controlled trials and has been used in clinical settings to assist physicians in defining the therapeutic regimen. The EGFR FISH assay has technical challenges and it is critical that detailed guidelines are provided to help clinical laboratories in performing and interpreting the test. Excellent assay reproducibility and portability rates among laboratories are crucial to guarantee that accurate clinical decisions can be made for patients with NSCLC. This article discusses the consensus outcomes of a global workshop convened to discuss key technical issues and standardise reading strategies for the EGFR FISH assay of NSCLC tumour tissue

Community incidence of pathogen-specific gastroenteritis: reconstructing the surveillance pyramid for seven pathogens in seven European Union member states.

By building reconstruction models for a case of gastroenteritis in the general population moving through different steps of the surveillance pyramid we estimated that millions of illnesses occur annually in the European population, leading to thousands of hospitalizations. We used data on the healthcare system in seven European Union member states in relation to pathogen characteristics that influence healthcare seeking. Data on healthcare usage were obtained by harmonized cross-sectional surveys. The degree of under-diagnosis and underreporting varied by pathogen and country. Overall, underreporting and under-diagnosis were estimated to be lowest for Germany and Sweden, followed by Denmark, The Netherlands, UK, Italy and Poland. Across all countries, the incidence rate was highest for Campylobacter spp. and Salmonella spp. Incidence estimates resulting from the pyramid reconstruction approach are adjusted for biases due to different surveillance systems and are therefore a better basis for international comparisons than reported data

Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study

Background: Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate comprised of trastuzumab covalently bound to a linker drug containing duocarmycin. Preclinical studies showed promising antitumour activity in various models. In this first-in-human study, we assessed the safety and activity of trastuzumab duocarmazine in patients with advanced solid tumours. Methods: We did a phase 1 dose-escalation and dose-expansion study. The dose-escalation cohort comprised patients aged 18 years or older enrolled from three academic hospitals in Belgium, the Netherlands, and the UK with locally advanced or metastatic solid tumours with variable HER2 status who were refractory to standard cancer treatment. A separate cohort of patients were enrolled to the dose-expansion phase from 15 hospitals in Belgium, the Netherlands, Spain, and the UK. Dose-expansion cohorts included patients aged 18 years or older with breast, gastric, urothelial, or endometrial cancer with at least HER2 immunohistochemistry 1+ expression and measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST). Trastuzumab duocarmazine was administered intravenously on day 1 of each 3-week cycle. In the dose-escalation phase, trastuzumab duocarmazine was given at doses of 0.3 mg/kg to 2.4 mg/kg (3 + 3 design) until disease progression or unacceptable toxicity. The primary endpoint of the dose-escalation phase was to assess safety and ascertain the recommended phase 2 dose, which would be the dose used in the dose-expansion phase. The primary endpoint of the dose-expansion phase was the proportion of patients achieving an objective response (complete response or partial response), as assessed by the investigator using RECIST version 1.1. This ongoing study is registered with ClinicalTrials.gov, number NCT02277717, and is fully recruited. Findings: Between Oct 30, 2014, and April 2, 2018, 39 patients were enrolled and treated in the dose-escalation phase and 146 patients were enrolled and treated in the dose-expansion phase. One dose-limiting toxic effect (death from pneumonitis) occurred at the highest administered dose (2.4 mg/kg) in the dose-escalation phase. One further death occurred in the dose-escalation phase (1.5 mg/kg cohort) due to disease progression, which was attributed to general physical health decline. Grade 3-4 treatment-related adverse events reported more than once in the dose-escalation phase were keratitis (n=3) and fatigue (n=2). Based on all available data, the recommended phase 2 dose was set at 1.2 mg/kg. In the dose-expansion phase, treatment-related serious adverse events were reported in 16 (11%) of 146 patients, most commonly infusion-related reactions (two [1%]) and dyspnoea (two [1%]). The most common treatment-related adverse events (grades 1-4) were fatigue (48 [33%] of 146 patients), conjunctivitis (45 [31%]), and dry eye (45 [31%]). Most patients (104 [71%] of 146) had at least one ocular adverse event, with grade 3 events reported in ten (7%) of 146 patients. No patients died from treatment-related adverse events and four patients died due to disease progression, which were attributed to hepatic failure (n=1), upper gastrointestinal haemorrhage (n=1), neurological decompensation (n=1), and renal failure (n=1). In the breast cancer dose-expansion cohorts, 16 (33%, 95% CI 20.4-48.4) of 48 assessable patients with HER2-positive breast cancer achieved an objective response (all partial responses) according to RECIST. Nine (28%, 95% CI 13.8-46.8) of 32 patients with HER2-low, hormone receptor-positive breast cancer and six (40%, 16.3-67.6) of 15 patients with HER2-low, hormone receptor-negative breast cancer achieved an objective response (all partial responses). Partial responses were also observed in one (6%, 95% CI 0.2-30.2) of 16 patients with gastric cancer, four (25%, 7.3-52.4) of 16 patients with urothelial cancer, and five (39%, 13.9-68.4) of 13 patients with endometrial cancer. Interpretation: Trastuzumab duocarmazine shows notable clinical activity in heavily pretreated patients with HER2-expressing metastatic cancer, including HER2-positive trastuzumab emtansine-resistant and HER2-low breast cancer, with a manageable safety profile. Further investigation of trastuzumab duocarmazine for HER2-positive breast cancer is ongoing and trials for HER2-low breast cancer and other HER2-expressing cancers are in preparation. Copyright (C) 2019 Elsevier Ltd. All rights reserved