Abstract
Aerosol levels influence the wavelength dependent transmission properties of the atmosphere. Variations in aerosol levels therefore affect the amount of Cherenkov light from air-showers that ...can reach an atmospheric Cherenkov detector. As the amount of detected Cherenkov light is directly related to a primary shower particle’s energy, deviations between actual and assumed atmospheric transmission properties yield errors in reconstructed particle energies as well as energy axes of instrument response functions. In this work, a scheme is presented to assess this influence and potentially reduce related errors in the air-shower reconstruction. The proposed scheme relies on estimations or measurements of the aerosol optical depth and atmospheric density profile which are then used in radiative transfer simulations to generate atmospheric transmission profiles. As the scheme furthermore uses detector specific quantum efficiencies and generalised shower evolution models, it does not rely on detailed Monte Carlo simulations for the different atmospheric conditions but only on the transmission profile which the initial shower reconstruction algorithm is based on. The approach is derived and presented on the example of the H.E.S.S. experiment which employs imaging atmospheric Cherenkov telescopes in the Khomas Highland of Namibia to detect gamma rays in the GeV to TeV energy range.
Ground based γ-ray observations with Imaging Atmospheric Cherenkov Telescopes (IACTs) play a significant role in the discovery of very high energy (E > 100 GeV) γ-ray emitters. The analysis of IACT ...data demands a highly efficient background rejection technique, as well as methods to accurately determine the position of its source in the sky and the energy of the recorded γ-ray. We present results for background rejection and signal direction reconstruction from first studies of a novel data analysis scheme for IACT measurements. The new analysis is based on a set of Convolutional Neural Networks (CNNs) applied to images from the four H.E.S.S. phase-I telescopes. As the H.E.S.S. cameras pixels are arranged in a hexagonal array, we demonstrate two ways to use such image data to train CNNs: by resampling the images to a square grid and by applying modified convolution kernels that conserve the hexagonal grid properties.
The networks were trained on sets of Monte-Carlo simulated events and tested on both simulations and measured data from the H.E.S.S. array. A comparison between the CNN analysis to current state-of-the-art algorithms reveals a clear improvement in background rejection performance. When applied to H.E.S.S. observation data, the CNN direction reconstruction performs at a similar level as traditional methods. These results serve as a proof-of-concept for the application of CNNs to the analysis of events recorded by IACTs.
Observations of astrophysical transients have brought many novel discoveries and provided new insights into the physical processes at work under extreme conditions in the Universe. Multi-wavelength ...and multi-messenger observations of variable objects require dedicated procedures and follow-up systems capable of digesting and reacting to external alerts to execute coordinated follow-up campaigns. The main functions of such follow-up systems are the processing, filtering, and ranking of the incoming alerts, the fully automated rapid execution of the observations according to an observation strategy tailored to the instrument, and real-time data analysis with feedback to the operators and other instruments. The High Energy Stereoscopic System (H.E.S.S.) has been searching for transient phenomena since its inauguration in 2003. In this paper, we describe the transients follow-up system of H.E.S.S. which became operational in 2016. The system allows H.E.S.S. to conduct a more versatile, optimised, and largely autonomous transient follow-up programme, combining all major functionalities in one systematic approach. We describe the design, central functionalities, and interfaces of the follow-up system in general and its three main components in detail: the Target of Opportunity (ToO) alert system, the data acquisition and central control system, and the real-time analysis. We highlight architectural decisions and features that enable fully automatic ToO follow-up and indicate key performance metrics of the subsystems. We discuss the system's capabilities and highlight the need for a fine-tuned interplay of the different subsystems in order to react quickly and reliably. Lessons learnt from the development, integration, and operation of the follow-up system are reviewed in light of new and large science infrastructures and associated challenges in this exciting new era of inter-operable astronomy.
The central region of the Milky Way is one of the foremost locations to look for dark matter (DM) signatures. We report the first results on a search for DM particle annihilation signals using new ...observations from an unprecedented γ -ray survey of the Galactic Center (GC) region, i.e., the Inner Galaxy Survey, at very high energies ( ≳100 GeV ) performed with the H.E.S.S. array of five ground-based Cherenkov telescopes. No significant γ -ray excess is found in the search region of the 2014–2020 dataset and a profile likelihood ratio analysis is carried out to set exclusion limits on the annihilation cross section ⟨ σv ⟩ . Assuming Einasto and Navarro-Frenk-White (NFW) DM density profiles at the GC, these constraints are the strongest obtained so far in the TeV DM mass range. For the Einasto profile, the constraints reach ⟨ σv ⟩ values of 3.7×10-26 cm3 s -1 for 1.5 TeV DM mass in the W+W- annihilation channel, and 1.2×10-26 cm3 s -1 for 0.7 TeV DM mass in the τ+τ- annihilation channel. With the H.E.S.S. Inner Galaxy Survey, ground-based γ -ray observations thus probe ⟨ σv ⟩ values expected from thermal-relic annihilating TeV DM particles.
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Abstract Magnetic fields in galaxies and galaxy clusters are believed to be the result of the amplification of intergalactic seed fields during the formation of large-scale structures in the ...universe. However, the origin, strength, and morphology of this intergalactic magnetic field (IGMF) remain unknown. Lower limits on (or indirect detection of) the IGMF can be obtained from observations of high-energy gamma rays from distant blazars. Gamma rays interact with the extragalactic background light to produce electron−positron pairs, which can subsequently initiate electromagnetic cascades. The gamma-ray signature of the cascade depends on the IGMF since it deflects the pairs. Here we report on a new search for this cascade emission using a combined data set from the Fermi Large Area Telescope and the High Energy Stereoscopic System. Using state-of-the-art Monte Carlo predictions for the cascade signal, our results place a lower limit on the IGMF of B > 7.1 × 10 −16 G for a coherence length of 1 Mpc even when blazar duty cycles as short as 10 yr are assumed. This improves on previous lower limits by a factor of 2. For longer duty cycles of 10 4 (10 7 ) yr, IGMF strengths below 1.8 × 10 −14 G (3.9 × 10 −14 G) are excluded, which rules out specific models for IGMF generation in the early universe.
Significant adverse events (AE) during cancer therapy disrupt treatment and escalate to emergency admissions. Approaches to improve the timeliness and accuracy of AE reporting may improve safety and ...reduce health service costs. Reporting AE via patient reported outcomes (PROs), can improve clinician–patient communication and making data available to clinicians in ‘real-time’ using electronic PROs (ePROs) could potentially transform clinical practice by providing easily accessible records to guide treatment decisions. This manuscript describes the development of eRAPID (electronic patient self-Reporting of Adverse-events: Patient Information and aDvice) is a National Institute for Health Research-funded programme, a system for patients to self-report and manage AE online during and after cancer treatment.
A multidisciplinary team of IT experts, staff and patients developed using agile principles a secure web application interface (QStore) between an existing online questionnaire builder (QTool) displaying real-time ePRO data to clinicians in the electronic patient record at Leeds Teaching Hospitals NHS Trust. Hierarchical algorithms were developed corresponding to Common Terminology Criteria for Adverse Events grading using the QTool question dependency function. Patient advocates (N = 9), patients (N = 13), and staff (N = 19) usability tested the system reporting combinations of AE.
The eRAPID system allows patients to report AE from home on PC, tablet or any web enabled device securely during treatment. The system generates immediate self-management advice for low or moderate AE and for severe AE advice to contact the hospital immediately. Clinicians can view patient AE data in the electronic patient record and receive email notifications when patients report severe AE.
Evaluation of the system in a randomised controlled trial in breast, gynaecological and colorectal cancer patients undergoing systemic therapy is currently underway. To adapt eRAPID for different treatment groups, pilot studies are being undertaken with patients receiving pelvic radiotherapy and upper gastrointestinal surgery.
ISRCTN88520246.
Observations of astrophysical transients have brought many novel discoveries and provided new insights into physical processes at work under extreme conditions in the Universe. Multi-wavelength and ...multi-messenger observations of variable objects require dedicated procedures and follow-up systems capable of digesting and reacting to external alerts to execute coordinated follow-up campaigns. The main functions of such follow-up systems are the processing, filtering, and ranking of the incoming alerts, the fully automated rapid execution of the observations according to an observation strategy tailored to the instrument, and real-time data analysis with feedback to the operators and other instruments. H.E.S.S. has been searching for transient phenomena since its inauguration in 2003. In this paper, we describe the transients follow-up system of H.E.S.S. which became operational in 2016. The system allows H.E.S.S. to conduct a more versatile, optimised, and largely autonomous transient follow-up program, combining all major functionalities in one systematic approach. We describe the design, central functionalities, and interfaces of the follow-up system in general and its three main components in detail: the Target of Opportunity (ToO) alert system, the data acquisition and central control system, and the real-time analysis. We highlight architectural decisions and features that enable fully automatic ToO follow-up and indicate key performance metrics of the sub-systems. We discuss the system's capabilities and highlight the need for a fine-tuned interplay of the different sub-systems in order to react quickly and reliably. Lessons learned from the development, integration, and operation of the follow-up system are reviewed in light of new and large science infrastructures and associated challenges in this exciting new era of inter-operable astronomy.
HexagDLy is a Python-library extending the PyTorch deep learning framework with convolution and pooling operations on hexagonal grids. It aims to ease the access to convolutional neural networks for ...applications that rely on hexagonally sampled data as, for example, commonly found in ground-based astroparticle physics experiments.
Increased baseline carcinoembryonic antigen (CEA) serum level is associated with inferior overall survival (OS) in metastatic colorectal cancer (mCRC). However, limited data exist on its predictive ...relevance for targeted therapies. Therefore, we analysed its relevance in FIRE-3, a randomised phase III study.
FIRE-3 evaluated first-line FOLFIRI plus cetuximab (FOLFIRI/Cet) versus FOLFIRI plus bevacizumab (FOLFIRI/Bev) in mCRC patients with RAS-WT tumour (i.e. wild-type in KRAS and NRAS exons 2–4). Herein, the impact of CEA on patient outcome was investigated.
Of 400 patients, 356 (89.0%) were evaluable for CEA. High CEA (>10 ng/ml; N = 237) compared to low CEA (≤10 ng/ml; N = 119) was associated with shorter OS in the FOLFIRI/Bev arm (hazard ratio HR = 1.50; P = 0.036), while no significant OS difference was observed in the FOLFIRI/Cet arm (HR = 1.07; P = 0.74). In patients with high CEA, FOLFIRI/Cet compared to FOLFIRI/Bev showed a greater OS benefit (HR = 0.56; P < 0.001) than in patients with low CEA (HR = 0.78; P = 0.30). Furthermore, FOLFIRI/Cet exhibited significantly superior objective response rate in patients with high CEA (odds ratio = 2.21; P = 0.006) in contrast to patients with low CEA (odds ratio = 0.90; P = 0.85).
In patients with RAS-WT mCRC receiving first-line chemotherapy with FOLFIRI/Cet versus FOLFIRI/Bev, elevated CEA was associated with inferior survival in the bevacizumab arm, while this was not the case when cetuximab was applied. Comparison of OS and objective response rate according to treatment arms indicated that cetuximab was greatly superior to bevacizumab in patients with elevated CEA, while this effect was markedly lower and lost statistical significance in patients with low CEA.
•High baseline CEA impacts survival in patients with metastatic colorectal cancer.•In FIRE-3, high baseline CEA led to shorter survival in FOLFIRI+bevacizumab arm.•Contrary, high baseline CEA did not show shorter survival in FOLFIRI+cetuximab arm.•Survival benefit of FOLFIRI+cetuximab over FOLFIRI+bevacizumab depended on CEA.•High baseline CEA may predict benefit from FOLFIRI+cetuximab over FOLFIRI+bevacizumab.
Cetuximab-induced skin toxicity (Cet-ST) is positively associated with outcome in metastatic colorectal cancer (mCRC). Besides its predictive relevance for targeted therapy, we investigated its ...prognostic impact with early tumor shrinkage (ETS) ≥20%, another on-treatment surrogate for clinical outcome in FIRE-3.
FIRE-3 evaluated first-line FOLFIRI (folinic acid, fluorouracil and irinotecan) plus cetuximab (FOLFIRI/Cet) versus FOLFIRI plus bevacizumab (FOLFIRI/Bev) in mCRC patients with RAS-WT tumors (i.e. wild-type in KRAS and NRAS exons 2–4). Retrospective data on Cet-ST that occurred during cycles 1–3 of treatment were correlated with efficacy endpoints, including ETS. To control for guarantee-time bias, only patients who had completed three or more treatment cycles were considered.
Of 199 patients treated with FOLFIRI/Cet, 181 (91.0%) completed three or more treatment cycles. A significant survival benefit of FOLFIRI/Cet over FOLFIRI/Bev was only evident in patients developing Cet-ST grade 2–3 41.0 versus 26.6 months; hazard ratio (HR) = 0.73; 95% confidence interval (CI): 0.61–0.87; P < 0.001 compared with Cet-ST grade 0–1 (HR = 0.90; 95% CI: 0.67–1.20; P = 0.48). Regarding prognosis, Cet-ST grade 2–3 (n = 75; 41.4%), compared with Cet-ST grade 0–1 (n = 106; 58.6%), was associated with prolonged overall survival (OS; HR = 0.62; 95% CI: 0.42–0.91; P = 0.01). In multivariate analysis, both Cet-ST (HR = 0.66; 95% CI: 0.50–0.87; P = 0.003) and ETS (HR = 0.55; 95% CI: 0.41–0.74; P < 0.0001) were independently prognostic for OS. Absence of both Cet-ST grade ≥2 and ETS identified a subgroup of patients with very poor prognosis (median OS 15.1 months).
In FIRE-3, the addition of cetuximab to FOLFIRI was associated with superior OS compared with FOLFIRI/Bev only in patients developing Cet-ST grade ≥2. Regarding prognostic relevance, both Cet-ST and ETS were independent and early predictors of survival. The present analysis supports that a combined evaluation of on-treatment parameters such as Cet-ST and ETS may help to guide treatment of mCRC.
•Cetuximab-induced skin toxicity positively correlated with survival in patients with metastatic colorectal cancer.•Cetuximab-induced skin toxicity predicted benefit from FOLFIRI plus cetuximab over FOLFIRI plus bevacizumab.•Cetuximab-induced skin toxicity and early tumor shrinkage predicted survival independently in multivariate analysis.•A combined evaluation of Cet-ST and ETS may help to guide treatment of metastatic colorectal cancer.
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