MWL observations of VHE blazars in 2006

In 2006 the MAGIC telescope observed the well known very high energy (VHE, > 80 GeV) blazars Mrk 421 and Mrk 501 in the course of multi-wavelength campaigns, comprising measurements in the optical, X-ray and VHE regime. MAGIC performed additional snapshot observations on Mrk 421 around the MWL campaigns and detected the source each night with high significance, establishing once more flux variability on nightly scales for this object. For certain nights, the integral flux exceeded the one of Crab significantly, whereas the truly simultaneous observations have been conducted in a rather low flux state. The MAGIC observations contemporaneous to XMM-Newton revealed clear intra-night variability. No significant correlation between the spectral index and the flux could be found for the nine days of observations. The VHE observations of Mrk 501 have been conducted during one of the lowest flux states ever measured by MAGIC for this object. The VHE and optical light curves do not show significant variability, whereas the flux in X-rays increased by about 50 %. In this contribution, the results of the MAGIC observations will be presented in detail.Comment: Contribution to the 31st ICRC, Lodz, Poland, July 200

Long term monitoring of bright TeV Blazars with the MAGIC telescope

The MAGIC telescope has performed long term monitoring observations of the bright TeV Blazars Mrk421, Mrk501 and 1ES1959+650. Up to 40 observations, 30 to 60 minutes each have been performed for each source evenly distributed over the observable period of the year. The sensitivity of MAGIC is sufficient to establish a flux level of 25% of the Crab flux for each measurement. These observations are well suited to trigger multiwavelength ToO observations and the overall collected data allow an unbiased study of the flaring statistics of the observed AGNs.Comment: 4 pages, 4 figures, to appear in the proceedings of the 30th International Cosmic Ray Conference, Merida, July 200

Monitoring overall survival in pivotal trials in indolent cancers

Indolent cancers are characterized by long overall survival (OS) times. Therefore, powering a clinical trial to provide definitive assessment of the effects of an experimental intervention on OS in a reasonable timeframe is generally infeasible. Instead, the primary outcome in many pivotal trials is an intermediate clinical response such as progression-free survival (PFS). In several recently reported pivotal trials of interventions for indolent cancers that yielded promising results on an intermediate outcome, however, more mature data or post-approval trials showed concerning OS trends. These problematic results have prompted a keen interest in quantitative approaches for monitoring OS that can support regulatory decision-making related to the risk of an unacceptably large detrimental effect on OS. For example, the US Food and Drug Administration, the American Association for Cancer Research, and the American Statistical Association recently organized a one-day multi-stakeholder workshop entitled 'Overall Survival in Oncology Clinical Trials'. In this paper, we propose OS monitoring guidelines tailored for the setting of indolent cancers. Our pragmatic approach is modeled, in part, on the monitoring guidelines the FDA has used in cardiovascular safety trials conducted in Type 2 Diabetes Mellitus. We illustrate proposals through application to several examples informed by actual case studies.Comment: 13 pages, 5 table

FACT - The First G-APD Cherenkov Telescope: Status and Results

The First G-APD Cherenkov telescope (FACT) is the first telescope using silicon photon detectors (G-APD aka. SiPM). It is built on the mount of the HEGRA CT3 telescope, still located at the Observatorio del Roque de los Muchachos, and it is successfully in operation since Oct. 2011. The use of Silicon devices promises a higher photon detection efficiency, more robustness and higher precision than photo-multiplier tubes. The FACT collaboration is investigating with which precision these devices can be operated on the long-term. Currently, the telescope is successfully operated from remote and robotic operation is under development. During the past months of operation, the foreseen monitoring program of the brightest known TeV blazars has been carried out, and first physics results have been obtained including a strong flare of Mrk501. An instantaneous flare alert system is already in a testing phase. This presentation will give an overview of the project and summarize its goals, status and first results

FACT -- Operation of the First G-APD Cherenkov Telescope

Since more than two years, the First G-APD Cherenkov Telescope (FACT) is operating successfully at the Canary Island of La Palma. Apart from its purpose to serve as a monitoring facility for the brightest TeV blazars, it was built as a major step to establish solid state photon counters as detectors in Cherenkov astronomy. The camera of the First G-APD Cherenkov Telesope comprises 1440 Geiger-mode avalanche photo diodes (G-APD aka. MPPC or SiPM) for photon detection. Since properties as the gain of G-APDs depend on temperature and the applied voltage, a real-time feedback system has been developed and implemented. To correct for the change introduced by temperature, several sensors have been placed close to the photon detectors. Their read out is used to calculate a corresponding voltage offset. In addition to temperature changes, changing current introduces a voltage drop in the supporting resistor network. To correct changes in the voltage drop introduced by varying photon flux from the night-sky background, the current is measured and the voltage drop calculated. To check the stability of the G-APD properties, dark count spectra with high statistics have been taken under different environmental conditions and been evaluated. The maximum data rate delivered by the camera is about 240 MB/s. The recorded data, which can exceed 1 TB in a moonless night, is compressed in real-time with a proprietary loss-less algorithm. The performance is better than gzip by almost a factor of two in compression ratio and speed. In total, two to three CPU cores are needed for data taking. In parallel, a quick-look analysis of the recently recorded data is executed on a second machine. Its result is publicly available within a few minutes after the data were taken. [...]Comment: 19th IEEE Real-Time Conference, Nara, Japan (2014

Comparative evaluation of anopheline sampling methods in three localities in Indonesia

Background: The effectiveness of vector control efforts can vary based on the interventions used and local mosquito behaviour and adaptability. In many settings, biting patterns of Anopheles mosquitoes can shift in response to interventions targeting indoor-biting mosquitoes, often resulting in higher proportions of mosquitoes feeding outside or at times when people are not protected. These behaviourally resistant mosquitoes have been shown to sustain residual malaria transmission and limit control efforts. Therefore, it is important to accurately sample mosquitoes to understand their behaviour. Methods: A variety of traps were evaluated in three geographically diverse sites in malaria-endemic Indonesia to investigate local mosquito feeding behaviour and determine effective traps for surveillance. Results: Eight traps were evaluated in three sites: Canti village, Lampung, Kaliharjo village, Purworejo, and Saketa village, Halmahera, Indonesia, including the gold standard human landing collection (HLC) and a variety of traps targeting host-seeking and resting mosquitoes both indoors and outdoors. Trapping, using indoor and outdoor HLC, the Ifakara tent trap C, goat and human-occupied tents, resting pots and boxes, and CDC miniature light traps was conducted for 16 nights in two sites and 8 nights in a third site, using a Latin square design. Trap efficacy varied by site, with outdoor HLC yielding the highest catch rates in Canti and Kaliharjo and a goat-baited tent trap proving most effective in Saketa. In Canti village, anthropophilic Anopheles sundaicus were caught indoors and outdoors using HLCs, peaking in the early morning. In Kaliharjo, a variety of mosquitoes were caught, mostly outdoors throughout the night. HLC was ineffective in Saketa, the only site where a goat-baited tent trap was tested. This trap was effective in catching zoophilic vectors outdoors before midnight. Conclusions: Different trapping methods were suitable for different species, likely reflecting differences in behaviour among species. The three villages, each located on a different island in the Indonesian archipelago, contained mosquito populations with unique behaviours. These data suggest that the effectiveness of specific vector monitoring and control measures may vary by location

Advanced Methods for Dose and Regimen Finding During Drug Development: Summary of the EMA/EFPIA Workshop on Dose Finding (London 4-5 December 2014)

Inadequate dose selection for confirmatory trials is currently still one of the most challenging issues in drug development, as illustrated by high rates of late-stage attritions in clinical development and postmarketing commitments required by regulatory institutions. In an effort to shift the current paradigm in dose and regimen selection and highlight the availability and usefulness of well-established and regulatory-acceptable methods, the European Medicines Agency (EMA) in collaboration with the European Federation of Pharmaceutical Industries Association (EFPIA) hosted a multistakeholder workshop on dose finding (London 4-5 December 2014). Some methodologies that could constitute a toolkit for drug developers and regulators were presented. These methods are described in the present report: they include five advanced methods for data analysis (empirical regression models, pharmacometrics models, quantitative systems pharmacology models, MCP-Mod, and model averaging) and three methods for study design optimization (Fisher information matrix (FIM)-based methods, clinical trial simulations, and adaptive studies). Pairwise comparisons were also discussed during the workshop; however, mostly for historical reasons. This paper discusses the added value and limitations of these methods as well as challenges for their implementation. Some applications in different therapeutic areas are also summarized, in line with the discussions at the workshop. There was agreement at the workshop on the fact that selection of dose for phase III is an estimation problem and should not be addressed via hypothesis testing. Dose selection for phase III trials should be informed by well-designed dose-finding studies; however, the specific choice of method(s) will depend on several aspects and it is not possible to recommend a generalized decision tree. There are many valuable methods available, the methods are not mutually exclusive, and they should be used in conjunction to ensure a scientifically rigorous understanding of the dosing rationale

Observation of Pulsed Gamma-rays Above 25 GeV from the Crab Pulsar with MAGIC

One fundamental question about pulsars concerns the mechanism of their pulsed electromagnetic emission. Measuring the high-end region of a pulsar's spectrum would shed light on this question. By developing a new electronic trigger, we lowered the threshold of the Major Atmospheric gamma-ray Imaging Cherenkov (MAGIC) telescope to 25 GeV. In this configuration, we detected pulsed gamma-rays from the Crab pulsar that were greater than 25 GeV, revealing a relatively high cutoff energy in the phase-averaged spectrum. This indicates that the emission occurs far out in the magnetosphere, hence excluding the polar-cap scenario as a possible explanation of our measurement. The high cutoff energy also challenges the slot-gap scenario.Comment: Slight modification of the analysis: Fitting a more general function to the combined data set of COMPTEL, EGRET and MAGIC. Final result and conclusion is unchange

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO