Radiotherapy for tumors of the stomach and gastroesophageal junction - a review of its role in multimodal therapy

There is broad consensus on surgical resection being the backbone of curative therapy of gastric- and gastroesophageal junction carcinoma. Nevertheless, details on therapeutic approaches in addition to surgery, such as chemotherapy, radiotherapy or radiochemotherapy are discussed controversially; especially whether external beam radiotherapy should be applied in addition to chemotherapy and surgery is debated in both entities and differs widely between regions and centers. Early landmark trials such as the Intergroup-0116 and the MAGIC trial must be interpreted in the context of potentially insufficient lymph node resection. Despite shortcomings of both trials, benefits on overall survival by radiochemotherapy and adjuvant chemotherapy were confirmed in populations of D2-resected gastric cancer patients by Asian trials. Recent results on junctional carcinoma patients strongly suggest a survival benefit of neoadjuvant radiochemotherapy in curatively resectable patients. An effect of chemotherapy in the perioperative setting as given in the MAGIC study has been confirmed by the ACCORD07 trial for junctional carcinomas; however both the studies by Stahl et al. and the excellent outcome in the CROSS trial as compared to all other therapeutic approaches indicate a superiority of neoadjuvant radiochemotherapy as compared to perioperative chemotherapy in junctional carcinoma patients. Surgery alone without neoadjuvant or perioperative therapy is considered suboptimal in patients with locally advanced disease. In gastric carcinoma patients, perioperative chemotherapy has not been compared to adjuvant radiochemotherapy in a randomized setting. Nevertheless, the results of the recently published ARTIST trial and the Chinese data by Zhu and coworkers, indicate a superiority of adjuvant radiochemotherapy as compared to adjuvant chemotherapy in terms of disease free survival in Asian patients with advanced gastric carcinoma. The ongoing CRITICS trial is supposed to provide reliable conclusions about which therapy should be preferred in Western patients with gastric carcinoma. If radiotherapy is performed, modern approaches such as intensity-modulated radiotherapy and image guidance should be applied, as these methods reduce dose to organs at risk and provide a more homogenous coverage of planning target volumes

Mirror Position Determination for the Alignment of Cherenkov Telescopes

Imaging Atmospheric Cherenkov Telescopes (IACTs) need imaging optics with large apertures to map the faint Cherenkov light emitted in extensive air showers onto their image sensors. Segmented reflectors fulfill these needs using mass produced and light weight mirror facets. However, as the overall image is the sum of the individual mirror facet images, alignment is important. Here we present a method to determine the mirror facet positions on a segmented reflector in a very direct way. Our method reconstructs the mirror facet positions from photographs and a laser distance meter measurement which goes from the center of the image sensor plane to the center of each mirror facet. We use our method to both align the mirror facet positions and to feed the measured positions into our IACT simulation. We demonstrate our implementation on the 4 m First Geiger-mode Avalanche Cherenkov Telescope (FACT).Comment: 11 figures, small ray tracing performance simulation, and implementation demonstratio

A High Docosahexaenoic Acid Diet Alters the Lung Inflammatory Response to Acute Dust Exposure

Agricultural workers are at risk for the development of acute and chronic lung diseases due to their exposure to organic agricultural dusts. A diet intervention using the omega-3 fatty acid docosahexaenoic acid (DHA) has been shown to be an effective therapeutic approach for alleviating a dust-induced inflammatory response. We thus hypothesized a high-DHA diet would alter the dust-induced inflammatory response through the increased production of specialized pro-resolving mediators (SPMs). Mice were pre-treated with a DHA-rich diet 4 weeks before being intranasally challenged with a single dose of an extract made from dust collected from a concentrated swine feeding operation (HDE). This omega-3-fatty-acid-rich diet led to reduced arachidonic acid levels in the blood, enhanced macrophage recruitment, and increased the production of the DHA-derived SPM Resolvin D1 (RvD1) in the lung following HDE exposure. An assessment of transcript-level changes in the immune response demonstrated significant differences in immune pathway activation and alterations of numerous macrophage-associated genes among HDE-challenged mice fed a high DHA diet. Our data indicate that consuming a DHA-rich diet leads to the enhanced production of SPMs during an acute inflammatory challenge to dust, supporting a role for dietary DHA supplementation as a potential therapeutic strategy for reducing dust-induced lung inflammation

Observation of inverse Compton emission from a long gamma-ray burst

Long-duration gamma-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectron volt-to-mega electronvoltband, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission(1,2). Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands(1-6). The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock(7-9). Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C(10,11). Here we report multifrequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 x 10(-6) to 10(12) electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs

The Genomic Signature of Crop-Wild Introgression in Maize

The evolutionary significance of hybridization and subsequent introgression has long been appreciated, but evaluation of the genome-wide effects of these phenomena has only recently become possible. Crop-wild study systems represent ideal opportunities to examine evolution through hybridization. For example, maize and the conspecific wild teosinte Zea mays ssp. mexicana, (hereafter, mexicana) are known to hybridize in the fields of highland Mexico. Despite widespread evidence of gene flow, maize and mexicana maintain distinct morphologies and have done so in sympatry for thousands of years. Neither the genomic extent nor the evolutionary importance of introgression between these taxa is understood. In this study we assessed patterns of genome-wide introgression based on 39,029 single nucleotide polymorphisms genotyped in 189 individuals from nine sympatric maize-mexicana populations and reference allopatric populations. While portions of the maize and mexicana genomes were particularly resistant to introgression (notably near known cross-incompatibility and domestication loci), we detected widespread evidence for introgression in both directions of gene flow. Through further characterization of these regions and preliminary growth chamber experiments, we found evidence suggestive of the incorporation of adaptive mexicana alleles into maize during its expansion to the highlands of central Mexico. In contrast, very little evidence was found for adaptive introgression from maize to mexicana. The methods we have applied here can be replicated widely, and such analyses have the potential to greatly informing our understanding of evolution through introgressive hybridization. Crop species, due to their exceptional genomic resources and frequent histories of spread into sympatry with relatives, should be particularly influential in these studies

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

FACT - Highlights from more than Five Years of Unbiased Monitoring at TeV Energies

The First G-APD Cherenkov Telescope (FACT) is monitoring blazars at TeV energies. Thanks to the observing strategy, the automatic operation and the usage of solid state photosensors (SiPM, aka G-APDs), the duty cycle of the instrument has been maximized and the observational gaps minimized. This provides a unprecedented, unbiased data sample of almost 9000~hours of data of which 2375 hours were taken in 2016. An automatic quick look analysis provides results with low latency on a public website. More than 40 alerts have been sent in the last three years based on this. To study the origin of the very high energy emission from blazars simultaneous multi-wavelength and multi-messenger observations are crucial to draw conclusions on the underlying emission mechanisms, e.g. to distinguish between leptonic and hadronic models. FACT not only participates in multi-wavelength studies, correlation studies with other instruments and multi-messenger studies, but also collects time-resolved spectral energy distributions using a target-of-opportunity program with X-ray satellites. At TeV energies, FACT provides an unprecedented, unbiased data sample. Using up to 1850 hours per source, the duty cycle of the sources and the characteristics of flares at TeV energies are studied. In the presentation, the highlights from more than five years of monitoring will be summarized including several flaring activities of Mrk 421, Mrk 501 and 1ES 1959+650.D. Dorner, J. Adam, M.L. Ahnen, D. Baack, M. Balbo, A. Biland, M. Blank, T. Bretz, a, K. Bruegge, M. Bulinski, J. Buss, A. Dmytriiev, S. Einecke, D. Elsaesser, C. Hempfling, T. Herbst, D. Hildebrand, L. Kortmann, L. Linhoff, M. Mahlke, a, K. Mannheim, S.A. Mueller, D. Neise, A. Neronov, M. Noethe, J. Oberkirch, A. Paravac, F. Pauss, W. Rhode, B. Schleicher, F. Schulz, A. Shukla, V. Sliusar, F. Temme, J. Thaele, R. Walte

Single photon extraction for FACT's SiPMs allows for novel IACT event representation

Imaging Atmospheric Cherenkov Telescopes provide large gamma-ray collection areas > 104 m2 and successfully probe the high energetic gamma-ray sky by observing extensive air-showers during the night. The First G-APD Cherenkov Telescope (FACT) explores silicon based photoelectric converters (called G-APDs or SiPMs) which provide more observation time with strong moonlight, a more stable photon gain over years of observations, and mechanically simpler imaging cameras. So far, the signal extraction methods used for FACT originate from sensors with no intrinsic quantized responses like photomultiplier tubes. This standard signal extraction is successfully used for the long time monitoring of the gamma-ray flux of bright blazars. However, we now challenge our classic signal extraction and explore single photon extraction methods to take advantage of the highly stable and quantized single photon responses of FACT’s SiPM sensors. Instead of having one main pulse with one arrival time and one photon equivalent extracted for each pixel, we extract the arrival times of all individual photons in a pixel’s time line which opens up a new dimension in time for representing extensive air-showers with an IACT.S. A. Mueller, J. Adam, M. L. Ahnen, D. Baack, M. Balbo, A. Biland, M. Blank, T. Bretz, K. Bruegge, J. Buss, A. Dmytriiev, D. Dorner, S. Einecke, D. Elsaesser, C. Hempfling, T. Herbst, D. Hildebrand, L. Kortmann, L. Linhoff, M. Mahlke, K. Mannheim, D. Neise, A. Neronov, M. Noethe, J. Oberkirch, A. Paravac, F. Pauss, W. Rhode, B. Schleicher, F. Schulz, A. Shukla, V. Sliusar, F. Temme, J. Thaele, R. Walte

Measuring the optical point spread function of FACT using the Cherenkov camera

FACT, the First G-APD Cherenkov Telescope, is an Imaging Air Cherenkov Telescope (IACT) operating since 2011 at the Observatorio del Roque de los Muchachos on the Canary Island of La Palma. As typical for IACTs, its reflector is comprised of smaller mirror facets and not protected by a dome. In the case of FACT, 30 hexagonal facets form a total mirror area of 9:5m². Hence, it is crucial to monitor the optical properties of this system and realign the facets if necessary. Up to now, measuring the Point Spread Function of FACT required human interaction to mount a screen and an optical camera. In this contribution, a new method to measure the optical Point Spread Function using directly the Cherenkov camera of the telescope is presented. Inspired by the method radio telescopes use to determine their resolution, the telescope is pointed towards a fixed position on the trajectory of a star. During the star’s passage through the field of view, the camera is read out using a fixed rate. In each event, the pedestal variance is determined for each pixel. This value is directly correlated with the amount of night sky background light a pixel received. Translating the time of the measurement to the position of the star in the camera enables to determine the optical point spread function from this measurement. As the measurement is done for each pixel along the trajectory of the star, the Point Spread Function can be determined not only for the camera center but for the entire field of view. In this contribution, the new method will also be compared with the existing methods of determining the optical Point Spread Function: direct measurement with an optical camera and the width of Muon ring events.M. Noethe, J. Adam, M. L. Ahnen, D. Baack, M. Balbo, A. Biland, M. Blank, T. Bretz, K. Bruegge, J. Buss, A. Dmytriiev, D. Dorner, S. Einecke, D. Elsaesser, C. Hempfling, T. Herbst, D. Hildebrand, L. Kortmann, L. Linhoff, M. Mahlke, K. Mannheim, S. A. Mueller, D. Neise, A. Neronov, J. Oberkirch, A. Paravac, F. Pauss, W. Rhode, B. Schleicher, F. Schulz, A. Shukla, V. Sliusar, F. Temme, J. Thaele, R. Walte