Emerging concepts in pancreatic cancer medicine: targeting the tumor stroma

Pancreatic ductal adenocarcinoma is a stroma-rich and highly challenging cancer to treat. Over recent years, it has become increasingly evident that the complex network of soluble cytokines, growth factors, proteases, and components of the extracellular matrix collaboratively interact within the tumor microenvironment, sustaining and driving cancer cell proliferation, invasion, and early metastasis. More recently, the tumor microenvironment has also been appreciated to mediate therapeutic resistance in pancreatic ductal adenocarcinoma, thus opening numerous avenues for novel therapeutic explorations. Inert and soluble components of the tumor stroma have been targeted in order to break down the extracellular matrix scaffold, relieve vessel compression, and increase drug delivery to hypovascular tumors. Moreover, targeting of antiapoptotic, immunosuppressive, and pro-proliferative effects of the tumor stroma provides novel vantage points of attack. This review focuses on current and future developments in pancreatic cancer medicine, with a particular emphasis on biophysical and biochemical approaches that target the tumor microenvironment

Co-ordination and management of chronic conditions in Europe:the role of primary care.

Healthcare systems in Europe struggle with inadequate co-ordination of care for people with chronic conditions. Moreover, there is a considerable evidence gap in the treatment of chronic conditions, lack of self-management, variation in quality of care, lack of preventive care, increasing costs for chronic care, and inefficient use of resources. In order to overcome these problems, several approaches to improve the management and co-ordination of chronic conditions have been developed in European healthcare systems. These approaches endeavour to improve self-management support for patients, develop clinical information systems and change the organisation of health care. Changes in the delivery system design and the development of decision support systems are less common. Almost as a rule, the link between healthcare services and community resources and policies is missing. Most importantly, the integration between the six components of the chronic care model remains an important challenge for the future. We find that the position of primary care in healthcare systems is an important factor for the development and implementation of new approaches to manage and coordinate chronic conditions. Our analysis supports the notion that countries with a strong primary care system tend to develop more comprehensive models to manage and co-ordinate chronic conditions

Search for Sub-TeV Gamma Rays Coincident with BATSE Gamma Ray Bursts

Project GRAND is a 100m x 100m air shower array of proportional wire chambers (PWCs). There are 64 stations each with eight 1.29 m^2 PWC planes arranged in four orthogonal pairs placed vertically above one another to geometrically measure the angles of charged secondaries. A steel plate above the bottom pair of PWCs differentiates muons (which pass undeflected through the steel) from non-penetrating particles. FLUKA Monte Carlo studies show that a TeV gamma ray striking the atmosphere at normal incidence produces 0.23 muons which reach ground level where their angles and identities are measured. Thus, paradoxically, secondary muons are used as a signature for gamma ray primaries. The data are examined for possible angular and time coincidences with eight gamma ray bursts (GRBs) detected by BATSE. Seven of the GRBs were selected because of their good acceptance by GRAND and high BATSE Fluence. The eighth GRB was added due to its possible coincident detection by Milagrito. For each of the eight candidate GRBs, the number of excess counts during the BATSE T90 time interval and within plus or minus five degrees of BATSE's direction was obtained. The highest statistical significance reported in this paper (2.7 sigma) is for the event that was predicted to be the most likely to be observed (GRB 971110).Comment: To be presented at the XXVIII International Cosmic Ray Conference, Tsukuba, Japa

"Last-Mile" preparation for a potential disaster

Extreme natural events, like e.g. tsunamis or earthquakes, regularly lead to catastrophes with dramatic consequences. In recent years natural disasters caused hundreds of thousands of deaths, destruction of infrastructure, disruption of economic activity and loss of billions of dollars worth of property and thus revealed considerable deficits hindering their effective management: Needs for stakeholders, decision-makers as well as for persons concerned include systematic risk identification and evaluation, a way to assess countermeasures, awareness raising and decision support systems to be employed before, during and after crisis situations. The overall goal of this study focuses on interdisciplinary integration of various scientific disciplines to contribute to a tsunami early warning information system. In comparison to most studies our focus is on high-end geometric and thematic analysis to meet the requirements of small-scale, heterogeneous and complex coastal urban systems. Data, methods and results from engineering, remote sensing and social sciences are interlinked and provide comprehensive information for disaster risk assessment, management and reduction. In detail, we combine inundation modeling, urban morphology analysis, population assessment, socio-economic analysis of the population and evacuation modeling. The interdisciplinary results eventually lead to recommendations for mitigation strategies in the fields of spatial planning or coping capacity

Signal recognition and background suppression by matched filters and neural networks for Tunka-Rex

The Tunka Radio Extension (Tunka-Rex) is a digital antenna array, which measures the radio emission of the cosmic-ray air-showers in the frequency band of 30-80 MHz. Tunka-Rex is co-located with TAIGA experiment in Siberia and consists of 63 antennas, 57 of them are in a densely instrumented area of about 1 km\textsuperscript{2}. In the present work we discuss the improvements of the signal reconstruction applied for the Tunka-Rex. At the first stage we implemented matched filtering using averaged signals as template. The simulation study has shown that matched filtering allows one to decrease the threshold of signal detection and increase its purity. However, the maximum performance of matched filtering is achievable only in case of white noise, while in reality the noise is not fully random due to different reasons. To recognize hidden features of the noise and treat them, we decided to use convolutional neural network with autoencoder architecture. Taking the recorded trace as an input, the autoencoder returns denoised trace, i.e. removes all signal-unrelated amplitudes. We present the comparison between standard method of signal reconstruction, matched filtering and autoencoder, and discuss the prospects of application of neural networks for lowering the threshold of digital antenna arrays for cosmic-ray detection.Comment: ARENA2018 proceeding

Current Status and New Challenges of The Tunka Radio Extension

The Tunka Radio Extension (Tunka-Rex) is an antenna array spread over an area of about 1~km$^2$. The array is placed at the Tunka Advanced Instrument for cosmic rays and Gamma Astronomy (TAIGA) and detects the radio emission of air showers in the band of 30 to 80~MHz. During the last years it was shown that a sparse array such as Tunka-Rex is capable of reconstructing the parameters of the primary particle as accurate as the modern instruments. Based on these results we continue developing our data analysis. Our next goal is the reconstruction of cosmic-ray energy spectrum observed only by a radio instrument. Taking a step towards it, we develop a model of aperture of our instrument and test it against hybrid TAIGA observations and Monte-Carlo simulations. In the present work we give an overview of the current status and results for the last five years of operation of Tunka-Rex and discuss prospects of the cosmic-ray energy estimation with sparse radio arrays.Comment: Proceedings of E+CRS 201

Improved measurements of the energy and shower maximum of cosmic rays with Tunka-Rex

The Tunka Radio Extension (Tunka-Rex) is an array of 63 antennas located in the Tunka Valley, Siberia. It detects radio pulses in the 30-80 MHz band produced during the air-shower development. As shown by Tunka-Rex, a sparse radio array with about 200 m spacing is able to reconstruct the energy and the depth of the shower maximum with satisfactory precision using simple methods based on parameters of the lateral distribution of amplitudes. The LOFAR experiment has shown that a sophisticated treatment of all individually measured amplitudes of a dense antenna array can make the precision comparable with the resolution of existing optical techniques. We develop these ideas further and present a method based on the treatment of time series of measured signals, i.e. each antenna station provides several points (trace) instead of a single one (amplitude or power). We use the measured shower axis and energy as input for CoREAS simulations: for each measured event we simulate a set of air-showers with proton, helium, nitrogen and iron as primary particle (each primary is simulated about ten times to cover fluctuations in the shower maximum due to the first interaction). Simulated radio pulses are processed with the Tunka-Rex detector response and convoluted with the measured signals. A likelihood fit determines how well the simulated event fits to the measured one. The positions of the shower maxima are defined from the distribution of chi-square values of these fits. When using this improved method instead of the standard one, firstly, the shower maximum of more events can be reconstructed, secondly, the resolution is increased. The performance of the method is demonstrated on the data acquired by the Tunka-Rex detector in 2012-2014.Comment: Proceedings of the 35th ICRC 2017, Busan, Kore