Treatment goals and changes over time in older patients with non-curable cancer

PURPOSE: To investigate the treatment goals of older patients with non-curable cancer, whether those goals changed over time, and if so, what triggered those changes. METHODS: We performed a descriptive and qualitative analysis using the Outcome Prioritization Tool (OPT) to assess patient goals across four conversations with general practitioners (GPs) over 6 months. Text entries from electronic patient records (hospital and general practice) were then analyzed qualitatively for this period. RESULTS: Of the 29 included patients, 10 (34%) rated extending life and 9 (31%) rated maintaining independence as their most important goals. Patients in the last year before death (late phase) prioritized extending life less often (3 patients; 21%) than those in the early phase (7 patients; 47%). Goals changed for 16 patients during follow-up (12 in the late phase). Qualitative analysis revealed three themes that explained the baseline OPT scores (prioritizing a specific goal, rating a goal as unimportant, and treatment choices related to goals). Another three themes related to changes in OPT scores (symptoms, disease course, and life events) and stability of OPT scores (stable situation, disease-unrelated motivation, and stability despite symptoms). CONCLUSION: Patients most often prioritized extending life as the most important goal. However, priorities differed in the late phase of the disease, leading to changed goals. Triggers for change related to both the disease (e.g., symptoms and course) and to other life events. We therefore recommend that goals should be discussed repeatedly, especially near the end of life. TRIAL REGISTRATION: OPTion study: NTR5419

A major electronics upgrade for the H.E.S.S. Cherenkov telescopes 1-4

The High Energy Stereoscopic System (H.E.S.S.) is an array of imaging atmospheric Cherenkov telescopes (IACTs) located in the Khomas Highland in Namibia. It consists of four 12-m telescopes (CT1-4), which started operations in 2003, and a 28-m diameter one (CT5), which was brought online in 2012. It is the only IACT system featuring telescopes of different sizes, which provides sensitivity for gamma rays across a very wide energy range, from ~30 GeV up to ~100 TeV. Since the camera electronics of CT1-4 are much older than the one of CT5, an upgrade is being carried out; first deployment was in 2015, full operation is planned for 2016. The goals of this upgrade are threefold: reducing the dead time of the cameras, improving the overall performance of the array and reducing the system failure rate related to aging. Upon completion, the upgrade will assure the continuous operation of H.E.S.S. at its full sensitivity until and possibly beyond the advent of CTA. In the design of the new components, several CTA concepts and technologies were used and are thus being evaluated in the field: The upgraded read-out electronics is based on the NECTAR readout chips; the new camera front- and back-end control subsystems are based on an FPGA and an embedded ARM computer; the communication between subsystems is based on standard Ethernet technologies. These hardware solutions offer good performance, robustness and flexibility. The design of the new cameras is reported here.Comment: Proceedings of the 34th International Cosmic Ray Conference, 30 July- 6 August, 2015, The Hague, The Netherland

Analyzing collaborative learning processes automatically

In this article we describe the emerging area of text classification research focused on the problem of collaborative learning process analysis both from a broad perspective and more specifically in terms of a publicly available tool set called TagHelper tools. Analyzing the variety of pedagogically valuable facets of learners’ interactions is a time consuming and effortful process. Improving automated analyses of such highly valued processes of collaborative learning by adapting and applying recent text classification technologies would make it a less arduous task to obtain insights from corpus data. This endeavor also holds the potential for enabling substantially improved on-line instruction both by providing teachers and facilitators with reports about the groups they are moderating and by triggering context sensitive collaborative learning support on an as-needed basis. In this article, we report on an interdisciplinary research project, which has been investigating the effectiveness of applying text classification technology to a large CSCL corpus that has been analyzed by human coders using a theory-based multidimensional coding scheme. We report promising results and include an in-depth discussion of important issues such as reliability, validity, and efficiency that should be considered when deciding on the appropriateness of adopting a new technology such as TagHelper tools. One major technical contribution of this work is a demonstration that an important piece of the work towards making text classification technology effective for this purpose is designing and building linguistic pattern detectors, otherwise known as features, that can be extracted reliably from texts and that have high predictive power for the categories of discourse actions that the CSCL community is interested in

Aging Studies for the Large Honeycomb Drift Tube System of the Outer Tracker of HERA-B

The HERA-B Outer Tracker consists of drift tubes folded from polycarbonate foil and is operated with Ar/CF4/CO2 as drift gas. The detector has to stand radiation levels which are similar to LHC conditions. The first prototypes exposed to radiation in HERA-B suffered severe radiation damage due to the development of self-sustaining currents (Malter effect). In a subsequent extended R&D program major changes to the original concept for the drift tubes (surface conductivity, drift gas, production materials) have been developed and validated for use in harsh radiation environments. In the test program various aging effects (like Malter currents, gain loss due to anode aging and etching of the anode gold surface) have been observed and cures by tuning of operation parameters have been developed.Comment: 14 pages, 6 figures, to be published in the Proceedings of the International Workshop On Aging Phenomena In Gaseous Detectors, 2-5 Oct 2001, Hamburg, German

Isolation of human intrahepatic leukocytes for phenotypic and functional characterization by flow cytometry

With the growing appreciation of tissue-resident immunity, studying tissue-specific immune cells contributing to both homeostasis and disease is imperative. Here, we provide a protocol for the isolation of human intrahepatic leukocytes (IHL) maximizing viability, purity, and yield. Our protocol is scalable by tissue weight, allowing for reproducible and efficient IHL liberation suitable for functional characterization, cell isolation, and profiling by flow (or mass) cytometry. Furthermore, we provide a "guide" to determine an expected IHL yield per gram of tissue processed. For complete details on the use and execution of this protocol, please refer to Stegmann et al. (2016), Pallett et al. (2017), Easom et al. (2018), Swadling et al. (2020), Pallett et al. (2020), and Zakeri et al. (2022)

The Outer Tracker Detector of the HERA-B Experiment. Part II: Front-End Electronics

The HERA-B Outer Tracker is a large detector with 112674 drift chamber channels. It is exposed to a particle flux of up to 2x10^5/cm^2/s thus coping with conditions similar to those expected for the LHC experiments. The front-end readout system, based on the ASD-8 chip and a customized TDC chip, is designed to fulfil the requirements on low noise, high sensitivity, rate tolerance, and high integration density. The TDC system is based on an ASIC which digitizes the time in bins of about 0.5 ns within a total of 256 bins. The chip also comprises a pipeline to store data from 128 events which is required for a deadtime-free trigger and data acquisition system. We report on the development, installation, and commissioning of the front-end electronics, including the grounding and noise suppression schemes, and discuss its performance in the HERA-B experiment

The Outer Tracker Detector of the HERA-B Experiment Part I: Detector

The HERA-B Outer Tracker is a large system of planar drift chambers with about 113000 read-out channels. Its inner part has been designed to be exposed to a particle flux of up to 2.10^5 cm^-2 s^-1, thus coping with conditions similar to those expected for future hadron collider experiments. 13 superlayers, each consisting of two individual chambers, have been assembled and installed in the experiment. The stereo layers inside each chamber are composed of honeycomb drift tube modules with 5 and 10 mm diameter cells. Chamber aging is prevented by coating the cathode foils with thin layers of copper and gold, together with a proper drift gas choice. Longitudinal wire segmentation is used to limit the occupancy in the most irradiated detector regions to about 20 %. The production of 978 modules was distributed among six different laboratories and took 15 months. For all materials in the fiducial region of the detector good compromises of stability versus thickness were found. A closed-loop gas system supplies the Ar/CF4/CO2 gas mixture to all chambers. The successful operation of the HERA-B Outer Tracker shows that a large tracker can be efficiently built and safely operated under huge radiation load at a hadron collider.Comment: 28 pages, 14 figure

First detection of a VHE gamma-ray spectral maximum from a Cosmic source: H.E.S.S. discovery of the Vela X nebula

The Vela supernova remnant (SNR) is a complex region containing a number of sources of non-thermal radiation. The inner section of this SNR, within 2 degrees of the pulsar PSR B0833-45, has been observed by the H.E.S.S. gamma-ray atmospheric Cherenkov detector in 2004 and 2005. A strong signal is seen from an extended region to the south of the pulsar, within an integration region of radius 0.8 deg. around the position (RA = 08h 35m 00s, dec = -45 deg. 36' J2000.0). The excess coincides with a region of hard X-ray emission seen by the ROSAT and ASCA satellites. The observed energy spectrum of the source between 550 GeV and 65 TeV is well fit by a power law function with photon index = 1.45 +/- 0.09(stat) +/- 0.2(sys) and an exponential cutoff at an energy of 13.8 +/- 2.3(stat) +/- 4.1(sys) TeV. The integral flux above 1 TeV is (1.28 +/- 0.17 (stat) +/- 0.38(sys)) x 10^{-11} cm^{-2} s^{-1}. This result is the first clear measurement of a peak in the spectral energy distribution from a VHE gamma-ray source, likely related to inverse Compton emission. A fit of an Inverse Compton model to the H.E.S.S. spectral energy distribution gives a total energy in non-thermal electrons of ~2 x 10^{45} erg between 5 TeV and 100 TeV, assuming a distance of 290 parsec to the pulsar. The best fit electron power law index is 2.0, with a spectral break at 67 TeV.Comment: 5 pages, 4 figures, accepted for publication in Astronomy and Astrophysics letter

3.9 day orbital modulation in the TeV gamma-ray flux and spectrum from the X-ray binary LS 5039

New observations of LS 5039, a High Mass X-ray Binary comprising a massive star and compact object, were carried out with the High Energy Stereoscopic System of Cherenkov Telescopes (H.E.S.S.) in 2005 at very high energy (VHE) gamma-ray energies. These observations reveal that its flux and energy spectrum are modulated with the 3.9 day orbital period of the binary system. This is the first time in gamma-ray astronomy that orbital modulation has been observed, and periodicity clearly established using ground-based gamma-ray detectors. The VHE gamma-ray emission is largely confined to half of the orbit, peaking around the inferior conjunction epoch of the compact object. For this epoch, there is also a hardening of the energy spectrum in the energy range between 0.2 TeV and a few TeV. The flux vs. orbital phase profile provides the first clear indication of gamma-ray absorption via pair production within an astrophysical source, a process which is expected to occur if the gamma-ray production site is situated within ~1 AU of the compact object. Moreover the production region size must be not significantly greater than the binary separation (~0.15 AU). Notably, these constraints are also considerably smaller than the collimated outflows or jets (extending out to ~1000 AU) observed in LS 5039. The spectral hardening could arise from variations with phase in the maximum electron energies, and/or the dominant VHE gamma-ray production mechanism.Comment: 8 pages, 8 figures, accepted for publication in Astronomy & Astrophysic

The matrix metalloproteinase ADAM10 supports hepatitis C virus entry and cell-to-cell spread via its sheddase activity

Hepatitis C virus (HCV) exploits the four entry factors CD81, scavenger receptor class B type I (SR-BI, also known as SCARB1), occludin, and claudin-1 as well as the co-factor epidermal growth factor receptor (EGFR) to infect human hepatocytes. Here, we report that the disintegrin and matrix metalloproteinase 10 (ADAM10) associates with CD81, SR-BI, and EGFR and acts as HCV host factor. Pharmacological inhibition, siRNA-mediated silencing and genetic ablation of ADAM10 reduced HCV infection. ADAM10 was dispensable for HCV replication but supported HCV entry and cell-to-cell spread. Substrates of the ADAM10 sheddase including epidermal growth factor (EGF) and E-cadherin, which activate EGFR family members, rescued HCV infection of ADAM10 knockout cells. ADAM10 did not influence infection with other enveloped RNA viruses such as alphaviruses and a common cold coronavirus. Collectively, our study reveals a critical role for the sheddase ADAM10 as a HCV host factor, contributing to EGFR family member transactivation and as a consequence to HCV uptake