Gastrointestinal stromal tumors (GISTs): Point mutations matter in management, a review

The therapeutic implications of the genomic alterations seen within the drivers of gastrointestinal stromal tumors (GIST) are among the best understood in all of solid tumors. Sequencing of cKIT and PDGFRα should be considered standard practice for the treatment of GIST patients. In this article, we will review the common mutations and how they are utilized in clinical management. In addition, we will review the rare D842V PDGFRα mutation and the diverse molecular group that lacks a mutation in either cKIT or PDGFRα (wild-type GIST) which are best treated on clinical trial. Finally, we will look forward at the future therapies that are ever evolving for management of GIST. Taken together, the scientific advances in understanding the molecular basis of GIST validates the importance of knowing and understanding the mutations that are present in any one patient

Can GPR4 be a potential therapeutic target for COVID-19?

This study was supported in part by the North Carolina COVID-19 Special State Appropriations. Research in the author's laboratory was also supported by a grant from the National Institutes of Health (R15DK109484, to LY).Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first emerged in late 2019 and has since rapidly become a global pandemic. SARS-CoV-2 infection causes damages to the lung and other organs. The clinical manifestations of COVID-19 range widely from asymptomatic infection, mild respiratory illness to severe pneumonia with respiratory failure and death. Autopsy studies demonstrate that diffuse alveolar damage, inflammatory cell infiltration, edema, proteinaceous exudates, and vascular thromboembolism in the lung as well as extrapulmonary injuries in other organs represent key pathological findings. Herein, we hypothesize that GPR4 plays an integral role in COVID-19 pathophysiology and is a potential therapeutic target for the treatment of COVID-19. GPR4 is a pro-inflammatory G protein-coupled receptor (GPCR) highly expressed in vascular endothelial cells and serves as a “gatekeeper� to regulate endothelium-blood cell interaction and leukocyte infiltration. GPR4 also regulates vascular permeability and tissue edema under inflammatory conditions. Therefore, we hypothesize that GPR4 antagonism can potentially be exploited to mitigate the hyper-inflammatory response, vessel hyper-permeability, pulmonary edema, exudate formation, vascular thromboembolism and tissue injury associated with COVID-19.ECU Open Access Publishing Support Fun

Empirical comparison of high gradient achievement for different metals in DC and pulsed mode

For the SwissFEL project, an advanced high gradient low emittance gun is under development. Reliable operation with an electric field, preferably above 125 MV/m at a 4 mm gap, in the presence of an UV laser beam, has to be achieved in a diode configuration in order to minimize the emittance dilution due to space charge effects. In the first phase, a DC breakdown test stand was used to test different metals with different preparation methods at voltages up to 100 kV. In addition high gradient stability tests were also carried out over several days in order to prove reliable spark-free operation with a minimum dark current. In the second phase, electrodes with selected materials were installed in the 250 ns FWHM, 500 kV electron gun and tested for high gradient breakdown and for quantum efficiency using an ultra-violet laser.Comment: 25 pages, 13 figures, 5 tables. Follow up from FEL 2008 conference (Geyongju Korea 2008) New Title in JVST A (2010) : Vacuum breakdown limit and quantum efficiency obtained for various technical metals using DC and pulsed voltage source

Towards a New Science of a Clinical Data Intelligence

In this paper we define Clinical Data Intelligence as the analysis of data generated in the clinical routine with the goal of improving patient care. We define a science of a Clinical Data Intelligence as a data analysis that permits the derivation of scientific, i.e., generalizable and reliable results. We argue that a science of a Clinical Data Intelligence is sensible in the context of a Big Data analysis, i.e., with data from many patients and with complete patient information. We discuss that Clinical Data Intelligence requires the joint efforts of knowledge engineering, information extraction (from textual and other unstructured data), and statistics and statistical machine learning. We describe some of our main results as conjectures and relate them to a recently funded research project involving two major German university hospitals.Comment: NIPS 2013 Workshop: Machine Learning for Clinical Data Analysis and Healthcare, 201

Studies on charge production from Cs2Te photocathodes in the PITZ L-band normal conducting radio frequency photo injector

This paper discusses the behavior of electron bunch charge produced in an L-band normal conducting radio frequency cavity (RF gun) from Cs2Te photocathodes illuminated with ps-long UV laser pulses when the laser transverse distribution consists of a flat-top core with Gaussian-like decaying halo. The produced charge shows a linear dependence at low laser pulse energies as expected in the quantum efficiency limited emission regime, while its dependence on laser pulse energy is observed to be much weaker for higher values, due to space charge limited emission. However, direct plug-in of experimental parameters into the space charge tracking code ASTRA yields lower output charge in the space charge limited regime compared to measured values. The rate of increase of the produced charge at high laser pulse energies close to the space charge limited emission regime seems to be proportional to the amount of halo present in the radial laser profile since the charge from the core has saturated already. By utilizing core + halo particle distributions based on measured radial laser profiles, ASTRA simulations and semi-analytical emission models reproduce the behavior of the measured charge for a wide range of RF gun and laser operational parameters within the measurement uncertainties.Comment: 15 pages, 16 figures, 2 table

Photocathode laser based bunch shaping for high transformer ratio plasma wakefield acceleration

Beam driven plasma acceleration is one of the most promising candidates for future compact particle accelerator technologies. In this scheme a particle bunch drives a wake in a plasma medium. The fields inside of the wake can be used to accelerate a trailing witness bunch. To maximise the ratio between acceleration of the witness to deceleration of the drive bunch, the so called transformer ratio, several methods have been proposed. The ones yielding the most favorable results are based on shaped drive bunches that are long in terms of the plasma wavelength. We present here methods to create such drive bunches employing temporally shaped UV-laser pulses for the extraction of electron bunches from a photo-electron gun. Theoretical considerations, experimental results and possibilities for further improvements are discussed

Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

BACKGROUND: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. METHODS: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. RESULTS: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. CONCLUSIONS: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years