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The project OPTIMAP is at the current stage a joint initiative of BGIC, GSSAC and DGFI-TUM. The development of an operational tool for ionospheric mapping and prediction is the main goal of the project.The ionosphere is a dispersive medium. Therefore, GNSS signals are refracted while they pass through the ionosphere. The magnitude of the refraction rate depends on the frequencies of the transmitted GNSS signals. The ionospheric disturbance on the GNSS signals paves the way of extracting Vertical Total Electron Content (VTEC) information of the ionosphere.In OPTIMAP, the representation of the global and regional VTEC signal is based on localizing B-spline basis functions. For global VTEC modeling, polynomial B-splines are employed to represent the latitudinal variations, whereas trigonometric B-splines are used for the longitudinal variations. The regional modeling in OPTIMAP relies on a polynomial B-spline representation for both latitude and longitude.The VTEC modeling in this study relies on both a global and a regional sequential estimator (Kalman filter) running in a parallel mode. The global VTEC estimator produces VTEC maps based on data from GNSS receiver stations which are mainly part of the global real-time IGS network. The global estimator relies on additional VTEC information obtained from a forecast procedure using ultra-rapid VTEC products. The regional estimator makes use of the VTEC product of the real-time global estimator as background information and generates high-resolution VTEC maps using real-time data from the EUREF Permanent GNSS Network. EUREF provides a network of very dense GNSS receivers distributed alongside Europe.Carrier phase observations acquired from GPS and GLONASS, which are transmitted in accordance with RTCM standard, are used for real-time regional VTEC modeling. After the acquisition of GNSS data, cycle slips for each satellite-receiver pair are detected, and ionosphere observations are constructed via the linear combination of carrier-phase observations in the data pre-processing step. The unknown B-spline coefficients, as well as the biases for each phase-continuous arc belonging to each receiver-satellite pair, are simultaneously estimated in the Kalman filter.Within this study, we compare the performance of regional and global VTEC products generated in real-time using the well-known dSTEC analysis.

The project OPTIMAP is at the current stage a joint initiative of BGIC, GSSAC and DGFI-TUM. The development of an operational tool for ionospheric mapping and prediction is the main goal of the project.The ionosphere is a dispersive medium. Therefore, GNSS signals are refracted while they pass through the ionosphere. The magnitude of the refraction rate depends on the frequencies of the transmitted GNSS signals. The ionospheric disturbance on the GNSS signals paves the way of extracting Vertical Total Electron Content (VTEC) information of the ionosphere.In OPTIMAP, the representation of the global and regional VTEC signal is based on localizing B-spline basis functions. For global VTEC modeling, polynomial B-splines are employed to represent the latitudinal variations, whereas trigonometric B-splines are used for the longitudinal variations. The regional modeling in OPTIMAP relies on a polynomial B-spline representation for both latitude and longitude.The VTEC modeling in this study relies on both a global and a regional sequential estimator (Kalman filter) running in a parallel mode. The global VTEC estimator produces VTEC maps based on data from GNSS receiver stations which are mainly part of the global real-time IGS network. The global estimator relies on additional VTEC information obtained from a forecast procedure using ultra-rapid VTEC products. The regional estimator makes use of the VTEC product of the real-time global estimator as background information and generates high-resolution VTEC maps using real-time data from the EUREF Permanent GNSS Network. EUREF provides a network of very dense GNSS receivers distributed alongside Europe.Carrier phase observations acquired from GPS, GLONASS and GALILEO constellations, which are transmitted in accordance with RTCM standard, are used for real-time regional VTEC modeling. After the acquisition of GNSS data, cycle slips for each satellite-receiver pair are detected, and ionosphere observations are constructed via the linear combination of carrier-phase observations in the data pre-processing step. The unknown B-spline coefficients, as well as the biases for each phase-continuous arc belonging to each receiver-satellite pair, are simultaneously estimated in the Kalman filter.Within this study, we compare the performance of regional and global VTEC products generated in real-time using the well-known dSTEC analysis.

Background: Chemoimmunotherapy is typically the standard of care for patients with Waldenström macroglobulinemia; however, infectious and hematologic toxic effects are problematic. Acalabrutinib is a selective, potent Bruton tyrosine-kinase inhibitor. The aim of this trial was to evaluate the activity and safety of acalabrutinib in patients with Waldenström macroglobulinemia. Methods: This single-arm, multicentre, phase 2 trial was done in 19 European academic centres in France, Italy, Greece, the Netherlands, and the UK, and eight academic centres in the USA. Eligible patients were 18 years or older and had treatment naive (declined or not eligible for chemoimmunotherapy) or relapsed or refractory (at least one previous therapy) Waldenström macroglobulinemia that required treatment, an Eastern Cooperative Oncology Group performance status of 2 or less, and received no previous Bruton tyrosine-kinase inhibitor therapy. Patients received 100 mg oral acalabrutinib twice per day in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed overall response (at least a minor response) according to the 6th International Workshop for Waldenström Macroglobulinemia (IWWM) and the modified 3rd IWWM workshop criteria. The primary outcome and safety were assessed in all patients who received at least one dose of treatment. This study is registered with ClinicalTrials.gov, number NCT02180724, and is ongoing, but no longer enrolling. Findings: Between Sept 8, 2014, and Dec 24, 2015, 122 patients were assessed for eligibility, of which 106 (87%) patients were given acalabrutinib (14 were treatment naive and 92 had relapsed or refractory disease). With a median follow-up of 27·4 months (IQR 26·0–29·7), 13 (93% [95% CI 66–100]) of 14 treatment naive patients achieved an overall response and 86 (93% [86–98]) of 92 relapsed or refractory patients per both the modified 3rd and 6th IWWM criteria. Seven (50%) of 14 treatment naive patients and 23 (25%) of 92 relapsed or refractory patients discontinued treatment on study. Grade 3–4 adverse events occurring in more than 5% of patients were neutropenia (17 [16%] of 106 patients) and pneumonia (7 [7%]). Grade 3–4 atrial fibrillation occurred in one (1%) patient and grade 3–4 bleeding occurred in three (3%) patients. The most common serious adverse events were lower respiratory tract infection (n=7 [7%]), pneumonia (n=7 [7%]), pyrexia (n=4 [4%]), cellulitis (n=3 [3%]), fall (n=3 [3%]), and sepsis (n=3 [3%]). Pneumonia (n=5 [5%]) and lower respiratory tract infection (n=4 [4%]) were considered treatment related. One treatment-related death was reported (intracranial hematoma). Interpretation: This study provides evidence that acalabrutinib is active as single-agent therapy with a manageable safety profile in patients with treatment-naive, or relapse or refractory Waldenström macroglobulinemia. Further studies are needed to establish its efficacy against current standard treatments and to investigate whether outcomes can be improved with combination therapies. Funding: Acerta Pharma. © 2020 Elsevier Ltd

Einleitung: In der Literatur findet man zunehmend Berichte uber die Unvollstandigkeit der arztlichen Aufklarungen durch „Residents“. Diese fuhlen sich wiederum unsicher und nicht adaquat auf diese Aufgabe vorbereitet. Ziel dieses Projekts war es, die Aufklarung von Patienten in die studentische Ausbildung unter kontrollierten Bedingungen zu integrieren, anstatt dies nur im Rollenspiel mit Kommilitonen oder Schauspielpatienten zu uben. Methoden: An der Universitat Magdeburg wurde vor Kurzem die neue Unterrichtseinheit „STeP“ („Students Teaching Patients“) fur Medizinstudierende eingefuhrt. Die Medizinstudierenden werden zunachst von einem approbierten Arzt auf die arztliche Aufklarung vorbereitet. Sie fuhren nach adaquater Einfuhrung beim bereits arztlich aufgeklarten Patienten eine strukturierte Abfrage der Aufklarungsinhalte durch. Im Rahmen der Nachbereitung berichten sie dem Arzt uber das stattgefundene Gesprach. Schlieslich vergewissert sich der Arzt im 4-Augen-Gesprach mit dem Patienten daruber, dass keine Unsicherheiten entstanden sind. In Erweiterung zum ursprunglichen Ablauf wurde im vorliegenden Teilprojekt die studentische Abfrage 2-mal am gleichen Patienten durchgefuhrt, um die Wissenszunahme der Patienten durch das studentische Gesprach zu untersuchen. Ergebnisse: Trotz absolviertem Chirurgiekurs ist es den Medizinstudierenden nicht hinreichend klar, welche Komplikationen im Rahmen der laparoskopischen Cholezystektomie eine hohe Relevanz aufweisen. Ahnlich schwierig war es auch fur Patienten, die bereits arztlich aufgeklart worden waren, wiederzugeben, welche Folgen und Komplikationen aus diesem Eingriff entstehen konnen. So konnte eine Stichprobe von Patienten bspw. nach erfolgter arztlicher Aufklarung durchschnittlich nur eine einzige Komplikation in der STeP-Abfrage wiedergeben, und nur ein kleiner Anteil konnte sich unter der „Verletzung des Ductus hepatocholedochus“ etwas vorstellen. Die Anzahl an Komplikationen, die von den 10 Patienten in der 2. STeP-Abfrage benannt werden konnte, stieg. Die generelle Bereitschaft der Patienten, das Gesprach 2-mal durchzufuhren, sank allerdings und fuhrte in der Folge zum Abbruch dieses Teilprojekts. Schlussfolgerung: Die Analyse der Limitationen der hier beschriebenen methodischen Veranderung (Zweitbefragung) resultiert in einer Weiterentwicklung der Methodik von STeP: Das studentische Gesprach soll nun vor der arztlichen Aufklarung im Sinne eines „Beratungsgesprachs“ stattfinden und vom Studierenden in Form einer Selbstreflexion evaluiert werden. Die Auswertung von Wissenszuwachs und Zufriedenheit der Patienten erfolgt dann durch die Studierenden – allerdings erst postoperativ. Die Ergebnisse dieser veranderten Masnahme stehen zurzeit noch aus.

The source of continental rift-related basalts and their relation to rifting processes is a continuous matter of debate. We present major and trace element and Sr, Nd, Hf and Pb isotope data for axial rift basalts from eight volcanic centres (Ayelu, Hertali, Dofan, Fantale, Kone, Bosetti and Gedemsa, from NE to SW) in Afar and Main Ethiopian Rift (MER) to assess their source regions and their genetic relationships. These lavas have geochemical characteristics, i.e., a peak at Ba, Nb and troughs at K and Rb in primitive mantle-normalised multielement diagrams, which are consistent with predominant melting of an amphibole-bearing lithospheric mantle. However, the isotopic compositions for these lavas are heterogeneous (Sr-87/Sr-86 = 0.70354-0.70431, Nd-143/Nd-144 = 0.51280-0.51294,(176)Hr/Hf-177 = 0.28301-0.28315, Pb-206/Pb-204 = 18.48-19.31, Pb-207/Pb-204 = 15.53-15.62, Pb-208/Pb-204 = 38.61-39.06) and require various mantle reservoirs with distinctive isotopic signatures. The range of isotopic compositions requires the involvement of three distinct source components from the asthenospheric and veined lithospheric mantle. Progressive rifting leads to lithosperic thinning and upwelling of hot asthenospheric mantle, which induces melting of the veined lithospheric mantle. The trace element characteristics of the lavas are dominated by the vein material, which has a higher trace element content than the surrounding mantle. The isotopic composition of the vein material, however, is not very different from the ambient mantle, giving rise of apparent uncoupling of trace element and isotope constraints for the melt source. The uprising basaltic liquids in part inherit a lithospheric trace element signature, while their isotopic compositions are mostly unaffected due to short residence times within the lithosphere in context with progressive rifting and lithospheric thinning. Thus, the geochemical and isotope data are consistent with a multi-component source prevailing beneath the Afar and MER areas in which the basalts are generated during progressive rifting and, thus, passive upwelling of a mantle source. (C) 2016 The Authors. Published by Elsevier B.V.

Several prognostic indices (PI) have been developed to stratify patients with brain metastases in groups with good or bad prognosis. The aim of our study was to compare nine prognostic scores for patients with brain metastases (BM) of breast cancer receiving radiotherapy. The clinical data of 139 breast cancer patients with BM were collected retrospectively. All patients were treated with cerebral radiotherapy or surgery followed by radiotherapy between January 2007 and December 2012. The prognostic value and accuracy of recursive partitioning analysis (RPA), RPA II, graded prognostic assessment (GPA), basic score for BM, Breast-RPA, Breast-GPA, Rades Score 2011, Germany Score and Breast Rades Score were assessed. The median survival after BM diagnosis in our cohort was 14 months. The overall 6-month, 1-, 2- and 3-year survival rates were 49.6, 37.4, 20.9 and 13.7 %, respectively. Most of the PI were associated with OS, but univariate analysis favored GPA regarding OS. GPA was the most accurate score to identify patients with long (longer than 12 months) and Breast-GPA patients with short (

The HAWAI registry evaluated the role of heart rate variability in predicting the occurrence of ventricular tachycardia and fibrillation (VT/VF) and sinus tachycardia in patients with an implantable cardioverter-defibrillator (45 patients with 155 RR recordings). A significant decrease of the mean value of all RR intervals (MeanNN) was observed in the period starting 20 and 40 min prior to VT/VF and sinus tachycardia, respectively. The standard deviation of RR intervals (SDNN) and the power at low frequency (LF) were the only parameters with significant changes prior to VT/VF. For sinus tachycardia, the root mean square of successive differences of all successive RR intervals (r-MSSD) and the power at low and high frequency (HF) decreased, whereas SDNN and the power at very low frequency increased. Comparison of RR recordings preceding VT/VF and sinus tachycardia revealed significant differences of the MeanNN, SDNN, r-MSSD, LF and HF. Based on a classification and regression tree analysis, MeanNN, SDNN and r-MSSD showed a sensitivity of 94.4% and a specificity of 50.6% as predictors of VT/VF. Our results suggest that the temporal changes in heart rate before an arrhythmic event can be used to predict the occurrence of VT/VF. These parameters may be used to optimize pacing therapies designed to prevent VT/VF recurrences as well as for improving device-based discriminators for VT/VF and sinus tachycardia.

We expand upon the recent semi-stochastic adaptation to full configuration interaction quantum Monte Carlo (FCIQMC). We present an alternate method for generating the deterministic space without a priori knowledge of the wave function and present stochastic efficiencies for a variety of both molecular and lattice systems. The algorithmic details of an efficient semi-stochastic implementation are presented, with particular consideration given to the effect that the adaptation has on parallel performance in FCIQMC. We further demonstrate the benefit for calculation of reduced density matrices in FCIQMC through replica sampling, where the semi-stochastic adaptation seems to have even larger efficiency gains. We then combine these ideas to produce explicitly correlated corrected FCIQMC energies for the Beryllium dimer, for which stochastic errors on the order of wavenumber accuracy are achievable., 10 pages, 7 figures

A photogrammetric survey of a unique archaeological site is reported in this paper. The survey was performed using both a panoramic image-based solution and by classical procedure. The panoramic image-based solution was carried out employing a commercial solution: the Trimble V10 Imaging Rover (IR). Such instrument is an integrated cameras system that captures 360 degrees digital panoramas, composed of 12 images, with a single push. The direct comparison of the point clouds obtained with traditional photogrammetric procedure and V10 stations, using the same GCP coordinates has been carried out in Cloud Compare, open source software that can provide the comparison between two point clouds supplied by all the main statistical data. The site is a portion of the dial plate of the “Horologium Augusti” inaugurated in 9 B.C.E. in the area of Campo Marzio and still present intact in the same position, in a cellar of a building in Rome, around 7 meter below the present ground level.