The temporal cell surface expression of lymphocyte activated gene 3 (LAG3) on recently activated T cells presents an opportunity for targeted therapy in certain inflammatory diseases. LAG3+ cells are enriched in inflamed lesions in ulcerative colitis,1 Crohn’s disease and psoriasis. GSK2831781 is a highly potent, humanised IgG1, antibody-dependent cellular cytotoxicity-enhanced monoclonal antibody that depletes LAG3+ cells. A single escalating intravenous dose of GSK2831781 or placebo was administered to 40 healthy volunteers (up to 0.15 mg/kg). Three cohorts of nine patients with mild–moderate psoriasis were randomised to GSK2831781 (0.5, 1.5, or 5 mg/kg) or placebo in a 2:1 ratio. Safety, tolerability, pharmacokinetics (PK), and immunogenicity were evaluated. Circulating LAG3+ T cells were quantified using flow cytometry. LAG3+ and CD3+ cell counts and transcriptomics were assessed in psoriatic skin biopsies acquired prior to dosing and at Day 29. Psoriasis activity severity indices (PASI) and plaque lesion severity scores (PLSS) were profiled. GSK2831781 was well-tolerated with no safety concerns identified. PK was non-linear, partly explained by target-mediated drug disposition; the non-linear process was saturated at doses ≥0.5 mg/kg. Dose-dependent depletion of circulating LAG3+ memory T cells was observed for 6–8 weeks following a single 5 mg/kg dose. LAG3+ and CD3+ (Figure 1) cells were reduced in psoriasis skin biopsies at 1.5 and 5 mg/kg. Preliminary analysis showed down-regulation of pro-inflammatory mRNA transcripts (IL-17F, IFN-γ, and S100A12) and up-regulation of those associated with epithelial integrity (CDHR1) which met the threshold of ≥1.5-fold change in median values vs. placebo at 5 mg/kg. There was no apparent decrease to Treg-associated transcripts (IL-10 and FOXP3). GSK2831781 improved PASI and PLSS (Figure 1) at all doses (difference of estimated mean change from baseline in PLSS vs. placebo for 5 mg/kg, on Day 29 was −2.01 [95% CI: −3.57, −0.44]). The per cent change from baseline PLSS mean for 5 mg/kg, Day 29 was −30.9% (SD: 13.41) vs. placebo −1.9% (SD: 22.40). Figure 1 GSK2831781 effected dose-dependent depletion of LAG3+ T cells in blood, reduced LAG3+ and CD3+ cells in psoriatic skin and exhibited encouraging effects on pro-inflammatory and epithelial integrity transcripts, which translated into clinical improvements. These data are supportive of Phase II studies in other T-cell-related diseases, including inflammatory bowel disease. Reference 1. Slevin S, Tan M, Lahiff C, et al. Intestinal expression of LAG-3 correlates with inflammatory activity and response to biological therapy in ulcerative colitis. J Crohn’s Colitis 2018;S125. doi:10.1093/ecco-jcc/jjx180.191

The demand for accurate solar irradiance nowcast increases together with the rapidly growing share of solar energy within our electricity grids. Intra-hour variabilities, mainly caused by clouds, have a significant impact on solar power plant dispatch and thus on electricity grids. All sky imager (ASI) based nowcasting systems, with a high temporal and spatial resolution, can provide irradiance nowcasts that can help to optimize CSP plant operation, solar power plant dispatch and grid operation. The radiative effect of clouds is highly variable and depends on micro- and macrophysical cloud properties. Frequently, nowcasting systems have to measure/estimate the radiative effect during complex multi-layer conditions with strong variations of the optical properties between individual clouds. We present a novel approach determining cloud transmittance from measurements or from correlations of transmittance with cloud height information. The cloud transmittance is measured by a pyrheliometer when shaded, as the ratio of shaded direct normal irradiance (DNI) and clear sky DNI. However, for most clouds, direct transmittance measurements are not available, as these clouds are not shading the used pyrheliometers. These clouds receive an estimated transmittance value based on (1) their height, (2) results of a probability analysis with historical cloud height and transmittance measurements as well as (3) recent transmittance measurements and their corresponding cloud height. Cloud heights are measured by a stereoscopic approach utilizing two ASIs. We discuss site dependencies of the presented transmittance estimation method and the potential integration of automatic cloud classification approaches. We validated the cloud transmittance estimation over two years (2016 and 2017) and compare the probabilistic cloud transmittance estimation approach with four simple approaches. The overall mean-absolute deviation (MAD) and root-mean-square deviation (RMSD) are 0.11 and 0.16 respectively for transmittance. The deviations are significantly lower for optically thick or thin clouds and larger for clouds with moderate transmittance between 0.18 and 0.585. Furthermore we validated the overall DNI forecast quality of the entire nowcasting system, using this transmittance estimation method, over the same data set with three spatially distributed pyrheliometers. Overall deviations of 13% and 21% are reached for the relative MAD and RMSD with a lead time of 10 min. The effects of the chosen data set on the validation results are demonstrated by means of the skill score.

All-sky imager based systems can be used to measure a number of cloud properties. Configurations consisting of two all-sky imagers can be used to derive cloud heights for weather stations, aviation and nowcasting of solar irradiance. One key question for such systems is the optimal distance between the all-sky imagers. This problem has not been studied conclusively in the literature. To the best of our knowledge, no previous in-field study of the optimal camera distance was performed. Also, comprehensive modeling is lacking. Here, we address this question with an in-field study on 93 days using 7 camera distances between 494 m and 2562 m and one specific cloud height estimation approach. We model the findings and draw conclusions for various configurations with different algorithmic methods and camera hardware. The camera distance is found to have a major impact on the accuracy of cloud height determinations. For the used 3 megapixel cameras, cloud heights up to 12,000 m and the used algorithmic approaches, an optimal camera distance of approximately 1500 m is determined. Optimal camera distances can be reduced to less than 1000 m if higher camera resolutions (e.g. 6 megapixel) are deployed. A step-by-step guide to determine the optimal camera distance is provided.

Die Sichtung ist eine grundlegende ärztliche Maßnahme der Lageerkundung beim Massenanfall von Verletzten (MANV). In der frühen Einsatzphase kann eine Vorsichtung durch geeignetes, nichtärztliches Rettungsdienstpersonal sinnvoll sein, um einen raschen Lageüberblick zu erhalten, weil der ersteintreffende Notarzt oder Leitende Notarzt im Rahmen seiner Leitungsfunktion zunächst eine Grundordnung an der Einsatzstelle herstellen muss. Es wird über ein Projekt zur Erarbeitung eines Vorsichtungskonzepts im Rettungsdienstbereich Amberg (Bayern) berichtet. In einem informellen Gruppenprozess wurden Zieldefinitionen für das Konzept erarbeitet, ein Vorsichtungsalgorithmus samt Sichtungskennzeichnung entwickelt, und dieser in ein Gesamtkonzept für die erste Einsatzphase eingebettet. Zuletzt wurden Festlegungen zur Ausbildung, Zertifizierung und Implementierung getroffen. Der Amberg-Schwandorf-Algorithmus für die Vorsichtung (ASAV) ist im Vergleich zu dem überregional bekannten mSTaRT-Algorithmus verkürzt. Die beiden mSTaRT-Elemente zur Atmung wurden zu einem Punkt „Atemstörung?“ zusammengefasst. Eine weitere Modifikation betrifft die Blutstillung. Die Sichtungskennzeichnung erfolgt mit farbigen Plastikbändern. Ein Algorithmus für die Frühphase eines MANV-Einsatzes beschreibt das Vorgehen durch die ersteintreffende rettungsdienstliche Fahrzeugbesatzung. Zur Durchführung der Vorsichtung ist eine strukturierte Ausbildung sowie das Absolvieren einer praktischen Prüfung erforderlich. Das Amberg-Schwandorf-Konzept schließt die Lücke der frühen Einsatzphase bei bisherigen MANV-Konzepten. Der zugrunde liegende Algorithmus geht im Gegensatz zu mSTaRT mit den Anforderungen der nationalen Sichtungs-Konsensus-Konferenzen konform. Als Limitation ist zu formulieren, dass die Güte der Vorsichtung in weiteren Untersuchungen verifiziert werden muss.

In case of mass casualty incidents (MCI), in German emergency medical services (EMS) systems prehospital triage lies within the responsibility of emergency physicians. In case that there are not enough physicians available to complete triage in a timely fashion, a preliminary medical survey by ambulance personnel (sweeping triage) is indicated. We report the development of a regionally adapted, comprehensive concept for sweeping triage by non-physician EMS personnel. A project team agreed on a triage algorithm, triage labeling, and a strategic concept for the early MCI mission phase. Consecutively, determinations for education, certification, and implementation were made. The Amberg-Schwandorf algorithm for sweeping triage (ASAV) was based on the mSTaRT triage algorithm. By merging the two mSTaRT elements on respiration to a single element named "breathing disorders?", the algorithm was slightly simplified. Additionally, the bleeding control element was modified. Labeling of patients according to triage results is accomplished by colored plastic ribbons. A newly defined algorithm describes the early scene management by the first arriving EMS team. Education of the concept consists of a 3 hour lecture and 1 hour of practical training, followed by a practical exam. A renewal of the certificate is necessary after 3 years. The Amberg-Schwandorf concept fills a gap concerning the early mission phase in existing MCI algorithms. In contrast to mSTaRT, the concept is in agreement with the requirements of the latest German triage consensus conference. Further validation of the concept is mandated.