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We report the design for a high-power optical parametric chirped-pulse amplifier (OPCPA) at 3200 nm central wavelength for the MIR-HE laser at ELI-ALPS, aiming to provide 20 mJ pulse energy and sub-2.5 cycles pulse length.

Active carrier envelope phase (CEP) stabilization in the few-cycle regime is essential for most attosecond experiments, e.g. studying the coherent evolution of electronic structure and dynamics in solids or complex many body phenomena crystals. Here, we present a dual-channel optical parametric chirped-pulse amplifier (OPCPA) design providing CEP stable, sub 9 fs pulses around 800 nm center wavelength as a high-harmonic driver for attosecond experiments. Additionally, a second 1.7 - 2 μm CEP stable outlet is available. Two OPCPA designs (a) high repetition rate and (b) a high pulse-energy system will be demonstrated.

High power mid-infrared (MID-IR) laser systems delivering ultrashort pulses at high repetition rates are of considerable interest for vibrational spectroscopy, label-free microscopy, ultrafast dynamics and HHG studies. To meet these requirements, we developed an optical parametric chirped-pulse amplifier (OPCPA) with a difference frequency generation (DFG) stage to provide an efficient platform to down-convert a 200 W Yb-YAG pump laser into the MID-IR range. The MID-IR pulses are tunable from 4.2-11 μm, with a maximum pulse energy around 9 μm with 2.2 μJ at 200 kHz supporting a Fourier limit of 50 fs. In addition, thermal parameters of various nonlinear crystals are reviewed for high power MID-IR OPCPAs.

An optical parametric chirped-pulse amplifier (OPCPA) system is presented, capable of providing ultrashort laser pulses at all relevant central wavelengths, from 920 to 1700 nm, for 2- and 3-photon imaging applications with repetition rates up to 10 MHz for ultrafast image acquisition.

High power and high repetition rate femtosecond lasers at 1.45–2.40 μm wavelength are critical for many applications in the physical, chemical, and biological sciences, such as microchip electron accelerators and soft-X-ray coherent diffractive imaging. Previously, such systems have been realized by optical parametric amplification from Ti:Sapphire lasers at 800 nm with limited power levels. A novel optical parametric chirped-pulse amplifier (OPCPA), pumped by high-power Yb-doped solid state laser, and combined with bulk crystal white-lightgeneration seeding (WLG) is demonstrated here. The laser system features tunable and broadband operation in the 1.45–2.40 μm spectral range, requiring no complex cooling with a compact footprint. Such systems have recently become commercially available from Class 5 Photonics and allow for scalability up to millijoule pulse energies at 100 W average power.

A compact high power OPCPA system with ultrashort pulses at wavelengths ranging from 850 to 1700 nm with single or multiple output channels is presented for 2- and 3-photon in- vivo brain imaging.

A high repetition rate, optical-parametric chirped-pulse amplifier system and high-harmonic-generation source is presented for photoelectron spectroscopy experiments spanning an ultra-wide frequency range from Terahertz to the extreme-ultraviolet range between 21.7 and 50 eV.

A high repetition rate, optical parametric chirped-pulse amplifier (OPCPA) with dual output at 800 nm and 2 µm is presented. White light seeded, CEP stabilized pulses with 9.1 fs are achieved on less than a square-meter footprint.

Embryo surface disinfection is utilized in aquaculture to decrease the risk of pathogen introduction into established colonies. Zebrafish embryos are commonly disinfected with unbuffered sodium hypochlorite at 25–50 ppm for 10 min with or without concurrent treatment with chemicals, including pronase (Pron), sodium thiosulfate, and/or methylene blue; however, the impact of these chemicals on embryo survival and development has not been evaluated. In this study, AB and casper embryos were exposed to disinfection protocols that used Pron, sodium thiosulfate, and/or methylene blue (given alone, in various combinations, or all three combined) with 50 and 100 ppm sodium hypochlorite performed 6 and 24 h postfertilization (HPF). All groups were evaluated for survival, hatching, and malformations at 5 days postfertilization. Maximal survival (69%–97%) and hatching rates (66%–94%) were generally observed with sodium hypochlorite disinfection followed by exposure to both Pron and sodium thiosulfate and maintenance in standard embryo medium without methylene blue. Methylene blue had variable effects on survival and hatching. Higher survival and hatching rates were seen in AB embryos disinfected at 6 HPF and casper embryos disinfected at 24 HPF. Susceptibility to sodium hypochlorite toxicity differed by strain, emphasizing the need to test disinfection protocols on small embryo cohorts.

Die Nutzung des Verfahrens Innenhochdruckumformen setzt ein hohes Erfahrungswissen im Werkzeugbau und in der Technologieentwicklung voraus, weshalb dies meist nur für Großunternehmen kommerziell tragfähig ist. Um hier auch KMU den Zugang zu erleichtern, wurde ein Konzept erarbeitet, mit dem die Technologieentwicklung für Applikationen auch online durchgeführt werden kann. Ziel ist es, mit generischen Datenbausteinen und wiederkehrenden Geschäftsszenarien eine virtuelle, vernetzte Technologieentwicklung mit dazu geeigneter Wissensdatenbank zu schaffen. The use of internal high pressure forming requires a high level of experience in tool making and technology development, making it commercially viable for large companies only. To facilitate access for SME, a concept has been developed for online technology development of applications. The aim is to enable virtual, linked technology development with a suitable knowledge database using generic data blocks and recurring business scenarios.

A dual-channel, high-power laser system with gap-less tuning from 250 - 1300 nm at 30 - 50 femtoseconds pulse duration is presented as the ideal tool for time-resolved photo-emission microscopy and spectroscopy experiments.

Ultrafast dynamics experiments in physics, chemistry and biology, in condensed matter or gas phase require different types of lasers. We present various OPCPAs as a powerful toolbox to deliver femtosecond pulses from the XUV to THz spectral region. A synchronized pump-probe laser has been realized, generating visible and near-IR pump pulses (350-1300 nm) and UV pulses (250 - 350 nm) operating at 4 MHz. Furthermore, a 1.55 μm wavelength OPCPA has been demonstrated for efficient THz-generation. For XUV generation in the water window, an OPCPA is presented, delivering millijoule-level, femtosecond pulses from 1.7 - 2.2 μm with up to 100 W average power.

A review of current high power (100 W-level), femtosecond, optical parametric chirped-pulse amplifiers (OPCPA) at near IR (NIR) and short-wave IR (SWIR) wavelengths pumped by Yb-based solid-state lasers is presented. OPCPA technology together with white-light-generation (WLG) makes it possible to provide CEP-stable femtosecond broadband or tunable pulses (from 700nm to 2.1 μm), which are potentially scalable to much high power levels. An important feature of these new OPCPAs is their reliability and compact design, requiring no complex cooling systems.

High power and high repetition rate femtosecond lasers are crucial tools furthering the scientific development across many fields. So far, these systems have been realized by Ti:Sapphire lasers at 800 nm, being limited in power scaling. A novel optical parametric chirped-pulse amplifier (OPCPA), pumped by high-power Yb-doped solid state lasers, and combined with bulk crystal white-light-generation seeding (WLG) allows to circumvent the limitation in average power. The presented laser system features carrier-envelope phase (CEP) stable sub 20 fs pulses centered at 800nm with millijoule pulse energies and average power of 20W while remaining on a compact footprint. Such systems have recently become commercially available from Class 5 Photonics and allow for scalability beyond millijoule pulse energies at up to 100W average power.

A high-power optical parametric chirped-pulse amplifier (OPCPA) at 1.45 – 2.40 µm wavelength, pumped by Yb-based solid-state lasers with average power scalability up to 100 W and pulse durations in the few-cycle regime is presented.

A high-power optical parametric chirped-pulse amplifier (OPCPA) at 1.45 - 2.40 pm wavelength, pumped by Yb-based solid-state lasers with average power scalability up to 100 W and pulse durations in the few-cycle regime is presented.

A high-power optical parametric chirped-pulse amplifier (OPCPA) at 2 µm wavelength, pumped by kW-class Yb:YAG InnoSlab with an average power scalability up to 100 W and pulse durations in the few-cycle regime is presented.

We present new radial velocity (RV) measurements for 11 candidate young very-low-mass stars and brown dwarfs, with spectral types from M7 to L7. Candidate young objects were identified by features indicative of low surface gravity in their optical and/or near-infrared spectra. RV measurements are derived from high resolution (R=$\lambda$/$\Delta\lambda$=20,000) $J$ band spectra taken with NIRSPEC at the Keck Observatory. We combine RVs with proper motions and trigonometric distances to calculate three-dimensional space positions and motions and to evaluate membership probabilities for nearby young moving groups (NYMGs). We propose 2MASS J00452143+1634446 (L2$\beta$, $J$=13.06) as an RV standard given the precision and stability of measurements from three different studies. We test the precision and accuracy of our RV measurements as a function of spectral type of the comparison object, finding that RV results are essentially indistinguishable even with differences of $\pm$5 spectral subtypes. We also investigate the strengths of gravity-sensitive K~{\sc i} lines at 1.24--1.25 $\mu$m and evaluate their consistency with other age indicators. We confirm or re-confirm four brown dwarf members of NYMGs -- 2MASS J00452143+1634446, WISE J00470038+6803543, 2MASS J01174748$-$3403258, and 2MASS J19355595$-$2846343 -- and their previous age estimates. We identify one new brown dwarf member of the Carina-Near moving group, 2MASS J21543454$-$1055308. The remaining objects do not appear to be members of any known NYMGs, despite their spectral signatures of youth. These results add to the growing number of very-low-mass objects exhibiting signatures of youth that lack likely membership in a known NYMG, thereby compounding the mystery regarding local, low-density star formation., Comment: 24 pages, 10 figures, 6 tables. Accepted by AJ

e21098 Background: KEAP1 mutations have been shown to decrease the efficacy of both chemotherapy (CTX) and immune-checkpoint inhibition (ICI) in lung adenocarcinoma. However, few is known about their impact on systemic treatment of squamous cell lung cancer (SqCC). The aim of this study was to assess the impact of KEAP1 mutations on systemic treatment outcome in SqCC. Methods: Tumor biopsies of SqCC patients were analyzed within the German Network Genomic Medicine (NGM) using a next-generation DNA sequencing (NGS) panel comprising 17 genes. In subsets, PD-L1 expression was tested with immunohistochemistry (IHC). MET amplification and FGFR1 amplification was tested with fluorescence in situ hybridization (FISH). Overall survival was estimated using Kaplan Meier statistics. For comparisons, we used log rank. A cohort with KEAP1 wild-type patients from the same panel served as control group. Results: Out of 1399 SqCC patients analyzed, 151 had a KEAP1 mutation (11%). The most common co-occurring mutations besides TP53 were PTEN, KRAS and NFE2L2. The median overall survival (OS) of stage IV KEAP1 mutated patients (n = 82) compared to stage IV control group patients (n = 82) was 7.3 vs. 11.4 months (hazard ratio (HR) 0.87 [95% confidence interval (CI) 0.62-1.23], p = 0.43). The addition of a second treatment line with ICI led to marked OS improvements in both KEAP1 mutant patient group (18.7 vs. 6.6 months, HR 0.11, [95% CI 0.04-0.25], p < 0.0001) and control group (20.3 vs. 5.0 months, HR 0.12 [95% CI 0.06-0.24], p < 0.0001). PD-L1 expression did not differ significantly in both groups. Conclusions: KEAP1 mutations occur commonly in SqCC patients and do not impact the efficacy of ICI in terms of OS. To identify prognostic markers for response to ICI further research is needed.

Heparine gelten im Rahmen der stationaren und zunehmend auch ambulanten Thromboseprophylaxe seit Jahrzehnten als Standardtherapie. Neben dem therapeutischen Nutzen birgt die Therapie mit Heparinen allerdings auch die Gefahr unerwunschter Nebenwirkungen wie Blutungen und Thrombozytopenien. Als schwerwiegende Nebenwirkung gilt die heparininduzierte Thrombozytopenie (HIT II). Die folgende Arbeit unterzieht die HIT II einer medizinokonomischen Betrachtung (Behandlung, Arzneimittel, Folgekosten aufgrund moglicher Komplikationen) und betrachtet im Hinblick auf eine mogliche HIT-II-Prophylaxe auch Aspekte der zunehmend im Fokus stehenden Patientensicherheit. Im Rahmen einer Literaturrecherche wurden die fur eine HIT-II-Behandlung zugelassenen Wirkstoffe Argatroban und Danaparoid evaluiert. Eine HIT II – insbesondere in Kombination mit thromboembolischen Komplikationen – bedeutet fur das Krankenhaus eine medizinokonomische Belastung. Zwar stellt dies nur eine Orientierungshilfe dar, zeigt aber auf, dass ein HIT-II-Syndrom nicht ausreichend durch das DRG-Entgeltsystem kostendeckend abgebildet wird. Eine fruhzeitige Thromboseprophylaxe mit Argatroban/Danaparoid bei HIT-II-Risikopatienten ist daher aus medizinokonomischen, aber auch aus patientensicherheitsrelevanten Gesichtspunkten in Erwagung zu ziehen. Erfahrungsgemas sollte bei diesen „medical needed“-Produkten (Antikoagulanzien) eine Arzneimittelversorgung aus Grunden der Patientensicherheit gewahrleistet sein. Das Risiko einer immunologischen Reaktion auf eine Heparintherapie ist bekannt. Im Sinne einer erhohten Patientensicherheit sollte die Thromboseprophylaxe mit einer risikoadjustierten HIT-II-Prophylaxe erfolgen.

The Hubble Space Telescope (HST) Ultraviolet Legacy Library of Young Stars as Essential Standards (ULLYSES) program is a HST Director's Discretionary program that is in the process of obtaining a large library of ultraviolet spectroscopic observations of young stars of both high and low masses. We present information on close companions to the T Tauri stars CVSO 109 and CVSO 165 in Orion that were observed with the HST as part of this program. CVSO 109 has a fainter companion at an angular separation ρ = 0.″64 near PA = 218° and Δ(F28X50LP) ≈ 0.6 mag, while the CVSO 165 companion is at ρ = 0.″30 near PA = 326° with Δ(F28X50LP) ≈ 1.7 mag. Both components of CVSO 165 appear to be active stars with strong emission features, while the CVSO 109 companion shows only modest indications of stellar activity. Extracted spectra for each of these components will be included in ULLYSES Data Release 2.

A set of twenty late-type (K5-M5) stars were observed with the Herschel Space Observatory at 100 and 160 microns with the goal of searching for far-infrared excesses indicative of the presence of circumstellar disks. Out of this sample, four stars (TYC 7443-1102-1, TYC 9340-437-1, GJ 784 and GJ 707) have infrared excesses above their stellar photospheres at either 100 or 160 micron or both. At 100 microns TYC 9340-437-1 is spatially resolved with a shape that suggests it is surrounded by a face-on disk. The 100 micron excess flux associated with GJ 707 is marginal at around 3sigma. The excess flux associated with GJ 784 is most likely due to a background galaxy as the dust radius estimated from the spectral energy fit implies that any associated dust disk should have been resolved in the Herschel images but is not. TYC 7443-1102-1 has been observed with ALMA which resolves the emission at its location into two distinct sources making the Herschel excess most likely also due to a background galaxy. It is worth noting that this star is in the 23 Myr old beta Pic association. With a disk luminosity on the order of 10^-3 L*, this system is an ideal follow-up target for high-contrast imaging and ALMA., Accepted for publication in PASP

e20577 Background: Multiple mechanisms of resistance to EGFR TKIs therapy in EGFR-mutant non-small cell lung cancer (NSCLC) have been described, most often including the acquisition of the secondary resistance mutations in exon 20 of EGFR. Preclinical models and clinical findings have also shown that co-occurring activation of the RAS/MEK pathway may result in reduced EGFR dependency, which may be overcome by co-inhibition of MEK. We thus hypothesize that the combined inhibition of EGFR and MEK may restore sensitivity to EGFR inhibition in patients with acquired resistance to EGFR inhibition and may as well prolong the acquisition of resistance in treatment-naïve patients. Methods: EATON is an international, multicenter, phase I, dose escalation investigator-initiated trial investigating the recommended phase 2 dose (RP2D), safety and preliminary efficacy of the combination of the third-generation EGFR inhibitor EGF816 with the MEK inhibitor trametinib (NCT03516214). Eligibility criteria: Advanced NSCLC harboring EGFR del19 or p.L858R, first-line or after failure of any EGFR TKI including osimertinib, independently of p.T790M status. Patients with high-level MET amplification are excluded. Dose level escalation will be based on a modified traditional cumulative 3+3 design, i.e. “up and down” (dose level 1: 100 mg nazartinib (EGF816) QD + 1 mg trametinib QD). A total number of 24 patients is planned to be enrolled in 8 trial sites in Germany and Spain. At a first stage, 18 (6´3) patients will be treated and evaluated. Exploratory endpoints aim at the identification of potential mechanisms of resistance to the trial treatment by massively parallel sequencing (MPS), FISH, phospho-protein analyses and whole exome/genome sequencing of baseline and PD biopsy tumour tissue. Additionally blood samples for MPS of cell free DNA will be collected throughout the trial treatment. Results: At the time of data-cut off for this abstract, one patient received treatment at dose-level 1. Treatment was withdrawn due to a serious, bacterial soft tissue infection of the hand outside the DLT period. Conclusions: Data on safety and tolerability of the combination of nazartinib and trametinib is premature. Updated results will be presented at the conference. Clinical trial information: NCT03516214.

Demodex musculi is a prostigmatid follicular mite that has rarely been reported in laboratory mice. Although prevalence of this species has not been assessed formally, we have found that many imported mouse strains from noncommercial sources harbor Demodex mites. To assess whether an acaricide can be used to eradicate this mite, infested immunocompromised mice were provided ivermectin-compounded (12 ppm) feed without restriction for 8 wk (n = 10), were treated topically with moxidectin and imidacloprid (MI; 3 and 13 mg/kg, respectively) weekly for 8 wk (n = 10), or remained untreated (n = 10). Mice were confirmed to be mite-infested before treatment and were tested after treatment by using fur plucks (FP), deep skin scrapes (DSS), and PCR analysis of fur swabs. In addition, the presence of mites was confirmed through skin biopsies at 2 study endpoints (1 wk [n = 5] and 12 wk [ n = 5] after treatment). Samples collected before treatment and from untreated mice were positive for D. musculi at all time points and by all test modalities. After treatment, all ivermectin-treated animals remained infested, whereas mice treated with MI were repeatedly negative by all test modalities. An additional shortened treatment trial revealed that 4 wk of MI (n = 7) was insufficient to eradicate mites. Neither treatment produced any evidence of adverse effects according to hematology, serum chemistry parameters, behavior, body weight, and histopathology. Of the 70 PCR assays performed in treated mice, 14 were positive when FP+DSS was negative. In 6 cases where PCR results were negative, 5 were positive by FP+DSS and a single sample was positive on skin biopsy. Although PCR analysis has a high detection rate for D. musculi, FP+DSS can further enhance the detection rate. In conclusion, topical MI administered for 8 consecutive weeks can safely eradicate D. musculi from an immunocompromised mouse strain.

Background: We analyzed whether co-occurring mutations influence the outcome of systemic therapy in ALK-rearranged non-small-cell lung cancer (NSCLC). Patients and methods: ALK-rearranged stage IIIB/IV NSCLC patients were analyzed with next-generation sequencing and fluorescence in situ hybridization analyses on a centralized diagnostic platform. Median progression-free survival (PFS) and overall survival (OS) were determined in the total cohort and in treatment-related sub-cohorts. Cox regression analyses were carried out to exclude confounders. Results: Among 216 patients with ALK-rearranged NSCLC, the frequency of pathogenic TP53 mutations was 23.8%, while other co-occurring mutations were rare events. In ALK/TP53 co-mutated patients, median PFS and OS were significantly lower compared with TP53 wildtype patients [PFS 3.9 months (95% CI: 2.4–5.6) versus 10.3 months (95% CI: 8.6–12.0), P < 0.001; OS 15.0 months (95% CI: 5.0–24.9) versus 50.0 months (95% CI: 22.9–77.1), P = 0.002]. This difference was confirmed in all treatment-related subgroups including chemotherapy only [PFS first-line chemotherapy 2.6 months (95% CI: 1.3–4.1) versus 6.2 months (95% CI: 1.8–10.5), P = 0.021; OS 2.0 months (95% CI: 0.0–4.6) versus 9.0 months (95% CI: 6.1–11.9), P = 0.035], crizotinib plus chemotherapy [PFS crizotinib 5.0 months (95% CI: 2.9–7.2) versus 14.0 months (95% CI: 8.0–20.1), P < 0.001; OS 17.0 months (95% CI: 6.7–27.3) versus not reached, P = 0.049] and crizotinib followed by next-generation ALK-inhibitor [PFS next-generation inhibitor 5.4 months (95% CI: 0.1–10.7) versus 9.9 months (95% CI: 6.4–13.5), P = 0.039; OS 7.0 months versus 50.0 months (95% CI: not reached), P = 0.001). Conclusions: In ALK-rearranged NSCLC co-occurring TP53 mutations predict an unfavorable outcome of systemic therapy. Our observations encourage future research to understand the underlying molecular mechanisms and to improve treatment outcome of the ALK/TP53 co-mutated subgroup.

The James Webb Space Telescope (JWST) and its suite of instruments, modes and high contrast capabilities will enable imaging and characterization of faint and dusty astrophysical sources1-3 (exoplanets, proto-planetary and debris disks, dust shells, etc.) in the vicinity of hosts (stars of all sorts, active galactic nuclei, etc.) with an unprecedented combination of sensitivity and angular resolution at wavelengths beyond 2 μm. Two of its four instruments, NIRCam4, 5 and MIRI,6 feature coronagraphs7, 8 for wavelengths from 2 to 23 μm. JWST will stretch the current parameter space (contrast at a given separation) towards the infrared with respect to the Hubble Space Telescope (HST) and in sensitivity with respect to what is currently achievable from the ground with the best adaptive optics (AO) facilities. The Coronagraphs Working Group at the Space Telescope Science Institute (STScI) along with the Instruments Teams and internal/external partners coordinates efforts to provide the community with the best possible preparation tools, documentation, pipelines, etc. Here we give an update on user support and operational aspects related to coronagraphy. We aim at demonstrating an end to end observing strategy and data management chain for a few science use cases involving coronagraphs. This includes the choice of instrument modes as well as the observing and point-spread function (PSF) subtraction strategies (e.g. visibility, reference stars selection tools, small grid dithers), the design of the proposal with the Exposure Time Calculator (ETC), and the Astronomer's Proposal Tool (APT), the generation of realistic simulated data at small working angles and the generation of high level, science-grade data products enabling calibration and state of the art data-processing.

We describe the 44 systems discovered to be within 10 parsecs of the Sun by the RECONS team, primarily via the long-term astrometry program at CTIO that began in 1999. The systems --- including 41 with red dwarf primaries, 2 white dwarfs, and 1 brown dwarf --- have been found to have trigonometric parallaxes greater than 100 milliarcseconds (mas), with errors of 0.4--2.4 mas in all but one case. We provide updated astrometric, photometric (VRIJHK magnitudes), spectral type, and multiplicity information here. Among these are 14 systems that are new entries to the 10 parsec sample based on parallaxes measured at the CTIO/SMARTS 0.9m telescope. These are the first parallaxes for nine systems, while the remaining five systems had previously measured parallaxes with errors greater than 10 mas or values placing them beyond 10 parsecs. We also present parallaxes from URAT for seven of these systems, providing additional evidence that they are closer than 10 parsecs. In addition, we provide new data for 22 systems that were previously known to lie within 10 parsecs and 9 systems reported to be closer than that horizon but for which new parallaxes place them further away. In total, we provide data for 75 systems, for which 71 have new or updated parallaxes here. The 44 systems added by RECONS comprise one of every seven systems known within 10 parsecs. We illustrate the evolution of the 10 parsec sample from the 191 systems known when the final Yale Parallax Catalog (YPC) was published in 1995 to the 316 systems known today. Even so close to the Sun, additional discoveries of red and brown dwarfs (and perhaps even white dwarfs) are likely, both as primaries and secondaries, although we estimate that at least 90% of the stellar systems closer than 10 parsecs have now been identified., submitted to AJ, 44 pages, 6 Figures, 4 Tables

Der Wettbewerb unter den Krankenhausern verscharft sich zunehmend, 42 % der Kliniken wiesen im Jahre 2013 einen Verlust aus. Der Gesetzes-Entwurf „Krankenhausstrukturgesetz – KHSG“ ist nun im Juni 2015 auf den Weg gebracht worden. Es soll u.a. die Leistungsentwicklung und DRG-Vergutung ab 2017 wesentlich beeinflussen. Medizinokonomische Herausforderungen aufgrund des zunehmenden Wettbewerbs im Krankenhausmarkt. Online-Recherche und Analyse der Literatur, Marktexpertise, Vorstellung von Handlungsoptionen fur Klinikmanager. Uberkapazitaten von Krankenhausbetten, zukunftige Wachstumsgrenzen hinsichtlich einer positiven Fallzahl- und Krankenhausbudgetentwicklung, klassische betriebswirtschaftliche Einsparungsschritte, z. B. Preisoptimierung im Einkauf, sind i. d. R. ausgeschopft. Prozessmanagement besitzt einen wachsenden Stellenwert im Hinblick auf die Optimierung der medizinokonomischen Reserven unter Einbeziehung einer weiteren Verbesserung der Patientensicherheit. Diese Aspekte sind im Hinblick auf die geplante Einfuhrung des KHSG von besonderer Relevanz. Medizinokonomische Reserven lassen sich durch eine kontinuierliche Integration eines patientenbehandlungsorientierten Prozessmanagements unter Einbeziehung eines patientenzentrierten Risikomanagement heben.

BANYAN $\Sigma$ is a new Bayesian algorithm to identify members of young stellar associations within 150 pc of the Sun. It includes 27 young associations with ages in the range ~1-800 Myr, modelled with multivariate Gaussians in 6-dimensional XYZUVW space. It is the first such multi-association classification tool to include the nearest sub-groups of the Sco-Cen OB star-forming region, the IC 2602, IC 2391, Pleiades and Platais 8 clusters, and the $\rho$ Ophiuchi, Corona Australis, and Taurus star-formation regions. A model of field stars is built from a mixture of multivariate Gaussians based on the Besan\c{c}on Galactic model. The algorithm can derive membership probabilities for objects with only sky coordinates and proper motion, but can also include parallax and radial velocity measurements, as well as spectrophotometric distance constraints from sequences in color-magnitude or spectral type-magnitude diagrams. BANYAN $\Sigma$ benefits from an analytical solution to the Bayesian marginalization integrals that makes it more accurate and significantly faster than its predecessor BANYAN II. A contamination versus hit rate analysis is presented and demonstrates that BANYAN $\Sigma$ achieves a better classification performance than other moving group classification tools, especially in terms of cross-contamination between young associations. An updated list of bona fide members in the 27 young associations, augmented by the Gaia-DR1 release, are presented. This new tool will make it possible to analyze large data sets such as the upcoming Gaia-DR2 to identify new young stars. IDL and Python versions of BANYAN $\Sigma$ are made available with this publication. (shortened), Comment: 52 pages, 12 figures, 11 tables. Accepted for publication in the Astrophysical Journal Supplement Series. Minor corrections and updated URLs

We report the detection of three small transiting planets around the young K3 dwarf K2-233 (2MASS J15215519-2013539) from observations during Campaign 15 of the K2 mission. The star is relatively nearby ($d$ = 69 pc) and bright ($V$ = 10.7 mag, $K_s$ = 8.4 mag), making the planetary system an attractive target for radial velocity follow-up and atmospheric characterization with the James Webb Space Telescope. The inner two planets are hot super-Earths ($R_b$ = 1.40 $\pm$ 0.06 R$_\oplus$, $R_c$ = 1.34 $\pm$ 0.08 R$_\oplus$), while the outer planet is a warm sub-Neptune ($R_d$ = 2.6 $\pm$ 0.1 R$_\oplus$). We estimate the stellar age to be 360$^{+490}_{-140}$ Myr based on rotation, activity, and kinematic indicators. The K2-233 system is particularly interesting given recent evidence for inflated radii in planets around similarly-aged stars, a trend potentially related to photo-evaporation, core-cooling, or both mechanisms., Accepted to AJ. 15 pages, 6 figures, 3 tables

Small cell lung cancer (SCLC) represents the most aggressive pulmonary neoplasm and is often diagnosed at late stage with limited survival, despite combined chemotherapies. We show in an autochthonous mouse model of SCLC that combined anti-VEGF/anti-PD-L1–targeted therapy synergistically improves treatment outcome compared with anti–PD-L1 and anti-VEGF monotherapy. Mice treated with anti–PD-L1 alone relapsed after 3 weeks and were associated with a tumor-associated PD-1/TIM-3 double-positive exhausted T-cell phenotype. This exhausted T-cell phenotype upon PD-L1 blockade was abrogated by the addition of anti-VEGF–targeted treatment. We confirmed a similar TIM-3–positive T-cell phenotype in peripheral blood mononuclear cells of patients with SCLC with adaptive resistance to anti–PD-1 treatment. Mechanistically, we show that VEGFA enhances coexpression of the inhibitory receptor TIM-3 on T cells, indicating an immunosuppressive function of VEGF in patients with SCLC during anti–PD-1-targeted treatment. Our data strongly suggest that a combination of anti-VEGF and anti–PD-L1 therapies can be an effective treatment strategy in patients with SCLC. Significance: Combining VEGF and PD-L1 blockade could be of therapeutic benefit to patients with small cell lung cancer. Cancer Res; 78(15); 4270–81. ©2018 AACR.

To study the in vivo functional dynamics of deep brain tissue, a high power, synchronized dual-channel laser has been developed providing laser pulse parameters: 3.8 W (4.7MHz) at 960nm (< 90fs) and 1.2W (1MHz) at 1300nm (< 70fs). Both channels are synchronized to within 5fs (rms).

Recent high-pressure and high-temperature experiments indicate that metastable olivine might persist in the cold core of a slab due to the low reaction rate of the olivine–wadsleyite phase transformation. Recent seismological observations detected a metastable olivine wedge that survives to a depth of 630 km in the Mariana slab. To consider the problem of non-equilibrium phase transformation, we developed a two-dimensional (2-D) Cartesian numerical code that incorporates the effects of kinetics into a thermal convection model. We consider the kinetics of the 410-km olivine–wadsleyite and the 660-km ringwoodite–Pv + Mw phase transformations, including the effects of water content at the 410-km phase boundary. The latent heat release of the 410-km non-equilibrium phase transformations inside the slab is also considered. The results show positive correlations between some of the controlling parameters and the length of the metastable olivine wedge: the faster the subducting velocity, and the lower the water content, the deeper is the metastable olivine wedge. With increasing depth of phase transformation, the effect of latent heat release is enhanced: heating of, at most, 100 °C occurs if olivine transforms into wadsleyite at a depth of approximately 570 km in our model setting. Temperature increase due to the latent heat released stimulates further phase transformation, resulting in further temperature increase, acting as a positive feedback effect. We also attempt to explain the seismological observations by calculating the temperature and phase structures in the Mariana slab. If we assume that the age of the Mariana slab is 150 Myr, the subduction velocity is 9.5 cm/yr, phase transformation occurs from the grain boundary of the parental phase, and the water content is 250 wt. ppm for a grain size of 1 mm, 300 wt. ppm for one of 5 mm, and 100 wt. ppm for intracrystalline transformation, then the metastable olivine wedge survives to a depth of 630 km, which is in good agreement with the seismological observations. This suggests that the deeper portion of the Mariana slab is relatively dry. Assuming that the depression of the 660-km discontinuity by ∼20–30 km within the Mariana slab, as is indicated by seismological observation, is explained by a combination of the depression caused by a negative Clapeyron slope in the cold slab and that due to the kinetics of the 660-km phase transformation, we obtain a gentle Clapeyron slope of −0.9 MPa/K for the phase transformation from ringwoodite to Pv + Mw.

Motiviert durch die zunehmende Bedeutung des Projektgeschäfts und einer dennoch oft problembehafteten Projektabwicklung, wurde ein Forschungsprojekt initiiert, das die bausteinbasierte Integration von Projektplanung, -bearbeitung und -abschluss fokussiert. Das ganzheitliche Modell unterstützt durch die sinnhafte Beschreibung von Bausteinen, Prozessen sowie technischen Funktionen eine projektbegleitende Erstellung von Projektabschlussdokumentation und Projektabschlussbericht. Project-oriented work has become increasingly important. However, many projects lack comprehensive documentation of project-related operational tasks. This paper introduces an integrative model of building blocks for project planning, execution and completion which supports project documentation and the preparation of final project reports. The model defines the essential building blocks, processes and technical functions required for a software prototype.

Industrie 4.0 bietet für die produzierende Industrie in Deutschland erhebliche Potentiale zur Steigerung der Wettbewerbsfähigkeit. Die Anwendung und volle Ausnutzung der Möglichkeiten entsprechender Technologien sind jedoch an bestimmte Voraussetzungen gebunden. Der Fachbeitrag reflektiert vor diesem Hintergrund die Umsetzungspotentiale von Industrie 4.0 in der Textilindustrie. Industry 4.0, also called Integrated Industry, provides considerable potential for the manufacturing industry in Germany to increase its competitiveness. However, the application and the full exploitation of the potential of those technologies depend on certain conditions. Against this background, the article reflects on the implementation potential of Industrie 4.0 in the textile industry.

A colony of B6.Cg-Rag1tm1Mom Tyrp1B-w Tg(Tcra,Tcrb)9Rest (TRP1/TCR) mice presented with ocular lesions and ulcerative dermatitis. Histopathology, skin scrapes, and fur plucks confirmed the presence of Demodex spp. in all clinically affected and subclinical TRP1/TCR mice examined (n = 48). Pasteurella pneumotropica and Corynebacterium bovis, both opportunistic pathogens, were cultured from the ocular lesions and skin, respectively, and bacteria were observed microscopically in abscesses at various anatomic locations (including retroorbital sites, tympanic bullae, lymph nodes, and reproductive organs) as well as the affected epidermis. The mites were identified as Demodex musculi using the skin fragment digestion technique. Topographic analysis of the skin revealed mites in almost all areas of densely haired skin, indicating a generalized demodecosis. The percentage of infested follicles in 8- to 10-wk-old mice ranged from 0% to 21%, and the number of mites per millimeter of skin ranged from 0 to 3.7. The head, interscapular region, and middorsum had the highest proportions of infested follicles, ranging from 2.3% to 21.1% (median, 4.9%), 2.0% to 16.6% (8.1%), and 0% to 17% (7.6%), respectively. The pinnae and tail skin had few or no mites, with the proportion of follicles infested ranging from 0% to 3.3% (0%) and 0% to 1.4% (0%), respectively. The number of mites per millimeter was strongly correlated with the percentage of infested follicles. After administration of amoxicillin-impregnated feed (0.12%), suppurative infections were eliminated, and the incidence of ulcerative dermatitis was dramatically reduced. We hypothesize that the Rag1-null component of the genotype makes TRP1/TCR mice susceptible to various opportunistic infestations and infections, including Demodex mites, P. pneumotropica, and C. bovis. Therefore, Rag1-null mice may serve as a useful model to study human and canine demodecosis. D. musculi should be ruled out as a contributing factor in immunocompromised mouse strains with dermatologic manifestations.

Zielsetzung: Arzneimittelumstellungen erfolgen in Krankenhausern aufgrund einer Reihe von Uberlegungen wie z. B. verbesserte Wirksamkeit oder Vertraglichkeit, Generierung von Einkaufsvorteilen, pharmazeutische Innovation oder Lieferengpasse. Ziel dieser Arbeit sind die Erstellung eines Prozessmodells fur die Durchfuhrung von Produktumstellungen und die Ermittlung eines krankenhausindividuellen Schwellenwerts, ab dem eine Arzneimittelproduktumstellung bei gegebener Wirksamkeit und Sicherheit des neuen Produkts deckungsbeitragsbezogen sinnvoll ist. Methodik: Der Aufwand einzelner Arzneimittelumstellungen im Munchner Klinikum rechts der Isar (MRI) wurde in einem Prozessmodell abgebildet. Die Prozessmodule wurden zeitlich erfasst und anschliesend im Rahmen einer Prozesskostenrechnung bewertet. Ergebnisse: Arzneimittelumstellungen teilen sich in drei Arten von Produktumstellungen auf: generische Umstellungen, wirkstoffgleiche Umstellungen mit Namensanderung und komplexe Umstellungen, bei denen sich Wirkstoff oder Arzneiform andert. Insbesondere Letztere sind mit einem deutlich hoheren Informationsbedarf verbunden. Dies spiegelt sich ebenfalls in der Prozesskostenanalyse wider. Relevante Kosten entstehen dabei im Rahmen des Vergabeverfahrens sowie an den anfordernden Verbrauchsstellen. Die Umstellungskosten inklusive Gemeinkosten im MRI liegen abhangig von der Anforderungshaufigkeit und der Komplexitat des umzustellenden Produkts zwischen 2.300.– € und 6.420.– €. Schlussfolgerung: Die HTA-Betrachtung (Health Technology Assessment) von Arzneimittelumstellungen im Krankenhaus zeigt, dass als Hauptkostenfaktor bei einer Arzneimittelumstellung die zusatzlichen Personalaufwendungen an den Verbrauchsstellen zu beachten sind. Sinnvoll gesetzte Schwellenwerte dienen dabei als Entscheidungshilfe bei der Abwagung zwischen Wirtschaftlichkeit und Risiko fur die Arzneimitteltherapiesicherheit sowie Patientensicherheit bei einer geplanten Arzneimittelumstellung.