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Vaccines against SARS-CoV-2 that induce mucosal immunity capable of preventing infection and disease remain urgently needed. In this study, we demonstrate the efficacy of Bordetella colonization factor A (BcfA), a novel bacteria-derived protein adjuvant, in SARS-CoV-2 spike-based prime-pull immunizations. We show that i.m. priming of mice with an aluminum hydroxide– and BcfA-adjuvanted spike subunit vaccine, followed by a BcfA-adjuvanted mucosal booster, generated Th17-polarized CD4+ tissue-resident memory T cells and neutralizing Abs. Immunization with this heterologous vaccine prevented weight loss following challenge with mouse-adapted SARS-CoV-2 (MA10) and reduced viral replication in the respiratory tract. Histopathology showed a strong leukocyte and polymorphonuclear cell infiltrate without epithelial damage in mice immunized with BcfA-containing vaccines. Importantly, neutralizing Abs and tissue-resident memory T cells were maintained until 3 mo postbooster. Viral load in the nose of mice challenged with the MA10 virus at this time point was significantly reduced compared with naive challenged mice and mice immunized with an aluminum hydroxide–adjuvanted vaccine. We show that vaccines adjuvanted with alum and BcfA, delivered through a heterologous prime-pull regimen, provide sustained protection against SARS-CoV-2 infection.

In view of the required energy savings in the building sector, there is an urgent need for innovative and sustainable solutions to increase the performance of building envelopes. Adaptive façades can make an important contribution, whereby passive low-tech strategies and active high-tech solutions are apparently incompatible. In current digitalization, new technologies and methods for the implementation of adaptive façades emerge in the framework of Cyber-Physical Systems. The investigation follows the research question: How can active and passive approaches of adaptive façades be mediated and what potential do Cyber-Physical Systems have for the implementation of hybrid solution approaches in the future? The article presents a comparative case study of the two research projects ADAPTEX and PRÄKLIMA as examples of passive and active adaptation strategies in the façade industry. In this context, the potential for further research of Cyber-Physical Systems in the application domain of adaptive façades as a catalyst for high-performance and multifunctional solutions, and as a mediator between both strategies, is highlighted. The main findings are the potential application of cyber-physical system technologies to the design and monitoring of passive adaptive façade solutions, as well as the possible integration of passively conceptualized components into active overall systems.

Background Complete mesocolic excision (CME) for right colonic cancer is a more complex operation than standard right hemicolectomy but evidence to support its routine use is still limited. This prospective multicentre study evaluated the effect of CME on long-term survival in colorectal cancer centres in Germany (RESECTAT trial). The primary hypothesis was that 5-year disease-free survival would be higher after CME than non-CME surgery. A secondary hypothesis was that there would be improved survival of patients with a mesenteric area greater than 15 000 mm2. Methods Centres were asked to continue their current surgical practices. The surgery was classified as CME if the superior mesenteric vein was dissected; otherwise it was assumed that no CME had been performed. All specimens were shipped to one institution for pathological analysis and documentation. Clinical data were recorded in an established registry for quality assurance. The primary endpoint was 5-year overall survival for stages I–III. Multivariable adjustment for group allocation was planned. Using a primary hypothesis of an increase in disease-free survival from 60 to 70 per cent, a sample size of 662 patients was calculated with a 50 per cent anticipated drop-out rate. Results A total of 1004 patients from 53 centres were recruited for the final analysis (496 CME, 508 no CME). Most operations (88.4 per cent) were done by an open approach. Anastomotic leak occurred in 3.4 per cent in the CME and 1.8 per cent in the non-CME group. There were slightly more lymph nodes found in CME than non-CME specimens (mean 55.6 and 50.4 respectively). Positive central mesenteric nodes were detected more in non-CME than CME specimens (5.9 versus 4.0 per cent). One-fifth of patients had died at the time of study with recorded recurrences (63, 6.3 per cent), too few to calculate disease-free survival (the original primary outcome), so overall survival (not disease-specific) results are presented. Short-term and overall survival were similar in the CME and non-CME groups. Adjusted Cox regression indicated a possible benefit for overall survival with CME in stage III disease (HR 0.52, 95 per cent c.i. 0.31 to 0.85; P = 0.010) but less so for disease-free survival (HR 0.66; P = 0.068). The secondary outcome (15 000 mm2 mesenteric size) did not influence survival at any stage (removal of more mesentery did not alter survival). Conclusion No general benefit of CME could be established. The observation of better overall survival in stage III on unplanned exploratory analysis is of uncertain significance.

The myotendinous junction (MTJ) is a specialized domain of the multinucleated myofibre that is faced with the challenge of maintaining robust cell–matrix contact with the tendon under high mechanical stress and strain. Here, we profiled 24,124 nuclei in semitendinosus muscle–tendon samples from three healthy males by using single-nucleus RNA sequencing (snRNA-seq), alongside spatial transcriptomics, to gain insight into the genes characterizing this specialization in humans. We identified a cluster of MTJ myonuclei represented by 47 enriched transcripts, of which the presence of ABI3BP, ABLIM1, ADAMTSL1, BICD1, CPM, FHOD3, FRAS1 and FREM2 was confirmed at the MTJ at the protein level in immunofluorescence assays. Four distinct subclusters of MTJ myonuclei were apparent, comprising two COL22A1-expressing subclusters and two subclusters lacking COL22A1 expression but with differing fibre type profiles characterized by expression of either MYH7 or MYH1 and/or MYH2. Our findings reveal distinct myonuclei profiles of the human MTJ, which represents a weak link in the musculoskeletal system that is selectively affected in pathological conditions ranging from muscle strains to muscular dystrophies.

A hallmark of pancreatic ductal adenocarcinoma (PDAC) is an exuberant stroma comprised of diverse cell types that enable or suppress tumor progression. Here, we explored the role of oncogenic KRAS in protumorigenic signaling interactions between cancer cells and host cells. We show that KRAS mutation (KRAS*) drives cell-autonomous expression of type I cytokine receptor complexes (IL2rγ–IL4rα and IL2rγ–IL13rα1) in cancer cells that in turn are capable of receiving cytokine growth signals (IL4 or IL13) provided by invading Th2 cells in the microenvironment. Early neoplastic lesions show close proximity of cancer cells harboring KRAS* and Th2 cells producing IL4 and IL13. Activated IL2rγ–IL4rα and IL2rγ–IL13rα1 receptors signal primarily via JAK1–STAT6. Integrated transcriptomic, chromatin occupancy, and metabolomic studies identified MYC as a direct target of activated STAT6 and that MYC drives glycolysis. Thus, paracrine signaling in the tumor microenvironment plays a key role in the KRAS*-driven metabolic reprogramming of PDAC.Significance:Type II cytokines, secreted by Th2 cells in the tumor microenvironment, can stimulate cancer cell–intrinsic MYC transcriptional upregulation to drive glycolysis. This KRAS*-driven heterotypic signaling circuit in the early and advanced tumor microenvironment enables cooperative protumorigenic interactions, providing candidate therapeutic targets in the KRAS* pathway for this intractable disease.

Supplementary Figures 1-6

Background Leakage of rectal anastomoses is one of the most important and feared complications in colorectal surgery. Apart from patient-specific risk factors, technical aspects may influence the occurrence of anastomotic complications. This study investigated whether using single-stapling techniques (SST) instead of the double-stapling technique (DST) for minimal-invasive rectal anastomosis is associated with a lower rate of anastomotic complications. Methods A retrospective review of 272 patients who received a minimally invasive stapled rectal anastomosis (3–16 cm from the anal verge) at our institution from 2015 to 2020 was performed. In 131 patients, rectal anastomosis was created by SST (SST group), while 141 patients received a rectal anastomosis with crossing stapler lines (DST group). The impact of the anastomotic technique on patient outcomes was determined by uni- and multivariate analyses. Results Overall anastomotic leakage rate was 6%. Patients with SST anastomoses had a lower leakage rate than patients with DST anastomoses (3% vs. 9% in the DST group, p = 0.045). The rate of anastomotic stenosis was lower in the SST group than in the DST group (1% vs. 6%, p = 0.037). Overall morbidity and mortality did not differ between the two groups. Multivariate analysis showed that single-stapling techniques significantly reduce the risk of anastomotic leakage (OR 3.5 [1.0–11.5], p = 0.043). Conclusion The use of SST for rectal anastomosis may help to reduce anastomotic complications. This finding should be confirmed by a randomized controlled trial.

In the world of computer security, attackers are constantly looking for new exploits to gain data from or control over a computer system. One category of exploit that can prove quite effective at accessing privileged data is side channel exploits. These exploits attempt to take advantage of vulnerabilities that are inherent in the design of a system rather than vulnerabilities in the code that has been written for and is running on said system. In other words, they exploit side effects of computation. Examples of this include measuring the power consumption of a system’s processor over time and analysing that power usage to leak system secrets or reading secrets from a system by analysing the electromagnetic radiation the system leaks as it processes data. Another type of side channel attack is a cache-based side channel attack, which exploits the timings of cache and memory accesses to determine data from the target system. We discuss some of the more common types of side channel attacks used to interpret data values from the microarchitectural changes created by transient executions. In particular, we will focus on attacks that are capable of recovering data that is processed through transient execution in some way and then wrongly accessed using a side channel, such as the Spectre and Meltdown classes of attack. We also discuss other attacks of a similar type and survey some popular mitigations for these attacks. We provide a survey of all available Spectre proof-of-concept repositories on GitHub, evaluating whether they work on different platforms. Finally, we review our experiences with these types of attacks on modern systems and comment on the attacks’ practicality, reliability, and portability. We conclude that these types of attacks are interesting, but there are some practicality and reliability concerns that make other attacks easier much of the time.

Colon cancer (CC) is a disease of elderly patients (pts.) with a median age of 73 years (yrs.). Lack of data about the effects of adjuvant chemotherapy (ACT) is caused by underrepresentation of this clinically relevant cohort in interventional trials. We analyzed real-world data from the German CPP registry with regard to a possible benefit of ACT in elderly (70+ yrs.) versus younger pts. (50 to70 yrs.) taking cause-specific deaths into account.We analyzed the effect of age and ACT on overall survival (OS) and cause-specific death of stage III pts. using Cox regression.In total, 1558 pts. were analyzed and follow-up was 24.6 months. 62.6% of the elderly received ACT whereas 91.1% of younger pts. (p 0.001). Oxaliplatin combinations were significantly less often given to older than younger pts. (38.8% vs. 88.9%; p 0.001). Mean Charlson comorbidity score was significantly lower in pts. that received ACT (0.61) than in those without ACT (1.16; p 0.001). ACT was an independent positive prognostic factor for cancer-related death in elderly pts. even in pts. 75+ yrs. No significant difference in the effect of ACT could be observed between age groups (interaction: cancer-specific death HR = 1.7948, p = 0.1079; death of other cause HR = 0.7384, p = 0.6705).ACT was an independent positive prognostic factor for OS. There may be a cohort of elderly with less co-morbidities who benefit from ACT.

Photovoltaic installations will likely become one of the major power sources in the 21st century and we need photovoltaic modules to operate reliably. In this review, we explore what is known today about the status of installed crystalline silicon photovoltaic modules in the world, how different sources classify module defects, and what we might deduce for future installations. Looking at more than 200 results from 132 installations and 79 reports, we find that PV modules in general are robust in outdoor operation, with about one in 250 modules failing completely each year. About one in ten modules will develop a defect resulting in greater than expected power loss throughout their lifetime, and practically every module will develop visually perceivable alterations. We observe no trends of changes over time in these findings, hence there is no indication that future performance will deviate dramatically. We note though that more information is needed. Available studies represent a module fleet with greater age than current installations, and are over-representing multicrystalline – compared to monocrystalline silicon, and AL-BSF – compared to PERC cell architectures. Studies from Asia and Africa and from tropical climates are underrepresented. A major challenge in the analysis was the variety of metrics used. To facilitate easier comparison, we propose reporting guidelines.

Supplementary Data from Tumor-associated CD75s- and iso-CD75s-gangliosides are potential targets for adjuvant therapy in pancreatic cancer

Pancreatic adenocarcinoma confers one of the highest mortality rates in malignant human tumors with very poor prognosis. Because as yet no treatments are available that produce a substantial survival benefit for this fatal neoplasia, new therapeutic concepts are urgently required to support cancer standard treatment. In search of tumor-associated gangliosides with therapeutic background, we probed a random collection of cancerous and adjacent normal postoperative tissue samples from 38 patients for the expression of CD75s- and iso-CD75s-gangliosides. We exhaustively analyzed the expression of CD75s-1-ganglioside (IV6Neu5Ac-nLc4Cer) and structurally closely related iso-CD75s-1-ganglioside (IV3Neu5Ac-nLc4Cer) by means of immunohistology of cryosections and semiquantitative TLC of tissue lipid extracts combined with mass spectrometry. CD75s-1- and iso-CD75s-1-ganglioside showed an elevated expression in 42% and 66% of the tumors, respectively, indicating a significant association with neoplastic transformation (P = 0.001). Thus, increased expression of CD75s-1- and iso-CD75s-1-gangliosides renders these cell surface molecules promising candidates for oncologic applications. Further statistical analysis revealed a significant enhancement of CD75s-1-ganglioside in the group of less differentiated tumors (grade >2) suggesting this ganglioside as a potential marker for poor differentiation. The CD75s-specific antitumor drug rViscumin, which represents the recombinant counterpart of the ribosome-inactivating lectin viscumin, has successfully passed clinical phase I trials and provides an opportunity for treating pancreatic cancer. Consequently, if an enhanced expression is existent in malignant tissues, we propose the targeting of CD75s-gangliosides with rViscumin as a novel potential strategy in adjuvant treatment of pancreatic malignancies. [Mol Cancer Ther 2008;7(8):2464–12]

Novel malaria vector control strategies targeting the odour-orientation of mosquitoes during host-seeking, such as ‘attract-and-kill’ or ‘push-and-pull’, have been suggested as complementary tools to indoor residual spraying and long-lasting insecticidal nets. These would be particularly beneficial if they can target vectors in the peri-domestic space where people are unprotected by traditional interventions. A randomized double-blind placebo-control study was implemented in western Kenya to evaluate: a ‘push’ intervention (spatial repellent) using transfluthrin-treated fabric strips positioned at open eave gaps of houses; a ‘pull’ intervention placing an odour-baited mosquito trap at a 5 m distance from a house; the combined ‘push-pull’ package; and the control where houses contained all elements but without active ingredients. Treatments were rotated through 12 houses in a randomized-block design. Outdoor biting was estimated using human landing catches, and indoor mosquito densities using light-traps. None of the interventions provided any protection from outdoor biting malaria vectors. The ‘push’ reduced indoor vector densities dominated by Anopheles funestus by around two thirds. The ‘pull’ device did not add any benefit. In the light of the high Anopheles arabiensis biting densities outdoors in the study location, the search for efficient outdoor protection and effective pull components needs to continue.

The Lieb lattice and the kagome lattice, which are both well known for their Dirac cones and flat bands, can be continuously converted into each other by a shearing transformation. During this transformation, the flat band is destroyed, but the Dirac cones remain and become tilted, with types I, II, and III occurring for different parameters. In this work, we first study these tilted Dirac cones using a tight-binding model, revealing how they can be engineered into the different types. We then demonstrate conical diffraction in a photonic lattice realization of the Lieb-kagome lattice using split-step beam propagation simulations, obtaining evidence of the presence of Dirac cones tilted in different directions. Finally, we performed experiments with photonic lattices laser-written in fused silica (SiO$_2$) to validate the results of the simulations. These studies advance the understanding of the Lieb-kagome lattice and tilted Dirac cones in general and provide a basis for further research into this interesting tunable lattice system.

Purpose The aim of the present study was to identify risk factors associated with postoperative morbidity and major morbidity, with a prolonged length of hospital stay and with the need of readmission in patients undergoing appendectomy due to acute appendicitis. Methods We performed a retrospective analysis of 1638 adult patients who underwent emergency appendectomy for preoperatively suspected acute appendicitis from 2010 to 2020 at the University Hospital Erlangen. Data including patient demographics, pre-, intra-, and postoperative findings were collected and compared between different outcome groups (morbidity, major morbidity, prolonged length of postoperative hospital stay (LOS) and readmission) from those patients with verified acute appendicitis (n = 1570). Results Rate of negative appendectomies was 4%. In patients with verified acute appendicitis, morbidity, major morbidity and readmission occurred in 6%, 3% and 2%, respectively. Mean LOS was 3.9 days. Independent risk factors for morbidity were higher age, higher preoperative WBC-count and CRP, lower preoperative hemoglobin, longer time to surgery and longer duration of surgery. As independent risk factors for major morbidity could be identified higher age, higher preoperative CRP, lower preoperative hemoglobin and longer time to surgery. Eight parameters were independent risk factors for a prolonged LOS: higher age, higher preoperative WBC-count and CRP, lower preoperative hemoglobin, need for conversion, longer surgery duration, presence of intraoperative complicated appendicitis and of postoperative morbidity. Presence of malignancy and higher preoperative WBC-count were independent risk factors for readmission. Conclusion Among patients undergoing appendectomy for acute appendicitis, there are relevant risk factors predicting postoperative complications, prolonged hospital stays and readmission. Patients with the presence of the identified risk factors should receive special attention in the postoperative course and may benefit from a more individualized therapy.

Additional visualisation and energy flow

Experimentalpsychologisches Praktikum UZH FS23

The myotendinous junction (MTJ) is a specialized domain of the multinucleated myofibre, faced with the challenge of maintaining robust cell-matrix contact with the tendon under high mechanical stress and strain. Here, we profiled 24,161 nuclei in semitendinosus muscle-tendon samples from 3 healthy males by single nucleus RNA-sequencing (snRNA-seq), alongside spatial transcriptomics, to gain insight into the genes characterizing this specialization in humans. We identified a cluster of MTJ myonuclei, represented by 47 enriched transcripts, of which the presence ofABI3BP, ABLIM1, ADAMTSL1, BICD1, CPM, FHOD3, FRAS1andFREM2was confirmed at the MTJ at the protein level by immunofluorescence. Four distinct subclusters of MTJ myonuclei were apparent and segregated into two COL22A1-expressing subclusters and two lacking COL22A1 but with a clear fibre type profile expressingMYH7orMYH1/2. Our findings reveal distinct myonuclei profiles of the human MTJ, a weak link in the musculoskeletal system, which is selectively affected in pathological conditions, from muscle strains to muscular dystrophies.

Zusammenfassung Einleitung Die Delegation ärztlicher Leistungen an rheumatologische Fachassistent:innen (RFA) hat sich in der Evaluation des Forschungsprojektes „StärkeR“ als sicher und effektiv erwiesen. Im Nachgang wurden die Erfahrungen der beteiligten RFA und der Rheumatolog:innen mit der Delegation im Rahmen eines Meinungsforschungsprojekts erfragt und diskutiert. Methoden Zum Ende des Projekts wurden die teilnehmenden RFA (mittleres Alter 45 Jahre, 100 % weiblich, durchschnittlich 11 Jahre Berufserfahrung) und Rheumatolog:innen (mittleres Alter 54 Jahre, 32 % weiblich, durchschnittlich 21 Jahre Berufserfahrung), über einen Online-Fragebogen (quantitative Analyse) befragt (21 Fragen an die Ärzt:innen und 44 Fragen an die RFA). Zusätzlich fanden für die RFA Fokusgruppensitzungen statt, die von einer Moderatorin und einer Protokollführerin geleitet wurden. Die Ergebnisse der Fokusgruppensitzungen (qualitative Analysen) wurden gemäß der strukturierten Methode nach Kuckartz ausgewertet. Ergebnisse An den Online-Befragungen beteiligten sich alle im Projekt involvierten 31 RFA und 25 Rheumatolog:innen. An den beiden Fokusgruppen nahmen 9 RFA teil. In den Online-Befragungen der RFA und Ärzt:innen ergaben sich überwiegend gute bis sehr gute Bewertungen hinsichtlich RFA-Schulung, Durchführung der Delegation in den Praxen und Ambulanzen, in der Rolle der RFA und der Bewertung des Delegationskonzeptes insgesamt. In den Fokusgruppendiskussionen wurden viele mögliche Einschränkungen hinsichtlich Akzeptanz und Umsetzung des Delegationskonzeptes genannt. Schlussfolgerungen Die Delegation ärztlicher Aufgaben an RFA ist ein mehrheitlich von beiden Seiten, der Rheumatolog:innen und der RFA, positiv eingeschätztes Konzept mit hoher Akzeptanz. Im Vergleich zwischen den einzelnen Praxen und Klinikambulanzen besteht hinsichtlich der Bereitschaft und der logistischen Möglichkeiten in der Umsetzung des Delegationskonzeptes noch eine deutliche Heterogenität.

Engineered domain structures play an essential role in nonlinear optics for quasi-phase-matched parametric processes. Pyroelectric field-assisted domain inversion with focused femtosecond laser pulses is a promising approach to create arbitrary two-dimensional nonlinear photonic structures in a large volume without externally applied electrical fields. We fabricate lattices of ferroelectric domains by patterning lithium niobate crystals with femtosecond laser pulses and then heating them to elevated temperatures. After cooling to room temperature, domains form below and above the laser-induced seeds. We investigate the effect of temperature and seed spacing on the number and size of inverted domains. In a temperature range of 220 °C-300 °C all domains are inverted in a two-dimensional lattice with periods of 15 µm × 6.3 µm. Smaller lattice periods result in a smaller fraction of inverted domains. Measurements with conducting, nonconducting, and short-circuited crystal surfaces reveal the influence of surface charges during the domain formation process. From the obtained domain widths and spacings, we calculate the effective nonlinear coefficient of quasi-phase-matched second-harmonic generation in two-dimensional nonlinear photonic structures.

Novel diffractive surface structures are designed, evaluated, and optimized to achieve a significant increase in current density in organic solar cells. The surface relief phase gratings are patterned based on concentric rings, a Fermat's spiral, and an Archimedean spiral, respectively, and thus diffract incident light independent of its azimuthal angle, as they all exhibit circularly symmetric diffraction patterns. The grating pillars are arranged on the rings or spirals according to periodic or deterministic aperiodic Thue-Morse and Rudin-Shapiro sequences, tailoring the desired diffraction patterns. After evaluating the surface patterns against each other and further parameter optimization, a final current density enhancement of 5 % is achieved for one of the most promising patterns, the Thue-Morse sequence on an Archimedean spiral.

Accelerating beams, of which the Airy beam is an important representative, are characterized by intensity maxima that propagate along curved trajectories. In this work we present a simple approach to directly generate accelerating beams with controllable trajectories by means of binary phase structures that consist of only a π phase step modulation in comparison to previous studies where two-dimensional cubic phase modulations for example are required, and which have practical limitations due to their challenging fabrication with phase plates or diffractive optical elements (DOEs), or the spatially extended system needed for their generation at the Fourier plane. In our approach, two intensity maxima are formed that propagate along root parabolic trajectories in contrast to Airy and higher order caustic beams that propagate along a parabolic curve, hence we call these beams Dual Projectile Beams (DPBs). By tailoring a step or slit phase patterns with additional Fresnel lenses, we either generate hollow-core or abruptly focusing beams and control their curvatures. Moreover, using DPBs as a simpler complement to complex structured light fields, we demonstrate their versatility at the example of their interaction with nonlinear matter, namely the formation of a spatial soliton in a photorefractive material. We show that the formed solitary state propagates almost unchanged for a distance of several Rayleigh lengths. This light matter interaction can be regarded as a light beam deceleration. The simplicity of this approach makes these beams suitable for integrated optics and high-power laser applications using DOEs or meta-surfaces.

Purpose Intestinal anastomosis is a crucial step in most intestinal resections, as anastomotic leakage is often associated with severe consequences for affected patients. There are especially two different techniques for hand-sewn intestinal anastomosis: the interrupted suture technique (IST) and the continuous suture technique (CST). This study investigated whether one of these two suture techniques is associated with a lower rate of anastomotic leakage. Methods A retrospective review of 332 patients with Crohn’s disease who received at least one hand-sewn colonic anastomosis at our institution from 2010 to 2020 was performed. Using propensity score matching 183 patients with IST were compared to 96 patients with CST in regard to the impact of the anastomotic technique on patient outcomes. Results Overall anastomotic leakage rate was 5%. Leakage rate did not differ between the suture technique groups (IST: 6% vs. CST: 3%, p = 0.393). Multivariate analysis revealed the ASA score as only independent risk factor for anastomotic leakage (OR 5.3 (95% CI = 1.2–23.2), p = 0.026). Suture technique also showed no significant influence on morbidity and the re-surgery rate in multivariate analysis. Conclusion Our data suggest that the chosen suture technique (interrupted vs. continuous) has no influence on postoperative outcome, especially on anastomotic leakage rate. This finding should be confirmed by a randomized controlled trial.

Das Verhalten hochstrittiger Trennungs- und Scheidungseltern kann verschiedene weitreichende Folgen für Kinder haben. Kinder können durch die lange andauernden elterlichen Konflikte stark belastet und in ihrem Wohl gefährdet werden. Stellen die massiven elterlichen Konflikte eine Kindeswohlgefährdung dar oder müssen kindesrechtliche Belange geregelt werden, führt die Kindes- und Erwachsenenschutzbehörde (KESB) ein Abklärungsverfahren durch. Die Arbeit mit hochstrittigen Eltern kann für die involvierten Fachpersonen eine grosse Herausforderung darstellen. Es soll der Frage nachgegangen werden, wie kindesschutzrechtliche Abklärungsverfahren mit hochstrittigen Eltern deeskalierend und zum Wohl des Kindes gestaltet werden können. Dies geschieht durch das Aufzeigen verschiedener Merkmale der Hochstrittigkeit und deren Auswirkungen auf das Kind und die Eltern, dem Vorstellen der rechtlichen Ausgangslage bei der KESB sowie der Auseinandersetzung mit verschiedenen Methoden in der Zusammenarbeit mit hochstrittigen Eltern. Die Fragestellung wurde anhand einer Literaturarbeit mit dem Titel «Kinder und ihre hochstrittigen Eltern in kindesschutzrechtlichen Abklärungsverfahren» bearbeitet. Durch Fachkenntnisse über Hochstrittigkeit und dem Bestimmen des elterlichen Konfliktniveaus werden methodisches Vorgehen und passende Interventionen innerhalb des gesetzlichen Rahmens abgeleitet, welche das Kind wieder ins Zentrum rücken und deeskalierend wirken können. Eine allgemein gültige Vorgehensweise kann in dieser Arbeit nicht aufgezeigt werden, da jeder Fall individuell zu betrachten ist und massgeblich von den Eltern und ihrem Verhalten abhängig ist., + Code Diss LU: hslusa basa be + Fussnote: Bachelor-Arbeit, Hochschule Luzern – Soziale Arbeit, Studienrichtung Sozialarbeit, 2022 + NL-Code: NLLUHSA202209

Zusammenfassung Hintergrund Bereits während der ersten Welle der COVID-19-Pandemie wurden die deutschen Krankenhäuser dazu aufgefordert, ihre elektiven Operationskapazitäten einzuschränken, um eine Überlastung des Gesundheitswesens abzuwenden. Im März 2020 wurden mit dem COVID-19-Krankenhausentlastungsgesetz finanzielle Hilfen zum Ausgleich dieser Einschränkungen vereinbart. Die Auswirkungen dieser Maßnahmen wurden in dieser Studie regional untersucht. Material und Methoden Es wurden die Leistungsdaten und Erlöskennzahlen der Klinik für Allgemein- und Viszeralchirurgie des Universitätsklinikums Erlangen (UKER) und der Chirurgischen Abteilung des Kreiskrankenhauses St. Anna Höchstadt/Aisch (KKH) im Zeitraum 01.04. bis 30.06.2019 mit denen des Jahres 2020 verglichen. Ergebnisse Es zeigte sich eine deutliche Reduktion der Bettenauslastung und der Fallzahlen stationär behandelter Patienten. Letztere sanken um 20,06 % im UKER bzw. 60,76 % im KKH. Nichtonkologische elektive Operationen nahmen um 33,04 % (UKER) bzw. 60,87 % (KKH) ab. Die Anzahl der Notfalleingriffe blieb am UKER unverändert und verringerte sich am KKH um 51,58 %.Die Erlöse aus DRG („diagnosis-related groups“) sanken um 22,12 % (UKER) und 54 % (KKH). Nach Berücksichtigung der Ausgleichszahlungen und Einsparungen aus variablen Sachkosten verzeichnete das UKER einen Verlust von −3,87 %, das KKH erreichte hingegen einen positiven Erlöseffekt von 6,5 %. Diskussion Die nichtselektive Einschränkung des elektiven Operationsbetriebs beeinflusste die Patientenversorgung und die Erlöskennzahlen an beiden Standorten signifikant. In Bezug auf die Schaffung von Intensivkapazitäten erscheint diese ungezielte Maßnahme jedoch nicht effizient. Zudem führte die einheitliche Freihaltepauschale zu einer unausgeglichenen Verteilung der finanziellen Hilfen zwischen den untersuchten Kliniken.

Controlling random light is a key enabling technology that pioneered statistical imaging methods like speckle microscopy. Such low-intensity illumination is especially useful for bio-medical applications where photobleaching is crucial. Since the Rayleigh intensity statistics of speckles do not always meet the requirements of applications, considerable effort has been dedicated to tailoring their intensity statistics. A special random light distribution that naturally comes with radically different intensity structures to speckles are caustic networks. Their intensity statistics support low intensities while allowing sample illumination with rare rouge-wave-like intensity spikes. However, the control over such light structures is often very limited, resulting in patterns with inadequate ratios of bright and dark areas. Here, we show how to generate light fields with desired intensity statistics based on caustic networks. We develop an algorithm to calculate initial phase fronts for light fields so that they smoothly evolve into caustic networks with the desired intensity statistics during propagation. In an experimental demonstration, we exemplarily realize various networks with a constant, linearly decreasing and mono-exponential probability density function.

The RREB1::MRTFB (former RREB1::MKL2) fusion characterizes ectomesenchymal chondromyxoid tumors (EMCMT) of the tongue. Only five molecularly confirmed extra-glossal EMCMT cases have been reported recently; all occurring at head and neck or mediastinal sites. We herein describe five new cases including the first two extracranial/extrathoracic cases. The tumors occurred in three male and two female patients with an age ranging from 18 to 61 years (median, 28). Three tumors were located in the head and neck (jaw, parapharyngeal space, and nasopharyngeal wall) and two in the soft tissue (inguinal and presacral). The tumor size ranged from 3.3 to 20 cm (median, 7). Treatment was surgical without adjuvant treatment in all cases. Two cases were disease-free at 5 and 17 months; other cases were lost to follow-up. Histologically, the soft tissue cases shared a predominant fibromyxoid appearance, but with variable cytoarchitectural pattern (cellular perineurioma-like whorls and storiform pattern in one case and large polygonal granular cells embedded within a chondromyxoid stroma in the other). Two tumors (inguinal and parapharyngeal) showed spindled to ovoid and round cells with a moderately to highly cellular nondescript pattern. One sinonasal tumor closely mimicked nasal chondromesenchymal hamartoma (NCMH). Mitotic activity was low (0-5 mitoses/10 hpfs). Immunohistochemical findings were heterogeneous with variable expression of S100 (2/5), EMA (2/3), CD34 (1/4), desmin (1/4), and GFAP (1/3). Targeted RNA sequencing revealed the same RREB1::MRTFB fusion in all cases, with exon 8 of RREB1 being fused to exon 11 of MRTFB. This study expands the topographic spectrum of RREB1::MRTFB fusion-positive mesenchymal neoplasms, highlighting a significant morphological and phenotypic diversity. Overall, RREB1::MRTFB-rearranged neoplasms seem to fall into two subcategories: tumors with lobulated, chondroid, or myxochondroid epithelioid morphology (Cases 2 and 3) and those with more undifferentiated hypercellular spindle cell phenotype (Cases 1, 4, and 5). Involvement of extracranial/extrathoracic sites and the NCMH-like pattern are novel. The biology of these likely indolent or benign tumors remains to be verified in the future.

Severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) is a worldwide health concern, and new treatment strategies are needed. Targeting inflammatory innate immunity pathways holds therapeutic promise, but effective molecular targets remain elusive. Here, we show that human caspase-4 (CASP4) and its mouse homolog, caspase-11 (CASP11), are up-regulated in SARS–CoV-2 infections and that CASP4 expression correlates with severity of SARS–CoV-2 infection in humans. SARS–CoV-2–infected Casp11−/− mice were protected from severe weight loss and lung pathology, including blood vessel damage, compared to wild-type (WT) mice and mice lacking the caspase downstream effector gasdermin-D (Gsdmd−/−). Notably, viral titers were similar regardless of CASP11 knockout. Global transcriptomics of SARS–CoV-2–infected WT, Casp11−/−, and Gsdmd−/− lungs identified restrained expression of inflammatory molecules and altered neutrophil gene signatures in Casp11−/− mice. We confirmed that protein levels of inflammatory mediators interleukin (IL)-1β, IL-6, and CXCL1, as well as neutrophil functions, were reduced in Casp11−/− lungs. Additionally, Casp11−/− lungs accumulated less von Willebrand factor, a marker for endothelial damage, but expressed more Kruppel-Like Factor 2, a transcription factor that maintains vascular integrity. Overall, our results demonstrate that CASP4/11 promotes detrimental SARS–CoV-2–induced inflammation and coagulopathy, largely independently of GSDMD, identifying CASP4/11 as a promising drug target for treatment and prevention of severe COVID-19.

Immunotherapy has become increasingly important in the treatment of colorectal cancer (CRC). Currently, CD73, also known as ecto-5'-nucleotidase (NT5E), has gained considerable interest as a potential therapeutic target. CD73 is one of the key enzymes catalyzing the conversion of extracellular ATP into adenosine, which in turn exerts potent immune suppressive effects. However, the role of CD73 expression on various cell types within the CRC tumor microenvironment remains unresolved. The expression of CD73 on various cell types has been described recently, but the role of CD73 on B-cells in CRC remains unclear. Therefore, we analyzed CD73 on B-cells, especially on tumor-infiltrating B-cells, in paired tumor and adjacent normal tissue samples from 62 eligible CRC patients. The highest expression of CD73 on tumor-infiltrating B-cells was identified on class-switched memory B-cells, followed by naive B-cells, whereas no CD73 expression was observed on plasmablasts. Clinicopathological correlation analysis revealed that higher CD73

Zusammenfassung Hintergrund Das chirurgische Vorgehen beim kolorektalen Karzinom (KRK) in der Palliativsituation lässt sich nur unzureichend standardisieren. Die vorliegende Studie wurde zur Identifikation von Kriterien für den Entscheid hinsichtlich Resektion des Malignoms mit oder ohne primäre Anastomose initiiert. Patienten/Material und Methoden In einer unizentrischen retrospektiven Analyse wurden 103 Patienten nach palliativer Resektion eines KRK mit oder ohne zeitgleiche Anastomose untersucht. Durch univariate und logistische Regressionsanalyse erfolgte die Beurteilung des Einflusses von insgesamt 40 Faktoren auf die postoperative Morbidität und Mortalität. Ergebnisse In 46 Fällen wurde eine Darmresektion mit primärer Anastomose, in 57 Fällen eine Diskontinuitätsresektion durchgeführt. Die postoperative Morbidität betrug insgesamt 44,7%, die Letalität 17,5%. Nach einzeitiger Resektion und Anastomose erhöhte ein Nikotinabusus (OR 4,2; p = 0,044), eine Hypalbuminämie (OR 4,0; p = 0,012), eine Kachexie (OR 3,9; p = 0,034), ein ASA-Score > 2 (OR 3,7; p = 0,030) und ein(e) Leberumbau/-zirrhose (OR 3,6; p = 0,031) das Risiko für postoperative Komplikationen. Die Hypalbuminämie (OR 1,8; p = 0,036), Kachexie (OR 1,8; p = 0,043), Anämie (OR 1,5; p = 0,038) und ein bekannter Alkoholabusus (OR 1,9; p = 0,023) wurden als unabhängige Risikofaktoren für die frühpostoperative Mortalität identifiziert. Nach Diskontinuitätsresektion führten eine Niereninsuffizienz (OR 2,1; p = 0,042) und Kachexie (OR 1,5; p = 0,045) zum signifikanten Anstieg des Risikos für die postoperative Morbidität, ein Alkoholabusus (OR 1,8; p = 0,041) für die Letalität. Eine Hypalbuminämie (OR 2,8; p = 0,019) und ein ASA-Score > 2 (OR 2,6; p = 0,004) steigerten nach Resektion und Rekonstruktion das Risiko für Majorkomplikationen entsprechend Clavien-Dindo, eine vorbestehende Niereninsuffizienz (OR 1,6; p = 0,023) das Risiko nach Diskontinuitätsresektion. In der univariaten Analyse wurden nach Tumorresektion und Rekonstruktion zusätzlich noch ein ASA-Score > 2 (p = 0,038), in beiden Gruppen mit und ohne primäre Anastomose eine dringliche Operation als signifikante Parameter mit Einfluss auf die Letalität ermittelt (p = 0,010 und p = 0,017). Schlussfolgerung Palliative Resektionen kolorektaler Karzinome haben eine hohe Morbidität und Mortalität. Bei vorbestehendem Alkoholabusus und dringlicher Operationsindikation sollte ein intensiveres Monitoring erfolgen. Bei Anämie, Kachexie, Hypalbuminämie sowie ASA-Score > 2 stellt möglicherweise die Diskontinuitätsresektion den geeigneteren Eingriff dar.

Journal of synchrotron radiation 27(4), 1059 - 1068 (2020). doi:10.1107/S1600577520006864, X-ray imaging is a complementary method to electron and fluorescence microscopy for studying biological cells. In particular, scanning small-angle X-ray scattering provides overview images of whole cells in real space as well as local, high-resolution reciprocal space information, rendering it suitable to investigate subcellular nanostructures in unsliced cells. One persisting challenge in cell studies is achieving high throughput in reasonable times. To this end, a fast scanning mode is used to image hundreds of cells in a single scan. A way of dealing with the vast amount of data thus collected is suggested, including a segmentation procedure and three complementary kinds of analysis, i.e. characterization of the cell population as a whole, of single cells and of different parts of the same cell. The results show that short exposure times, which enable faster scans and reduce radiation damage, still yield information in agreement with longer exposure times., Published by Wiley-Blackwell, [S.l.]

Cryogenic bypass diodes have been installed in all superconducting dipole magnets (1232) and quadrupole magnets (392) of the Large Hadron Collider (LHC) at CERN, and operated during the physics runs since 2009. The bypass diodes are a fundamental ingredient of the quench protection system for those main dipoles and quadrupoles magnets. The diodes are located inside the magnet cryostats, operating in superfluid helium and exposed to ionizing radiation. The connection between the superconducting magnet and the bypass diode is made through a mechanical clamping system and copper bus bars. Since their first installation, all LHC diodes have undergone at least two full thermal cycles (from 1.9 K to room temperature and back to superfluid helium temperature). The evolution of electrical parameters as well as improvements and modifications made over a period of 10 years are reviewed in this paper. With CERN preparing for LHC's High Luminosity era, the long-term strategy for cold diodes is presented, based on the overall results and experience gathered so far, including the studies related to the tolerance with respect to the radiation doses and neutron fluences expected.

The complete understanding of the formation of seemingly levitating droplets on liquid-repelling surfaces provides the basis for further development of applications requiring friction-free liquid transport. For the investigation of these droplets and, thereby, the underlying surface properties, standard techniques typically only reveal a fraction of droplet or surface information. Here, we propose to exploit the light-shaping features of liquid droplets when interpreted as thick biconvex elliptical lenses. This approach has the potential to decode a plethora of droplet information from a passing laser beam, by transforming the information into a structured light field. Here, we explore this potential by analyzing the three-dimensional intensity structures sculpted by the droplet lenses, revealing the transfer of the characteristics of the underlying liquid-repelling effect onto the light field. As illustrative complementary examples, we study droplet lenses formed on a non-wetting Taro (Colocasia esculenta) leaf surface and by the Leidenfrost effect on a heated plate. Our approach may reveal even typically "invisible" droplet properties as the refractive index or internal flow dynamics and, hence, will be of interest to augment conventional tools for droplet and surface investigation.

ATAD2 is an epigenetic bromodomain-containing target which is overexpressed in many cancers and has been suggested as a potential oncology target. While several small molecule inhibitors have been described in the literature, their cellular activity has proved to be underwhelming. In this work, we describe the identification of a novel series of ATAD2 inhibitors by high throughput screening, confirmation of the bromodomain region as the site of action, and the optimization campaign undertaken to improve the potency, selectivity, and permeability of the initial hit. The result is compound