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Abstract High-power tunable lasers are intensely pursued due to their vast application potential such as in telecom, ranging, and molecular sensing. Integrated photonics, however, is usually considered not suitable for high-power applications mainly due to its small size which limits the energy storage capacity and, therefore, the output power. In the late 90s, to improve the beam quality and increase the stored energy, large-mode-area (LMA) fibers were introduced in which the optical mode area is substantially large. Such LMA fibers have transformed the high-power capability of fiber systems ever since. Introducing such an LMA technology at the chip-scale can play an equally disruptive role with high power signal generation from an integrated photonics system. To this end, in this work we demonstrate such a technology, and show a very high-power tunable laser with the help of a silicon photonics based LMA power amplifier. We show output power reaching 1.8 W over a tunability range of 60 nm, spanning from 1.83 µm to 1.89 µm, limited only by the seed laser. Such an integrated LMA device can be used to substantially increase the power of the existing integrated tunable lasers currently limited to a few tens of milliwatts. The power levels demonstrated here reach and surpass that of many benchtop systems which truly makes the silicon photonics based integrated LMA device poised towards mass deployment for high power applications without relying on benchtop systems.

Abstract Femtosecond laser pulses enable the synthesis of light across the electromagnetic spectrum and provide access to ultrafast phenomena in physics, biology, and chemistry. Chip-integration of femtosecond technology could revolutionize applications such as point-of-care diagnostics, bio-medical imaging, portable chemical sensing, or autonomous navigation. However, current chip-integrated pulse sources lack the required peak power, and on-chip amplification of femtosecond pulses has been an unresolved challenge. Here, addressing this challenge, we report >50-fold amplification of 1 GHz-repetition-rate chirped femtosecond pulses in a CMOS-compatible photonic chip to 800 W peak power with 116 fs pulse duration. This power level is 2–3 orders of magnitude higher compared to those in previously demonstrated on-chip pulse sources and can provide the power needed to address key applications. To achieve this, detrimental nonlinear effects are mitigated through all-normal dispersion, large mode-area and rare-earth-doped gain waveguides. These results offer a pathway to chip-integrated femtosecond technology with peak power levels characteristic of table-top sources.

We present a genome assembly from an individual male Platypus cylindrus (the oak pinhole borer; Arthropoda; Insecta; Coleoptera; Curculionidae). The genome sequence is 147.5 megabases in span. Most of the assembly is scaffolded into 8 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 19.29 kilobases in length. Gene annotation of this assembly on Ensembl identified 13,468 protein coding genes.

We present a genome assembly from an individual female Lochmaea capreae (the willow leaf beetle; Arthropoda; Insecta; Coleoptera; Chrysomelidae). The genome sequence is 534.7 megabases in span. Most of the assembly is scaffolded into 17 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 18.85 kilobases in length. Gene annotation of this assembly on Ensembl identified 12,254 protein coding genes.

We present a genome assembly from an individual Cow Parsley Leaf Beetle Chrysolina oricalcia (the Cow Parsley Leaf Beetle; Arthropoda; Insecta; Coleoptera; Chrysomelidae). The genome sequence is 1,423.4 megabases in span. Most of the assembly is scaffolded into 22 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 16.93 kilobases in length. Gene annotation of this assembly on Ensembl identified 35,990 protein coding genes.

We present a genome assembly from an individual male Platypus cylindrus (the oak pinhole borer; Arthropoda; Insecta; Coleoptera; Curculionidae). The genome sequence is 147.5 megabases in span. Most of the assembly is scaffolded into 8 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 19.29 kilobases in length. Gene annotation of this assembly on Ensembl identified 13,468 protein coding genes.

Abstract Annexins are cytosolic proteins with conserved three-dimensional structures that bind acidic phospholipids in cellular membranes at elevated Ca2+ levels. Through this they act as Ca2+-regulated membrane binding modules that organize membrane lipids, facilitating cellular membrane transport but also displaying extracellular activities. Recent discoveries highlight annexins as sensors and regulators of cellular and organismal stress, controlling inflammatory reactions in mammals, environmental stress in plants, and cellular responses to plasma membrane rupture. Here, we describe the role of annexins as Ca2+-regulated membrane binding modules that sense and respond to cellular stress and share our view on future research directions in the field.

We present a genome assembly from an individual male Bruchidius siliquastri (the Judas tree Seed Beetle; Arthropoda; Insecta; Coleoptera; Chrysomelidae). The genome sequence is 375.6 megabases in span. Most of the assembly is scaffolded into 11 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 15.81 kilobases in length. Gene annotation of this assembly on Ensembl identified 17,940 protein coding genes.

The species of the subgenus Stichoptera occurring in Switzerland are revised, based on a combination of literature data, old museum specimens and recent material. Four species, one with two subspecies, Chrysolina kuesteri (Helliesen, 1912), Ch. latecincta latecincta (Demaison, 1896), Ch. latecincta norica (Holdhaus, 1914), Ch. rossia (Illiger, 1802) and Ch. sanguinolenta (Linnaeus, 1758) are confirmed to occur in Switzerland, while Ch. gypsophilae (Küster, 1845) has to be excluded from the Swiss fauna due to insufficient evidence. Errors and unclarities in the older literature are discussed. Ch. kuesteri was found abundantly in central Valais, allowing some notes on its larval biology. Larvae of the alpine Ch. latecincta are also illustrated, along with notes on its habitat and some past and present distribution records. Illustrations for all Swiss members of the subgenus, as well as distribution maps with all confirmed records, are provided.

Wastewater surveillance for SARS-CoV-2 has been demonstrated to be a valuable tool in monitoring community-level virus circulation and assessing new outbreaks. It may become a useful tool in the early detection and response to future pandemics, enabling public health authorities to implement timely interventions and mitigate the spread of infectious diseases with the fecal excretion of their agents. It also offers a chance for cost-effective surveillance. Reverse transcription-quantitative polymerase chain reaction (RTqPCR) is the most commonly used method for viral RNA detection in wastewater due to its sensitivity, reliability, and widespread availability. However, recent studies have indicated that reverse transcription droplet digital PCR (RTddPCR) has the potential to offer improved sensitivity and accuracy for quantifying SARS-CoV-2 RNA in wastewater samples. In this study, we compared the performance of RTqPCR and RTddPCR approaches for SARS-CoV-2 detection and quantification on wastewater samples collected during the third epidemic wave in Saxony, Germany, characterized by low-incidence infection periods. The determined limits of detection (LOD) and quantification (LOQ) were within the same order of magnitude, and no significant differences were observed between the PCR approaches with respect to the number of positive or quantifiable samples. Our results indicate that both RTqPCR and RTddPCR are highly sensitive methods for detecting SARS-CoV-2. Consequently, the actual gain in sensitivity associated with ddPCR lags behind theoretical expectations. Hence, the choice between the two PCR methods in further environmental surveillance programs is rather a matter of available resources and throughput requirements.

Low phase-noise THz wave generation is in high demand for applications such as wireless communications and radars. Here, the authors generate low-noise THz waves via photodetection of the carrier of a Kerr frequency comb, which is repetition-rate stabilized using a two-wavelength delayed self-heterodyne interferometer.

We present a genome assembly from an individual male Pterostichus niger (a ground beetle; Arthropoda; Insecta; Coleoptera; Carabidae). The genome sequence is 674.1 megabases in span. Most of the assembly is scaffolded into 19 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 17.16 kilobases in length.

We present a genome assembly from an individual male Cantharis rufa (soldier beetle; Arthropoda; Insecta; Coleoptera; Cantharidae). The genome sequence is 355.3 megabases in span. Most of the assembly is scaffolded into 7 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 17.34 kilobases in length.

We present a genome assembly from an individual Cow Parsley Leaf Beetle Chrysolina oricalcia (the Cow Parsley Leaf Beetle; Arthropoda; Insecta; Coleoptera; Chrysomelidae). The genome sequence is 1,423.4 megabases in span. Most of the assembly is scaffolded into 22 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 16.93 kilobases in length. Gene annotation of this assembly on Ensembl identified 35,990 protein coding genes.

The European Community (EC), afraid of lagging behind the United States and Japan in the technology race, developed a series of strategies in the 1980s and 1990s to enhance their position in the field of information and telecommunication technologies (ICT). One key strategy was the training and retraining of citizens to deal with the shortage of a highly skilled labor force. At the same time, women’s issues were being raised as part of the EC’s political agenda, with a particular emphasis on the effects of technological change on the employment of women. We claim that despite the advantageous conditions for promoting women’s advanced education in ICT, the EC’s strategy was to promote only basic computer literacy, following a discourse that victimized women, due to their alleged lack of skills and flexibility. Although by the late 1980s, the view of women as constituting potential economic assets in the EC’s economy became more prominent, the concrete measures for women’s education and training did not substantially change and remained scantily funded and short-sighted throughout the whole period.

Vancomycin-resistant (VR) Enterococcus spp. can be detected in high concentrations in wastewaters and pose a risk to public health. During a one-year study (September 2022–August 2023), 24 h composite raw wastewater samples (n = 192) of a municipal wastewater treatment plant were investigated for cultivable enterococci. After growth on Slanetz–Bartley agar (SBA), a mean concentration of 29,736 ± 9919 cfu/mL was calculated. Using MALDI-TOF MS to characterize randomly picked colonies (n = 576), the most common species were found to be Enterococcus faecium (72.6%), E. hirae (13.7%), and E. faecalis (8.0%). Parallel incubation of wastewater samples on SBA and VRESelect agar resulted in a mean rate of VR enterococci of 2.0 ± 1.5%. All the tested strains grown on the VRESelect agar (n = 172) were E. faecium and carried the vanA (54.6%) or vanB gene (45.4%) with limited sequence differences. In susceptibility experiments, these isolates showed a high-level resistance to vancomycin (>256 µg/mL). Concentration of vancomycin was determined in 93.7% of 112 wastewater samples (mean: 123.1 ± 64.0 ng/L) and varied between below 100 ng/L (the detection limit) and 246.6 ng/L. A correlation between the concentration of vancomycin and the rate of VR strains among the total enterococci could not be found. The combination of incubation of samples on SBA and a commercial vancomycin-containing agar applied in clinical microbiology with a multiplex PCR for detection of van genes is an easy-to-use tool to quantify and characterize VR Enterococcus spp. in water samples.

We present a genome assembly from an individual male Philonthus cognatus (a rove beetle; Arthropoda; Insecta; Coleoptera; Staphylinidae). The genome sequence is 1,030.6 megabases in span. Most of the assembly is scaffolded into 12 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 20.7 kilobases in length. Gene annotation of this assembly on Ensembl identified 29,629 protein coding genes.

This article examines how and why elementary and lower secondary school teachers in Switzerland constructed audio-visual media as educational devices. The new technical solutions had to be interpreted and adapted so that they could be considered educational. The educational press and internal minutes of the Swiss Teachers’ Association SLV show the public discussions as well as internal conflicts. They allow conclusions to be drawn about the role of the teacher association in constructing educational media. They also show the part played by political and practical issues in the evaluation and development of educational media. The article ends with a conclusion that outlines the different ways in which Swiss elementary and lower secondary school teachers dealt with new teaching media.

An updated checklist of the Swiss species belonging to the families Cantharidae and Lycidae, is presented and briefly discussed. This checklist includes 106 species and is based on over 26’000 occurrences obtained from the identification of specimens held in museum and private collections, as well as from records taken from the literature. Cantharis liburnica Depoli, 1912, C. paradoxa Hicker, 1960, Malthinus rubricollis Baudi di Selve, 1859 and Malthodes umbrosus Kiesenwetter, 1871 are recorded from Switzerland for the first time. Two species previously recorded from Switzerland (Malthodes montanus Kiesenwetter, 1863, M. boicus Kiesenwetter, 1863) are excluded from this list, as those records were based on misidentified material.

Whereas the Austrian Government after an initial period of controversies quickly took the position that the Republic of Austria continued to exist throughout the period of Austria’s incorporation into Hitlerite Germany, the Allied Powers preferred a pragmatic approach through the Moscow Declaration of 1943 and the Treaty of Vienna of 1955. They allowed the Austrian Government to act on the grounds of the so-called “Occupation Theory”, but bound it to international commitments, which followed from an understanding that Austria also shared the responsibility for the acts of warfare by Hitler’s Germany. Thus, they combined the elements of theories of discontinuity (fusion/annexation) with the elements of the theory of occupation.

Abstract Background Due to clinical and methodological diversity, clinical studies included in meta-analyses often differ in ways that lead to differences in treatment effects across studies. Meta-regression analysis is generally recommended to explore associations between study-level characteristics and treatment effect, however, three key pitfalls of meta-regression may lead to invalid conclusions. Our aims were to determine the frequency of these three pitfalls of meta-regression analyses, examine characteristics associated with the occurrence of these pitfalls, and explore changes between 2002 and 2012. Methods A meta-epidemiological study of studies including aggregate data meta-regression analysis in the years 2002 and 2012. We assessed the prevalence of meta-regression analyses with at least 1 of 3 pitfalls: ecological fallacy, overfitting, and inappropriate methods to regress treatment effects against the risk of the analysed outcome. We used logistic regression to investigate study characteristics associated with pitfalls and examined differences between 2002 and 2012. Results Our search yielded 580 studies with meta-analyses, of which 81 included meta-regression analyses with aggregated data. 57 meta-regression analyses were found to contain at least one pitfall (70%): 53 were susceptible to ecological fallacy (65%), 14 had a risk of overfitting (17%), and 5 inappropriately regressed treatment effects against the risk of the analysed outcome (6%). We found no difference in the prevalence of meta-regression analyses with methodological pitfalls between 2002 and 2012, nor any study-level characteristic that was clearly associated with the occurrence of any of the pitfalls. Conclusion The majority of meta-regression analyses based on aggregate data contain methodological pitfalls that may result in misleading findings.

Key steps towards photonic interposers for integrated optical synthesizers are shown: filters, mixers, linear processing of an octave-spanning microcomb, integration of microcomb and interposer layers, and a system-level feasibility analysis.

Discodon tricolor (Guérin-Méneville, 1832) was thought to be a common species widely distributed in the Atlantic Forests of Brazil, yet showing morphological and chromatic variations. After examination of a large number of specimens from different regions of the Atlantic Forest biome, we found that Discodon tricolor actually represents a complex of many similar and sometimes sympatric species. Thirteen species in this complex are recognised as valid: Discodon tricolor, D. neoteutonum sp. nov., D. vanini sp. nov., D. obscurior Pic, 1906 stat. nov., D. lineaticorne sp. nov., D. aurimaculatum sp. nov., D. marginicolle sp. nov., D. tenuecostatum sp. nov., D. nigrocephalum Pic, 1949, D. tamoio sp. nov., D. viridimontanum sp. nov., D. crassipes Wittmer, 1952, and D. testaceipes Pic, 1930 stat. nov. The species Discodon albonotatum Pic, 1906 is confirmed as a synonym of D. tricolor, while the subspecies D. albonotatum obscurior and D. albonotatum testaceipes are elevated to specific status. The subgenus Acanthodiscodon Wittmer, 1952 is synonymised with Discodon Gorham, 1881. All the species are described and illustrated in detail and an identification key is provided. Despite being chromatically similar, the species show major morphological differences in their aedeagus and antennal structures, suggesting that they do not form a monophyletic clade. A potential mimicry ring involving these species of Discodon as well as other members of Cantharidae, Lampyridae, Cerambycidae and Belidae is discussed. Comments are made on the conservation of these species and their habitats within the Atlantic Forest biome.

In the following I would like to expose Julian Culp’s normative argumentation to some empirical considerations. My commentary focuses on one of the central premises of the book: Culp assumes that education can make a decisive contribution to solving the current challenges in plural and globalized societies. He states that recent political philosophy has unacceptably neglected the issue of education. But the book’s aim is not the theoretical determination of education itself. Rather, Culp is concerned with the question of giving education the right normative foundation to solve the social, ecological and democratic challenges the globalized world is currently facing. I don’t think that one can or should discuss and analyse education without normative considerations. Educational thinking cannot do without a normative foundation and it is helpful and necessary to reflect upon them philosophically. This is the central concern of the book, and there is nothing to be added to it by historians or educational researchers. But a purely normative approach runs the risk of repeating many of the problems inherent in educational thinking. I think that even a normative approach would gain a lot from taking the empirical and historical boundaries of its subject more seriously than Culp does. Therefore, most of my remarks are about the relationship between normative theory and historical realities.

Zusammenfassung Dieser Artikel rekonstruiert die Veränderungen in der politischen Ökonomie der Schweizer Erwachsenenbildung seit Mitte des 20. Jahrhunderts. Methodisch stützt sich die Analyse auf den historischen Institutionalismus und konzentriert sich damit auf Pfadabhängigkeiten und sogenannte „critical junctures“. Im Folgenden wird gezeigt, dass die Entwicklung des Weiterbildungssystems in der Schweiz weder allein korporatistischen noch ausschließlich Marktprinzipien folgt. Vielmehr wird gezeigt, dass die gegenwärtige Situation nicht ohne Berücksichtigung der verschiedenen nationalen Initiativen im Kontext des digitalen Wandels seit den 1970er Jahren sowie der Arbeit des Schweizerischen Verbands für Weiterbildung SVEB verstanden werden kann. Der Artikel schließt mit Überlegungen zu den erwarteten Auswirkungen des ersten nationalen Weiterbildungsgesetzes, das 2017 in Kraft getreten ist.

In this viewpoint we make specific recommendations that can assist and make the return to sport/exercise as safe as possible for all those impacted – from the recreational athlete to the elite athlete. We acknowledge that there are varying rules and regulations around the world, not to mention the varying philosophies and numerous schools of thought as it relates to return to sport/exercise and we have been cognisant of this in our recommendations. Despite the varying rules and circumstances around the world, we believe it is essential to provide some helpful and consistent guidance for return to training and sport for sport and exercise physicians around the world at this most difficult time. The present viewpoint provides practical and medical recommendations on the resumption to sport process.

Abstract Background Preclinical studies demonstrate synergism between cancer immunotherapy and local radiation, enhancing anti-tumor effects and promoting immune responses. BI1361849 (CV9202) is an active cancer immunotherapeutic comprising protamine-formulated, sequence-optimized mRNA encoding six non-small cell lung cancer (NSCLC)-associated antigens (NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, and MUC-1), intended to induce targeted immune responses. Methods We describe a phase Ib clinical trial evaluating treatment with BI1361849 combined with local radiation in 26 stage IV NSCLC patients with partial response (PR)/stable disease (SD) after standard first-line therapy. Patients were stratified into three strata (1: non-squamous NSCLC, no epidermal growth factor receptor (EGFR) mutation, PR/SD after ≥4 cycles of platinum- and pemetrexed-based treatment [n = 16]; 2: squamous NSCLC, PR/SD after ≥4 cycles of platinum-based and non-platinum compound treatment [n = 8]; 3: non-squamous NSCLC, EGFR mutation, PR/SD after ≥3 and ≤ 6 months EGFR-tyrosine kinase inhibitor (TKI) treatment [n = 2]). Patients received intradermal BI1361849, local radiation (4 × 5 Gy), then BI1361849 until disease progression. Strata 1 and 3 also had maintenance pemetrexed or continued EGFR-TKI therapy, respectively. The primary endpoint was evaluation of safety; secondary objectives included assessment of clinical efficacy (every 6 weeks during treatment) and of immune response (on Days 1 [baseline], 19 and 61). Results Study treatment was well tolerated; injection site reactions and flu-like symptoms were the most common BI1361849-related adverse events. Three patients had grade 3 BI1361849-related adverse events (fatigue, pyrexia); there was one grade 3 radiation-related event (dysphagia). In comparison to baseline, immunomonitoring revealed increased BI1361849 antigen-specific immune responses in the majority of patients (84%), whereby antigen-specific antibody levels were increased in 80% and functional T cells in 40% of patients, and involvement of multiple antigen specificities was evident in 52% of patients. One patient had a partial response in combination with pemetrexed maintenance, and 46.2% achieved stable disease as best overall response. Best overall response was SD in 57.7% for target lesions. Conclusion The results support further investigation of mRNA-based immunotherapy in NSCLC including combinations with immune checkpoint inhibitors. Trial registration ClinicalTrials.gov identifier: NCT01915524.

Abstract Background Even clearly resectable pancreatic cancer still has an unfavorable prognosis. Neoadjuvant or perioperative therapies might improve the prognosis of these patients. Thus, evaluation of perioperative chemotherapy in resectable pancreatic cancer in a prospective, randomized trial is warranted. A substantial improvement in overall survival of patients with metastatic pancreatic cancer with FOLFIRINOX and nab-paclitaxel/gemcitabine vs standard gemcitabine has been demonstrated in phase III-trials. Indeed nab-paclitaxel/gemcitabine has a more favorable toxicity profile compared to the FOLFIRINOX protocol and appears applicable in a perioperative setting. Methods NEONAX is an interventional, prospective, randomized, controlled, open label, two sided phase II study with an unconnected analysis of the results in both experimental arms against a fixed survival probability (38% at 18 months with adjuvant gemcitabine), NCT02047513. NEONAX will enroll 166 patients with resectable pancreatic ductal adenocarcinoma (≤ cT3, N0 or N1, cM0) in two arms: Arm A (perioperative arm): 2 cycles nab-paclitaxel (125 mg/m2)/gemcitabine (1000 mg/m2, d1, 8 and 15 of an 28 day-cycle) followed by tumor surgery followed by 4 cycles nab-paclitaxel/gemcitabine, Arm B (adjuvant arm): tumor surgery followed by 6 cycles nab-paclitaxel/gemcitabine. The randomization (1:1) is eminent to avoid allocation bias between the groups. Randomization is stratified for tumor stage (ct1/2 vs. cT3) and lymph node status (cN0 vs. cN1). Primary objective is disease free survival (DFS) at 18 months after randomization. Key secondary objectives are 3-year overall survival (OS) rate and DFS rate, progression during neoadjuvant therapy, R0 and R1 resection rate, quality of life and correlation of DFS, OS and tumor regression with pharmacogenomic markers, tumor biomarkers and molecular analyses (ctDNA, transcriptome, miRNA-arrays). In addition, circulating tumor-DNA will be analyzed in patients with the best and the worst responses to the neoadjuvant treatment. The study was initiated in March 2015 in 26 centers for pancreatic surgery in Germany. Discussion The NEONAX trial is an innovative study on resectable pancreatic cancer and currently one of the largest trials in this field of research. It addresses the question of the role of intensified perioperative treatment with nab-paclitaxel plus gemcitabine in resectable pancreatic cancers to improve disease-free survival and offers a unique potential for translational research. Trial registration ClinicalTrials.gov: NCT02047513, 08/13/2014.

Soft tissue infections in open fractures or burns are major cause for high morbidity in trauma patients. Sustained, long-term and localized delivery of antimicrobial agents is needed for early eradication of these infections. Traditional (topical or systemic) antibiotic delivery methods are associated with a variety of problems, including their long-term unavailability and possible low local concentration. Novel approaches for antibiotic delivery via wound coverage/healing scaffolds are constantly being developed. Many of these approaches are associated with burst release and thus seldom maintain long-term inhibitory concentrations. Using 3D core/shell extrusion printing, scaffolds consisting of antibiotic depot (in the core composed of low concentrated biomaterial ink 3% alginate) surrounded by a denser biomaterial ink (shell) were fabricated. Denser biomaterial ink (composed of alginate and methylcellulose or alginate, methylcellulose and Laponite) retained scaffold shape and modulated antibiotic release kinetics. Release of antibiotics was observed over seven days, indicating sustained release characteristics and maintenance of potency. Inclusion of Laponite in shell, significantly reduced burst release of antibiotics. Additionally, the effect of shell thickness on release kinetics was demonstrated. Amalgamation of such a modular delivery system with other biofabrication methods could potentially open new strategies to simultaneously treat soft tissue infections and aid wound regeneration.

Abstract This article is concerned with the discourse and policy of lifelong learning in Europe after 1973. It deals with the question whether the 1980s have to be seen as a period of diminishing interest in lifelong learning or as a formative phase of so called neoliberalism. Applying a corpus lingustic approach, it analyses the official documents of the European Communities as archived in the database EUR-Lex. The results are interpreted as the expression of a new European governance regime called “technology corporatism” (Bornschier), which was jointly supported by supranational political actors, large-scale industry and science and also affected their understanding of lifelong learning.

Resection of colorectal liver metastases (CRLM) is a potential curative treatment for patients with metastatic colorectal cancer (mCRC) with liver-limited disease (LLD). Although long-term survival improved considerably within the last decades, high recurrence rates of 50-75% after resection remain a major challenge.Tecemotide (L-BLP25) is an antigen-specific cancer vaccine inducing immunity against mucin-1 (MUC1). The LICC trial aimed to improve survival in patients with mCRC after R0/R1 resection of CRLM. LICC was a binational, randomized, double-blind, placebo-controlled, multicenter phase 2 study including patients with R0/R1 resected CRLM without evidence of metastatic disease outside the liver. Co-primary endpoints were recurrence-free survival (RFS) and 3-year overall survival (OS) rate, secondary endpoints were RFS and OS in subgroups with different MUC1 expression and safety. In total, 121 patients were 2:1 randomized between Oct 2011 and Dec 2014to receive tecemotide (N=79) or placebo (N=42). Baseline characteristics were well balanced. Median RFS was 6.1 months (95% CI 4.5-8.9) and 11.4 months (95% CI 3.7-21.2) (P = .1754), 3-year OS rate 69.1% and 79.1%, median OS 62.8 months and not reached in the tecemotide vs. placebo arm (P = .2141), respectively. Cox regression models revealed no dependence of RFS or OS on MUC1 expression. The most common tecemotide-related grade 3/4 adverse events were diarrhea, injection site reaction, intestinal perforation, peritonitis and tinnitus (1.3% each). The LICC trial failed to meet its primary endpoints of significantly improving RFS and OS with tecemotide. However, both arms showed unexpectedly long OS. MUC1 expression was not associated with outcome. EudraCT No: 2011–000218-20 Clinical Trial Information: NCT01462513 Financial Support: Merck KGaA, Darmstadt, Germany Abbreviations: AE: adverse event; CP: cyclophosphamide; CRC: colorectal cancer; CT: computed tomography; ECOG: Eastern Cooperative Oncology Group; FU: follow-up; HR: hazard ratio; IHC: immunohistochemical staining; ITT: intention-to-treat; DSMB: Data Safety Monitoring Board; LLD: liver-limited disease; mCRC: metastatic colorectal cancer; MPLA: monophosphoryl lipid; AMRI: magnetic resonance imaging; MUC1: mucin 1; NA: not applicable; NCI-CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events; NS: normal saline; NSCLC: non-small-cell lung carcinoma; OS: overall surviva; lPP: per protocol; RAS: Rat sarcoma; RFS: recurrence-free survival; TEAE: treatment-emergent adverse event; UICC: Union for International Cancer Control; US: ultrasound; vs.: versus.

Natural history collections provide an invaluable basis for systematics, ecology, and conservation. Besides being an important source of DNA, museum specimens may also contain a plethora of natural products. Especially, dried insect collections represent a global repository with billions of inventoried vouchers. Due to their vast diversity, insects possess a great variety of defensive compounds, which they either produce autogenously or derive from the environment. Here, we present a case study on fireflies (Coleoptera: Lampyridae), which produce bufadienolides as a defense against predators. These toxins belong to the cardiotonic steroids, which are used for the treatment of cardiac diseases and specifically inhibit the animal enzyme Na+/K+-ATPase. Bufadienolides have been reported from only seven out of approximately 2000 described firefly species. Using a non-destructive approach, we screened 72 dry coleopteran specimens for bufadienolides using HPLC-DAD and HPLC-MS. We found bufadienolides including five novel compounds in 21 species of the subfamily Lampyrinae. The absence of bufadienolides in the phylogenetically related net-winged beetles (Lycidae) and the lampyrid subfamilies Luciolinae and Lamprohizinae indicates a phylogenetic pattern of bufadienolide synthesis. Our results emphasize the value of natural history collections as an archive of chemical information for ecological and evolutionary basic research and as an untapped source for novel bioactive compounds.