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The food system represents a key industry for Europe and particularly Germany. However, it is also the single most significant contributor to climate and environmental change. A food system transformation is necessary to overcome the system's major and constantly increasing challenges in the upcoming decades. One possible facilitator for this transformation are radical and disrup-tive innovations that start-ups develop. There are many challenges for start-ups in general and food start-ups in particular. Various support opportunities and resources are crucial to ensure the success of food start-ups. One aim of this study is to identify how the success of start-ups in the food system can be supported and further strengthened by players in the innovation ecosystem in Germany. There is still room for improvement and collaboration toward a thriving innovation ecosystem. A successful innovation ecosystem is characterised by a well-organised, collaborative, and supportive environment with a vivid exchange between the members in the ecosystem. The interviewees confirmed this, and although the different actors are already cooperating, there is still room for improvement. The most common recommendation for improving cooperation is learning from other countries and bringing the best to Germany.

Background & Aims Based on positive results from small single center studies, granulocyte-colony stimulating factor (G-CSF) is being widely used for the treatment of patients with acute-on-chronic liver failure (ACLF). Herein, we aimed to evaluate the safety and efficacy of G-CSF in patients with ACLF. Methods In this multicenter, prospective, controlled, open-label phase II study, 176 patients with ACLF (EASL-CLIF criteria) were randomized to receive G-CSF (5 μg/kg daily for the first 5 days and every third day thereafter until day 26) plus standard medical therapy (SMT) (n = 88) or SMT alone. The primary efficacy endpoint was 90-day transplant-free survival analyzed by Cox regression modeling. The key secondary endpoints were overall and transplant-free survival after 360 days, the development of ACLF-related complications, and the course of liver function scores during the entire observation period. Results Patients treated with G-CSF had a 90-day transplant-free survival rate of 34.1% compared to 37.5% in the SMT group (hazard ratio [HR] 1.05; 95% CI 0.711–1.551; p = 0.805). Transplant-free and overall survival at 360 days did not differ between the 2 arms (HR 0.998; 95% CI 0.697–1.430; p = 0.992 and HR 1.058; 95% CI 0.727–1.548; p = 0.768, respectively). G-CSF did not improve liver function scores, the occurrence of infections, or survival in subgroups of patients without infections, with alcohol-related ACLF, or with ACLF defined by the APASL criteria. Sixty-one serious adverse events were reported in the G-CSF+SMT group and 57 were reported in the SMT group. In total, 7 drug-related serious adverse reactions occurred in the G-CSF group. The study was prematurely terminated due to futility after conditional power calculation. Conclusions In contrast to previous findings, G-CSF had no significant beneficial effect on patients with ACLF in this multicenter controlled trial, which suggests that it should not be used as a standard treatment for ACLF. ClinicalTrials.gov number NCT02669680 Lay summary Granulocyte-colony stimulating factor was considered as a novel treatment for acute-on-chronic liver failure (ACLF). We performed the first randomized, multicenter, controlled phase II trial, which showed that G-CSF did not improve survival or other clinical endpoints in patients with ACLF. Therefore, G-CSF should not be used to treat liver disease outside clinical studies.

In the decades following World War II, British cities—and, to a lesser degree, rural areas—underwent radical architectural and structural transformations. Yet, architecture associated with post-war reconstruction is significantly underrepresented in children’s picture books of the period. The home, the street, and the high-street are, more often than not, depicted in a formal language associated with Georgian, Edwardian and Victorian architectural ideals. This paper explores what kind of cultural ideologies children are integrated into when it comes to the representation of post-war architecture. Specifically, the paper focuses on domestic space and asks what ideas of the ‘home’ are promoted. Drawing on Gaston Bachelard’s exploration of the relationship between domestic architecture and emotional/psychological response in The Poetics of Space (1957), and Jean Baudrillard’s theory of communication in the age of postmodernity, this paper maps the influence of post-war architectural design on a selection of children’s picture books published during the 1960s and 1970s. The paper concludes with an examination of two popular picture books published in 1996 and 2013, which trace the legacies of post-war architecture.

Background Immunotherapy with T cells that were modified by gene-transfer to express a ROR1-specific chimeric antigen receptor (ROR1 CAR-T) has therapeutic potential in ROR1+ malignancies in hematology and oncology. The ROR1 tumor antigen has a favorable expression profile with absence in vital normal human tissues. In this study, we sought to establish and validate clinical-grade manufacturing of ROR1 CAR-T to enable a Phase I/IIa clinical trial. In particular, we sought to integrate virus-free gene-transfer based on Sleeping Beauty transposition into this manufacturing protocol to permit scale-up and export to point-of-care manufacturing, and to reduce turn-around time, complexity and regulatory burden associated with conventional viral gene-transfer (biosafety level 2 to biosafety level 1). Materials and Methods Buffy coats or leukaphereses were obtained from healthy donors to perform protocol optimization (n=7) and scale-up runs (n=1). CD4+ and CD8+ T cells were isolated separately by magnetic selection and stimulated with CD3/CD28 TransACT® reagent. T cells were transfected with mRNA encoding hyperactive Sleeping Beauty transposase (SB100X) and minicircle DNA (MC) encoding a pT2 transposon comprising the ROR1 CAR and an EGFRt marker gene using the MaxCyte GTx ® electroporation platform. Following transfection, T cells were expanded for 10–13 days in G-REX® bioreactors and then harvested and formulated into the drug product at a 1:1 ratio of CAR-expressing CD4:CD8 T cells. The drug product underwent comprehensive phenotypic, functional and genomic analyses as part of product qualification. Results The set of protocol optimization runs resulted in a highly robust process. On average, the stable gene-transfer rate at the end of the manufacturing process was 71% in CD4+ (n=5) and 54% in CD8+ T cells (n=7). The average yield of ROR1 CAR-T relative to the number of input T cells was 12.6-fold for CD4+ and 9.4-fold for CD8+ after 12–15 days of expansion, with an average viability of 84% for CD4+ and 82% of CD8+ T cells. The scale-up run was performed with a leukapheresis product from which 52.5 × 10^6 CD4+ and 109 × 10^6 CD8+ T cells were transfected. At the end of the manufacturing process (day 12), there were 844 × 10^6 CAR-expressing CD4+ (~16-fold expansion) and 857 × 10^6 CAR-expressing CD8+ T cells (8-fold expansion). In functional testing, ROR1 CAR-T showed specific recognition and potent elimination of ROR1+ target cells, as well as antigen-dependent cytokine production and productive proliferation in in vitro analyses. Experiments to determine the anti-tumor potency of the drug product in vivo and detailed genomic analyses are ongoing. Preliminary analyses suggest a favorable genomic insertion profile of the CAR transposon, and a transposon copy number that is well within the range acceptable for clinical use of the drug product. Conclusions With this novel protocol, we aim to obtain the first manufacturing license for CAR-T in Europe that integrates our optimized approach with SB100X mRNA and transposon MC for CAR gene-transfer on the MaxCyte transfection platform. The quality and yield of the drug product support the design and dose escalation of the proposed clinical trial with ROR1 CAR-T, and will serve as a blueprint for other CAR-T products from our pipeline. Disclosure Information K. Mestermann: None. M. Eichler: None. M. Machwirth: None. K. Kebbel: None. U. Kohl: None. H. Einsele: None. C. Muller: None. J. Lehmann: None. T. Rasko: None. F. Lundberg: None. Z. Izsvak: None. G. Schmiedeknecht: None. M. Hudecek: None.

The purpose of this phenomenological study was to discover the effectiveness of curriculum specific to young adults with autism spectrum disorder (ASD) within a specific community. This paper supports a program evaluation of a life skill curriculum compiled, taught and refined, and specifically designed for young adults with ASD. Young adults with ASD have few resources for a successful transition from adolescence to young adulthood. There is diminutive amount of literature evaluating and providing evidence that teaching a life skill curriculum is effective in enhancing success in the transition for young adult with ASD. There is a great deal of information and research on the effectiveness of early treatment but a considerable deficit is found in those clients who did not receive the diagnosis of ASD until they were in late adolescence or early adulthood. The population of young adult clients ranges from low, including non-verbal clients, to high functioning. It is the author's hope to contribute to the gap in the literature with programming and resources to meet the needs, support growth, and the opportunity for reaching the highest level of independence in the ASD population. The growth demonstrated by the clients in the life skill curriculum demonstrated an average of two categories. With the direct supervision and support by the mentors and Life Skill coaches, the clients experienced the feeling of choice and autonomy as each worked toward some form of more independent living.