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Abstract This paper explores the institutional mainstreaming of nature-based solutions (NBS) to advance a process-based understanding about how to strategically develop the governance capacities needed for systemic, localised and inclusive NBS. To this end, it reports how policy officers in ten European cities have started to mainstream NBS by interacting with and changing incumbent governance arrangements when experimenting with novel governance processes and mechanisms to plan, deliver and steward NBS. Based on these activities of the policy officers, the analysis identifies three strategies, associated stepping stones and changes in governance conditions, to mainstream NBS in governance capacities: institutionalising (a) a systems’ approach to link NBS to policies, regulations, and departments across goals and sectors, (b) inclusive collaborations for localised and inclusive interventions, and (c) reflexivity and learning about how NBS interact with the (institutional, ecological, social, etc.) contexts and create impacts. The strategies illustrate institutional entrepreneurship in interacting with incumbent governance contexts, and how starting from NBS as a type of systemic innovation can promote broader shifts in urban governance arrangements.

ABSTRACT The actions of many bacterial toxins depend on their ability to bind to one or more cell-surface receptors. Anthrax toxin acts by a sequence of events that begins when the protective-antigen (PA) moiety of the toxin binds to either one of two cell-surface proteins, ANTXR1 and ANTXR2, and is proteolytically activated. The activated PA self-associates to form oligomeric pore precursors, which, in turn, bind the enzymatic moieties of the toxin and transport them to the cytosol. We introduced a double mutation into domain 4 of PA to ablate its native receptor-binding function and fused epidermal growth factor (EGF) to the C terminus of the mutated protein. The resulting fusion protein transported enzymatic effector proteins into a cell line that expressed the EGF receptor (A431 cells), but not into a line lacking this receptor (CHO-K1 cells). Addition of excess free EGF blocked transport of effector proteins into A431 cells via the fusion protein, but not via native PA. We also showed that fusing the diphtheria toxin receptor-binding domain to the C terminus of the mutated PA channeled effector-protein transport through the diphtheria toxin receptor. PA fusion proteins with altered receptor specificity may be useful in biological research and could have practical applications, including ablation or perturbation of selected populations of cells in vivo. IMPORTANCE Bacterial toxins that act within mammalian cells have receptor-dependent mechanisms to transport their enzymatic components to the cytoplasmic compartment. By inactivating or otherwise modifying their respective intracellular targets, these intracellular effectors disrupt metabolic pathways and in some cases cause death of the cell. Our results show that the receptor specificity of the transport protein of anthrax toxin may be readily changed, raising the possibility that receptor-redirected forms of protective antigen (PA) and PA homologs may be useful for research and medical applications requiring modification or ablation of designated populations of cells.

Background: Proactively monitoring infliximab levels is an emerging area of interest in pediatric Crohn's disease. There are only limited data on therapeutic drug monitoring for children with Crohn's disease. The goal of our study was to determine the utility of therapeutic drug monitoring in achieving clinical remission in a cohort of pediatric Crohn's disease patients receiving infliximab., Methods: This prospective single-center study enrolled 37 patients with Crohn's disease at the start of infliximab infusions and monitored trough levels at 6-month intervals for 18 months. Each participant was matched to a historic control for the modified pediatric Crohn's disease activity index (mPCDAI) at baseline, age and sex. The primary outcome was an mPCDAI score of ≤7.5 at 6, 12 and 18 months. A multivariate logistic regression analysis was performed., Results: Data were available for all 37 cases at 6 and 12 months and for 34 cases at 18 months. Demographics and disease characteristics were similar between groups. All 34 cases demonstrated clinical remission at 18 months (100% vs. 88%, P=0.114). Univariate and multivariate analyses did not show statistical significance. Dose intensification was seen more often in the cases at 18 months., Conclusion: All of our moderate-to-severe pediatric Crohn's disease patients who received prospective therapeutic drug monitoring of infliximab were in clinical remission at follow up, but this was not statistically significantly different from the 88% clinical remission rate of the control group., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Five patients with deep pelvic abscesses underwent computed tomography (CT)-guided catheter drainage using a transrectal approach. The use of an outer removable plastic sheath over the catheter to facilitate positioning and prevent inadvertent damage to the mucosal wall is described. This new approach using CT guidance is discussed and the alternative routes reviewed.

We have examined the immunosuppressive effects of combined azathioprine (Aza) and ciclosporin (CS) in two groups of mongrel dogs receiving kidney allografts. In group 1, Aza and CS were given together daily after transplantation and in group 2 twice the dose of each drug was given separately on alternate days. Doses were halved in each group at successive 84-day intervals and all immunosuppression was stopped on day 336. Thus the same total amounts of Aza and CS were given to all recipients in both groups. Up to day-60 the incidence of rejection in each group was similar, thereafter recipients in group 1 were more susceptible to fatal infection and marrow hypoplasia. This accounted for the difference in long-term survival between the two groups (1/14 in group 1, 5/12 in group 2 at day 420). Subsequently, two long-term survivors in group 2 died, 1 on day 452 from chronic rejection and the other on day 529 from gastroenteritis with a histologically normal allograft kidney. An in vitro analysis of the alloreactive repertoire of two healthy recipients in group 2, bearing each other's kidneys for more than 2.5 years and more than 500 days without immunosuppression, showed a profound donor-specific defect which could account for their operationally tolerant state.