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Abstract The promise of innovation in humanitarian contexts has generated an expanding literature, from academics as well as practitioners. However, the field has become characterised by conceptual ambiguity and insular approaches, inhibiting the integration of findings and best practices. Therefore, this paper aims to identify the key concepts, definitions, and themes in humanitarian innovation (HI) research by applying a systematic literature review and content analysis. Based on data from 301 publications, we analyse scholarly and practitioner articles addressing the topic of humanitarian innovation. Our analysis suggests that efforts to reform the humanitarian system by leveraging innovation have been primarily ad hoc, fragmented, and serving miscellaneous separate objectives. This results in the implementation of incremental improvements, rather than transformative change throughout the sector. To bridge the gap between the various conceptualisations of HI, we propose a conceptual framework that provides a system perspective on HI, which includes the institutions, actors, contextual factors, and outputs of the system. The implications of our finding for further research and policy are discussed as well. Points for practitioners • Ensure active participation and inclusion of affected populations in innovation agendas and processes. • Strengthen collaborative efforts among actors (donors, practitioners, private sector, intermediaries, NGOs) in humanitarian sector to increase coordination, knowledge exchange, and bundling of resources for innovation. • Facilitate evidence-based approaches and data-driven decision-making, for the operationalisation of appropriate innovations. • Increase the quality and quantity of funding going to innovation actors, and steer funding towards innovations explicitly catering to the needs of affected populations. Graphical Abstract

KeYmaeraX is a Hoare-style theorem prover for hybrid systems. A hybrid system can be seen as an aggregation of both discrete and continuous variables, whose values can change abruptly or continuously, respectively. KeYmaeraX supports only variables having the primitive type bool or real. Due to the mixture of discrete and continuous system elements, one promising application area for KeYmaeraX are closed-loop control systems. A closed-loop control system consists of a plant and a controller. While the plant is basically an aggregation of continuous variables whose values change over time accordingly to physical laws, the controller can be seen as an algorithm formulated in a classical programming language. In this paper, we review some recent extensions of the proof calculus applied by KeYmaeraX that make formal proofs on the stability of dynamic systems more feasible. Based on an example, we first introduce to the topic and prove asymptotic stability of a given system in a hand-written mathematical style. This approach is then compared with a formal encoding of the problem and a formal proof established in KeYmaeraX. We also discuss open problems such as the formalization of asymptotic stability.

During the climb flight of big passenger airplanes, the airplane’s vertical movement, i.e. its pitch angle, results from the elevator deflection angle chosen by the pilot. If the pitch angle becomes too large, the airplane is in danger of an airflow disruption at the wings, which can cause the airplane to crash. In some airplanes, the pilot is assisted by a software whose task is to prevent airflow disruptions. When the pitch angle becomes greater than a certain threshold, the software overrides the pilot’s decisions with respect to the elevator deflection angle and enforces presumably safe values. While the assistance software can help to prevent human failures, the software itself is also prone to errors and is - generally - a risk to be assessed carefully. For example, if software designers have forgotten that sensors might yield wrong data, the software might cause the pitch angle to become negative. Consequently, the airplane loses height and can - eventually - crash.In this paper, we provide an executable model written in Matlab/Simulink® for the control system of a passenger airplane. Our model takes also into account the software assisting the pilot to prevent airflow disruptions. When simulating the climb flight using our model, it is easy to see that the airplane might lose height in case the data provided by the pitch angle sensor are wrong. For the opposite case of correct sensor data, the simulation suggests that the control system works correctly and is able to prevent airflow disruptions effectively.The simulation, however, is not a guarantee for the control system to be safe. For this reason, we translate the Matlab/Simulink® -model into a hybrid program (HP), i.e. into the input syntax of the theorem prover KeYmaera. This paves the way to formally verify safety properties of control systems modelled in Matlab/Simulink®. As an additional contribution of this paper, we discuss the current limitations of our transformation. For example, it turns out that simple proportional (P) controllers can be easily represented by HP programs, but more advanced PD (proportional-derivative) or PID (proportional-integral-derivative) controllers can be represented as HP programs only in exceptional cases.

KeYmaera is an interactive theorem prover and is used to verify safety properties of cyber-physical systems (CPSs). It implements a Dynamic Logic for Hybrid Programs (HPs), while a HP models a CPS very precisely. Verifying properties of a given system in KeYmaera can become a challenge for a user since the proof is authored in a classical sequent calculus framework and a successful proof requires from the user intimate knowledge of the available calculus rules. Another barrier for widespread application of KeYmaera is the purely textual representation of current proof goals, what requires from the user very good training, experience, and patience. In this paper, we present an alternative verification approach based on KeYmaera, which drastically improves usability and minimizes user interaction. The main idea is to let the user annotate invariants and contracts to states of the hybrid automaton. Thus, the user can employ the graphical representation of the modelled system and is not bound to the purely textual form of hybrid programs as in KeYmaera. Based on the user-provided contracts, one can generate proof obligations, which are much simpler than the original proof goal in KeYmaera. The article is published in the authors’ wording.

Abstract. The notation of state machines is widely adopted as a formalism to describe the behaviour of systems. Usually, multiple state machine models can be developed for the very same software system. Some of these models might turn out to be equivalent, but, in many cases, different state machines describing the same system also differ in their level of abstraction. In this paper, we present an approach to actually measure the abstractness level of state machines w.r.t. a given implemented software system. A state machine is considered to be less abstract when it is conceptionally closer to the implemented system. In our approach, this distance between state machine and implementation is measured by applying coverage criteria known from software mutation testing. Abstractness of state machines can be considered as a new metric. As for other metrics as well, a known value for the abstractness of a given state machine allows to assess its quality in terms of a simple number. In model-based software development projects, the abstract metric can help to prevent model degradation since it can actually measure the semantic distance from the behavioural specification of a system in form of a state machine to the current implementation of the system. In contrast to other metrics for state machines, the abstractness cannot be statically computed based on the state machine’s structure, but requires to execute both state machine and corresponding system implementation. The article is published in the author’s wording.

Abstract Despite significant progress in the treatment of multiple myeloma (MM), relapsed/refractory patients urgently require more effective therapies. We here describe the discovery, mechanism of action, and preclinical anti‐MM activity of engineered toxin body MT‐0169, a next‐generation immunotoxin comprising a CD38‐specific antibody fragment linked to a de‐immunized Shiga‐like toxin A subunit (SLTA) payload. We show that specific binding of MT‐0169 to CD38 on MM cell lines triggers rapid internalization of SLTA, causing cell death via irreversible ribosome inhibition, protein synthesis blockade, and caspase 3/7 activation. In co‐culture experiments, bone marrow mesenchymal stromal cells did not induce drug resistance against MT‐0169. In the preclinical setting, MT‐0169 effectively lysed primary MM cells from newly diagnosed and heavily pretreated MM patients, including those refractory to daratumumab, with minimal toxicity against nonmalignant hematopoietic cells. MM cell lysis showed a significant correlation with their CD38 expression levels but not with cytogenetic risk, tumor load, or number of prior lines of therapy. Finally, MT‐0169 showed efficient in vivo anti‐MM activity in various mouse xenograft models, including one in which MM cells are grown in a humanized bone marrow‐like niche. These findings support clinical investigation of MT‐0169 in relapsed/refractory MM patients, including those refractory to CD38‐targeting immunotherapies.