Immune profiles in acute myeloid leukemia bone marrow associate with patient age, T-cell receptor clonality, and survival

The immunologic microenvironment in various solid tumors is aberrant and correlates with clinical survival. Here, we present a comprehensive analysis of the immune environment of acute myeloid leukemia (AML) bone marrow (BM) at diagnosis. We compared the immunologic landscape of formalin-fixed paraffin-embedded BM trephine samples from AML (n = 69), chronic myeloid leukemia (CML; n = 56), and B-cell acute lymphoblastic leukemia (B-ALL) patients (n 5 52) at diagnosis to controls (n = 12) with 30 immunophenotype markers using multiplex immunohistochemistry and computerized image analysis. We identified distinct immunologic profiles specific for leukemia subtypes and controls enabling accurate classification of AML (area under the curve [AUC] = 1.0), CML (AUC = 0.99), B-ALL (AUC = 0.96), and control subjects (AUC = 1.0). Interestingly, 2 major immunologic AML clusters differing in age, T-cell receptor clonality, and survival were discovered. A low proportion of regulatory T cells and pSTAT(+)cMAF(-) monocytes were identified as novel biomarkers of superior event-free survival in intensively treated AML patients. Moreover, we demonstrated that AML BM and peripheral blood samples are dissimilar in terms of immune cell phenotypes. To conclude, our study shows that the immunologic landscape considerably varies by leukemia subtype suggesting disease-specific immunoregulation. Furthermore, the association of the AML immune microenvironment with clinical parameters suggests a rationale for including immunologic parameters to improve disease classification or even patient risk stratification.Peer reviewe

Adding Priority to Event Structures

Event Structures (ESs) are mainly concerned with the representation of causal relationships between events, usually accompanied by other event relations capturing conflicts and disabling. Among the most prominent variants of ESs are Prime ESs, Bundle ESs, Stable ESs, and Dual ESs, which differ in their causality models and event relations. Yet, some application domains require further kinds of relations between events. Here, we add the possibility to express priority relationships among events. We exemplify our approach on Prime, Bundle, Extended Bundle, and Dual ESs. Technically, we enhance these variants in the same way. For each variant, we then study the interference between priority and the other event relations. From this, we extract the redundant priority pairs-notably differing for the types of ESs-that enable us to provide a comparison between the extensions. We also exhibit that priority considerably complicates the definition of partial orders in ESs.Comment: In Proceedings EXPRESS/SOS 2013, arXiv:1307.690

Semantic Embedding of Petri Nets into Event-B

We present an embedding of Petri nets into B abstract systems. The embedding is achieved by translating both the static structure (modelling aspect) and the evolution semantics of Petri nets. The static structure of a Petri-net is captured within a B abstract system through a graph structure. This abstract system is then included in another abstract system which captures the evolution semantics of Petri-nets. The evolution semantics results in some B events depending on the chosen policies: basic nets or high level Petri nets. The current embedding enables one to use conjointly Petri nets and Event-B in the same system development, but at different steps and for various analysis.Comment: 16 pages, 3 figure

Event structures for Petri nets with persistence

Event structures are a well-accepted model of concurrency. In a seminal paper by Nielsen, Plotkin and Winskel, they are used to establish a bridge between the theory of domains and the approach to concurrency proposed by Petri. A basic role is played by an unfolding construction that maps (safe) Petri nets into a subclass of event structures, called prime event structures, where each event has a uniquely determined set of causes. Prime event structures, in turn, can be identified with their domain of configurations. At a categorical level, this is nicely formalised by Winskel as a chain of coreflections. Contrary to prime event structures, general event structures allow for the presence of disjunctive causes, i.e., events can be enabled by distinct minimal sets of events. In this paper, we extend the connection between Petri nets and event structures in order to include disjunctive causes. In particular, we show that, at the level of nets, disjunctive causes are well accounted for by persistent places. These are places where tokens, once generated, can be used several times without being consumed and where multiple tokens are interpreted collectively, i.e., their histories are inessential. Generalising the work on ordinary nets, Petri nets with persistence are related to a new subclass of general event structures, called locally connected, by means of a chain of coreflections relying on an unfolding construction

The Metaphysics of Free Will: A Critique of Free Won’t as Double Prevention

The problem of free will is deeply linked with the causal relevance of mental events. The causal exclusion argument claims that, in order to be causally relevant, mental events must be identical to physical events. However, Gibb has recently criticized it, suggesting that mental events are causally relevant as double preventers. For Gibb, mental events enable physical effects to take place by preventing other mental events from preventing a behaviour to take place. The role of mental double preventers is hence similar to what Libet names free won’t, namely the ability to veto an action initiated unconsciously by the brain. In this paper I will propose an argument against Gibb’s account, the causal irrelevance argument, showing that Gibb’s proposal does not overcome the objection of systematic overdetermination of causal relevance, because mental double preventers systematically overdetermine physical double preventers, and therefore mental events are causally irrelevant

Fostering the social utility of events: an integrative framework for the strategic use of events in community development

Although the use of planned events for achieving community development has received academic attention from different disciplines, the findings of these literatures are not systematically used towards developing a common understanding aimed at fostering their social utility. The challenge then is to study from an integrated interdisciplinary perspective how the social value of events can be fostered and leveraged for community development. In addressing this challenge, the purpose of this conceptual paper is to shed light on the multi-layered processes that foster the social utility of events. To this end, the theoretical tenets of social leverage, event dramaturgy and social capital are employed and integrated. On this basis, a conceptual framework linking event processes and outcomes is proposed aimed to guide future interdisciplinary research towards strategically incorporating events in community development. This line of research can eventually help create synergies between different event genres and implement joint social leveraging strategies, hence, fostering and magnifying their overall social utility for host communities

Making space for proactive adaptation of rapidly changing coasts: a windows of opportunity approach

Coastlines are very often places where the impacts of global change are felt most keenly, and they are also often sites of high values and intense use for industry, human habitation, nature conservation and recreation. In many countries, coastlines are a key contested territory for planning for climate change, and also locations where development and conservation conflicts play out. As a “test bed” for climate change adaptation, coastal regions provide valuable, but highly diverse experiences and lessons. This paper sets out to explore the lessons of coastal planning and development for the implementation of proactive adaptation, and the possibility to move from adaptation visions to actual adaptation governance and planning. Using qualitative analysis of interviews and workshops, we first examine what the barriers are to proactive adaptation at the coast, and how current policy and practice frames are leading to avoidable lock-ins and other maladaptive decisions that are narrowing our adaptation options. Using examples from UK, we then identify adaptation windows that can be opened, reframed or transformed to set the course for proactive adaptation which links high level top-down legislative requirements with local bottom-up actions. We explore how these windows can be harnessed so that space for proactive adaptation increases and maladaptive decisions are reduced