BACKGROUND: We aimed to examine clinical features, and outcomes of consecutive molecularly characterized patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy. METHODS: A retrospective, longitudinal multicenter cohort of consecutive children and adults with a genetic diagnosis of Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy between 2002 and 2019 was assembled. We defined a priori 3 different patterns of left ventricular remodeling during follow-up: (1) an increase in ≥15% of the maximal left ventricular wall thickness (MLVWT), both in mm and z -score (progression); (2) a reduction ≥15% of the MLVWT, both in mm and z -score (absolute regression); (3) a reduction ≥15% of the MLVWT z -score with a stable MLVWT in mm (relative regression). The primary study end point was a composite of cardiovascular death, heart transplantation, and appropriate implantable cardioverter defibrillator-shock. RESULTS: The cohort comprised 42 patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy, with a median age at diagnosis of 3.5 (interquartile range, 0.2–12.3) years. Freedom from primary end point was 92.7% (95% CI, 84.7%–100%) 1 year after presentation and 80.9% (95% CI, 70.1%–90.7%) at 5 years. Patients with MLVWT z -score >13.7 showed reduced survival compared with those with <13.7. During a median follow-up of 3.7 years (interquartile range, 2.6–7.9), absolute regression was the most common type of left ventricular remodeling (n=9, 31%), followed by progression (n=6, 21%), and relative regression (n=6, 21%). CONCLUSIONS: These findings provide insights into the natural history of left ventricular hypertrophy, and can help inform clinicians regarding risk stratification and clinical outcomes in patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy.

One important paradigm proposed in literature by the scientific community that advocates the viable system approach is the structure-system dichotomy for the capability to simplify the investigation of a phenomenon and recognize its scope and implications. The purpose of this paper is to provide a contribution to the debate which concerns the structure-system approach introducing the concept of interaction type as a bridge linking the relationship concept to that of interaction. The interaction type is first introduced in its simplest form using an UML class diagram that points out its role when the observer views changes from structure to system and from system to structure. Then, the recursive nature of interaction types is discussed in order to show how complex relationships, that involve more parties at several interaction levels, can be better represented and used. Finally, a model for the representation of transactions is proposed in which a transaction type can be interpreted as a particular case of interaction type and a transaction as an ordered set of interactions. Two case studies are presented in the paper; the first concerns an example of fund transfer and highlights how the interaction type hierarchy can be applied. The second case study is from the port community system of South Italy and shows how a clearance to enter or leave national waters can be described as "departure from" and "arrival to" interaction types.

The problem of performance evaluation of business processes supported by Workflow Management Systems is a recent research issue. In this paper we propose a measurement framework in which several aspects concerning the timing and working of a business process, either as a whole or in terms of its components, can be precisely quantified. Our approach is based on the workflow model introduced by the Workflow Management Coalition and introduces some fundamental measures from which a number of derived measures can be hierarchically obtained. The paper describes the basic structures and the primitive operators of the framework as well as the fundamental and derived measures. Techniques for the evaluation of complex processes are also discussed. The proposed framework is quite general and can be applied to research and commercial workflow management systems with relatively little implementation effort.

One important paradigm proposed in literature by the scientific community that advocates the viable system approach is the structure-system dichotomy for the capability to simplify the investigation of a phenomenon and recognize its scope and implications. The purpose of this paper is to provide a contribution to the debate which concerns the structure-system approach introducing the concept of interaction type as a bridge linking the relationship concept to that of interaction. The interaction type is first introduced in its simplest form using an UML class diagram that points out its role when the observer views changes from structure to system and from system to structure. Then, the recursive nature of interaction types is discussed in order to show how complex relationships, that involve more parties at several interaction levels, can be better represented and used. Finally, a model for the representation of transactions is proposed in which a transaction type can be interpreted as a particular case of interaction type and a transaction as an ordered set of interactions. Two case studies are presented in the paper; the first concerns an example of fund transfer and highlights how the interaction type hierarchy can be applied. The second case study is from the port community system of South Italy and shows how a clearance to enter or leave national waters can be described as "departure from" and "arrival to" interaction types.

Risk management in several application domains is receiving increasing attention in the last years especially when the risk management must be pursued in a network made of interacting systems. The motivation is that although risk management models and techniques are mature enough to handle risk in the context of a single system, risk evaluation in the setting of a network of systems is much more difficult to model and manage. Because of the lack of awareness of risk, it is difficult to perceive risks propagation within the network of systems. On the other hand, the lack of shared goals and knowledge represents itself a risk, so that we need a good paradigm to organize and communicate information.\ud \ud In this paper we first introduce a metamodel able to represent the fundamental structure from which distributed risk management models can be derived with respect to several application domains. This abstraction arises from an approach to risk management based on the definition of risk ontologies. A risk ontology is specialized to represent and share risk knowledge in a given application domain; changing the underlying ontology, the metamodel can be adapted to a new application domain so that the logic for risk management can be reused with a reasonable tailoring effort.\ud \ud Two case studies are discussed in the paper as possible implementation of risk management systems based on the proposed metamodel