Reducing Boolean networks with backward equivalence.

BACKGROUND: Boolean Networks (BNs) are a popular dynamical model in biology where the state of each component is represented by a variable taking binary values that express, for instance, activation/deactivation or high/low concentrations. Unfortunately, these models suffer from the state space explosion, i.e., there are exponentially many states in the number of BN variables, which hampers their analysis. RESULTS: We present Boolean Backward Equivalence (BBE), a novel reduction technique for BNs which collapses system variables that, if initialized with same value, maintain matching values in all states. A large-scale validation on 86 models from two online model repositories reveals that BBE is effective, since it is able to reduce more than 90% of the models. Furthermore, on such models we also show that BBE brings notable analysis speed-ups, both in terms of state space generation and steady-state analysis. In several cases, BBE allowed the analysis of models that were originally intractable due to the complexity. On two selected case studies, we show how one can tune the reduction power of BBE using model-specific information to preserve all dynamics of interest, and selectively exclude behavior that does not have biological relevance. CONCLUSIONS: BBE complements existing reduction methods, preserving properties that other reduction methods fail to reproduce, and vice versa. BBE drops all and only the dynamics, including attractors, originating from states where BBE-equivalent variables have been initialized with different activation values The remaining part of the dynamics is preserved exactly, including the length of the preserved attractors, and their reachability from given initial conditions, without adding any spurious behaviours. Given that BBE is a model-to-model reduction technique, it can be combined with further reduction methods for BNs.

MRGPRX2-mediated mast cell response to drugs used in perioperative procedures and anaesthesia.

The study of anaphylactoid reactions during perioperative procedures and anaesthesia represents a diagnostic challenge for allergists, as many drugs are administered simultaneously, and approximately half of them trigger allergic reactions without a verifiable IgE-mediated mechanism. Recently, mast cell receptor MRGPRX2 has been identified as a cause of pseudo-allergic drug reactions. In this study, we analyse the ability of certain drugs used during perioperative procedures and anaesthesia to induce MRGPRX2-dependent degranulation in human mast cells and sera from patients who experienced an anaphylactoid reaction during the perioperative procedure. Using a ß-hexosaminidase release assay, several drugs were seen to cause mast cell degranulation in vitro in comparison with unstimulated cells, but only morphine, vancomycin and cisatracurium specifically triggered this receptor, as assessed by the release of ß-hexosaminidase in the control versus the MRGPRX2-silenced cells. The same outcome was seen when measuring degranulation based on the percentage of CD63 expression at identical doses. Unlike that of the healthy controls, the sera of patients who had experienced an anaphylactoid reaction induced mast-cell degranulation. The degranulation ability of these sera decreased when MRGPRX2 was silenced. In conclusion, MRGPRX2 is a candidate for consideration in non-IgE-mediated allergic reactions to some perioperative drugs, reinforcing its role in mast cell responses and their pathophysiology.

Improvement of the Elevated Tryptase Criterion to Discriminate IgE- From Non-IgE-Mediated Allergic Reactions.

BACKGROUND: Differentiating between immunoglobulin E (IgE)-dependent and IgE-independent hypersensitivity reactions may improve the etiologic orientation and clinical management of patients with allergic reactions in the anesthesia setting. Serum tryptase levels may be useful to discriminate the immune mechanism of allergic reactions, but the diagnostic accuracy and optimal cutpoint remain unclear.We aimed to compare the diagnostic accuracy of tryptase during reaction (TDR) alone and the TDR/basal tryptase (TDR/BT) ratio for discriminating IgE- from non-IgE-mediated allergic reactions, and to estimate the best cut point for these indicators. METHODS: We included 111 patients (45% men; aged 3-99 years) who had experienced an allergic reaction, even though the allergic reaction could be nonanaphylactic. Allergy tests were performed to classify the reaction as an IgE- or non-IgE-mediated one. The area under the curve (AUC) of the receiver operating characteristic analysis was performed to estimate the discriminative ability of TDR and TDR/BT ratio. RESULTS: An IgE-mediated reaction was diagnosed in 49.5% of patients, and 56% of patients met anaphylaxis criteria. The median (quartiles) TDR for the IgE-mediated reactions was 8.0 (4.9-19.6) and 5.1 (3.5-8.1) for the non-IgE-mediated (P = .022). The median (quartiles) TDR/BT ratio was 2.7 (1.7-4.5) in IgE-mediated and 1.1 (1.0-1.6) in non-IgE-mediated reactions (P < .001). The TDR/BT ratio showed the greatest ability to discriminate IgE- from non-IgE-mediated reactions compared to TDR (AUC TDR/BT = 0.79 [95% confidence interval (CI), 0.70-0.88] and AUC TDR = 0.66 [95% CI, 0.56-0.76]; P = .001). The optimal cut point for TDR/BT (maximization of the sum of the sensitivity and specificity) was 1.66 (95% CI, 1.1-2.2). CONCLUSIONS: The TDR/BT ratio showed a significantly better discriminative ability than TDR to discriminate IgE- from non-IgE-mediated allergic reactions. An optimal TDR/BT ratio threshold of approximately 1.66 may be useful in clinical practice to classify allergic reactions as IgE- or non-IgE-mediated.

Routing in Mobile Wireless Sensor Networks: A Leader-Based Approach.

This paper presents a leader-based approach to routing in Mobile Wireless Sensor Networks (MWSN). Using local information from neighbour nodes, a leader election mechanism maintains a spanning tree in order to provide the necessary adaptations for efficient routing upon the connectivity changes resulting from the mobility of sensors or sink nodes. We present two protocols following the leader election approach, which have been implemented using Castalia and OMNeT++. The protocols have been evaluated, besides other reference MWSN routing protocols, to analyse the impact of network size and node velocity on performance, which has demonstrated the validity of our approach.

The incidence of perioperative hypersensitivity reactions: a single-center, prospective, cohort study.

BACKGROUND: The incidence of perioperative hypersensitivity reactions, which can be life-threatening, ranges from 1 in 20,000 to 1 in 1361. These reactions are usually classified as IgE or non-IgE mediated. The aim of this study was to determine the incidence of allergic reactions during general anesthesia in our hospital, to establish the incidence of the allergic reactions for each drug used, to assess the frequency of IgE-mediated reactions in even mild reactions, and to compare the degree of agreement between anesthesiologist suspicion and allergy diagnosis. METHODS: We included patients diagnosed with a clinical hypersensitivity reaction during a procedure under general anesthesia over a 30-month period (February 2008 to August 2010). Plasma histamine and serum tryptase concentrations were determined in these patients. We performed skin tests to diagnose the causative agent. Data from the hospital electronic prescribing system were collected to determine the ratio of reactions for each drug. RESULTS: During the study period, 16,946 anesthetic procedures were performed (53% involved males; mean age, 51.6 years). Forty-four perianesthetic reactions were recorded, and the ratio of reactions was 1 in 385 operations (95% confidence interval, 1/529-1/287). Twenty-five reactions (25/44; 57%) occurred during the induction of anesthesia. Twenty-one reactions (21/44; 48%) were mild, involving only skin, and 23 of 44 (52%) were anaphylactic reactions. Four of 10 patients who had only a rash experienced IgE-mediated reactions. Five surgeries (11%) were suspended because of the severity of the reactions. Fifteen reactions (15/30; 50%) were IgE mediated, and, in 2 of 30 (7%), a non-IgE agent was found (cold urticaria and nonsteroidal anti-inflammatory drug intolerance). The ratio of reactions for each drug was as follows: protamine, 1 in 468; cisatracurium, 1 in 1388; amoxicillin-clavulanate, 1 in 1968; atracurium, 1 in 2039; and dipyrone, 1 in 3159. CONCLUSIONS: Perioperative reactions are more common than previously reported. Mild hypersensitivity perioperative reactions-involving only skin-should be considered in evaluating patients because a substantial number of these reactions are IgE mediated.

Urban waste recycling behavior: antecedents of participation in a selective collection program.

The aim of this study is to analyze the antecedents of urban waste recycling behavior. To achieve this goal, a concrete urban waste management program was chosen. The study focuses on the Selective Collection Program (SCP) in Zaragoza, a medium-sized city in northeastern Spain. The research starts with a conceptual model in which the variables that potentially affect recycling behavior can be classified into two groups: incentives and barriers. Moreover, the sociodemographic characteristics of the individuals are included in our study. Given that the proposed model requires specification of latent variables or constructs, the analysis is based on the Structural Equation Models (SEM) methodology. The results revealed that environmental awareness, knowledge of the environmental impact of urban waste, and the positive perception of management by local government exercise a positive effect on individual recycling behavior, while perceived personal difficulties (space and time availability) and distance to and from the container have a negative effect. As regards sociodemographic variables, this study found that annual family income sustains a negative relationship with recycling behavior, while age maintains a positive one. The results obtained clearly show the important role that the public authorities play, especially municipal governments, in achieving the waste recycling objectives established in accordance with international legislation.