Agent based simulation to optimise emergency departments

Nowadays, many of the health care systems are large and complex environments and quite dynamic, specifically Emergency Departments, EDs. It is opened and working 24 hours per day throughout the year with limited resources, whereas it is overcrowded. Thus, is mandatory to simulate EDs to improve qualitatively and quantitatively their performance. This improvement can be achieved modelling and simulating EDs using Agent-Based Model, ABM and optimising many different staff scenarios. This work optimises the staff configuration of an ED. In order to do optimisation, objective functions to minimise or maximise have to be set. One of those objective functions is to find the best or optimum staff configuration that minimise patient waiting time. The staff configuration comprises: doctors, triage nurses, and admissions, the amount and sort of them. Staff configuration is a combinatorial problem, that can take a lot of time to be solved. HPC is used to run the experiments, and encouraging results were obtained. However, even with the basic ED used in this work the search space is very large, thus, when the problem size increases, it is going to need more resources of processing in order to obtain results in an acceptable time.

Experimental calcium oxalate crystal production and dissolution by selected wood rot fungi.

Twenty-six species of white-rotting Agaricomycotina fungi (Basidiomycota) were screened for their ability to produce calcium-oxalate (CaOx) crystals in vitro. Most were able to produce CaOx crystals in malt agar medium in the absence of additional calcium. In the same medium enriched with Ca2+, all the species produced CaOx crystals (weddellite or whewellite). Hyphae of four species (Ganoderma lucidum, Polyporus ciliatus, Pycnoporus cinnabarinus, and Trametes versicolor) were found coated with crystals (weddellite/whewellite). The production of CaOx crystals during the growth phase was confirmed by an investigation of the production kinetics for six of the species considered in the initial screening (Pleurotus citrinopileatus, Pleurotus eryngii, Pleurotus ostreatus, P. cinnabarinus, Trametes suaveolens, and T. versicolor). However, the crystals produced during the growth phase disappeared from the medium over time in four of the six species (P. citrinopileatus, P. eryngii, P. cinnabarinus, and T. suaveolens). For P. cinnabarinus, the disappearance of the crystals was correlated with a decrease in the total oxalate concentration measured in the medium from 0.65 μg mm−2 (at the maximum accumulation rate) to 0.30 μg mm−2. The decrease in the CaOx concentration was correlated with a change in mycelia morphology. The oxalate dissolution capability of all the species was also tested in a medium containing calcium oxalate as the sole source of carbon (modified Schlegel medium). Three species (Agaricus blazei, Pleurotus tuberregium, and P. ciliatus) presented a dissolution halo around the growth zone. This study shows that CaOx crystal production is a widespread phenomenon in white-rot fungi, and that an excess of Ca2+ can enhance CaOx crystal production. In addition, it shows that some white-rot fungal species are capable of dissolving CaOx crystals after growth has ceased. These results highlight a diversity of responses around the production or dissolution of calcium oxalate in white-rot fungi and reveal an unexpected potential importance of fungi on the oxalate cycle in the environment.

Artificial Snow Optimization in Winter Sport Destinations Using a Multi-agent Simulation

This paper presents the Juste-Neige system for predicting the snow height on the ski runs of a resort using a multi-agent simulation software. Its aim is to facilitate snow cover management in order to i) reduce the production cost of artificial snow and to improve the profit margin for the companies managing the ski resorts; and ii) to reduce the water and energy consumption, and thus to reduce the environmental impact, by producing only the snow needed for a good skiing experience. The software provides maps with the predicted snow heights for up to 13 days. On these maps, the areas most exposed to snow erosion are highlighted. The software proceeds in three steps: i) interpolation of snow height measurements with a neural network; ii) local meteorological forecasts for every ski resort; iii) simulation of the impact caused by skiers using a multi-agent system. The software has been evaluated in the Swiss ski resort of Verbier and provides useful predictions.

Acute antihypertensive effect of angiotensin converting enzyme inhibition and calcium entry blockade.

The acute blood pressure response to an angiotensin converting enzyme inhibitor (enalaprilat) was compared in patients with uncomplicated essential hypertension with that obtained under similar conditions with a calcium entry blocker (nifedipine). The patients were studied after a 3 week washout period. At a 48 h interval, each patient received in randomized order either enalaprilat (5 mg i.v.) or nifedipine (10 mg p.o.). Enalaprilat and nifedipine were equally effective in acutely lowering blood pressure. However, good responders to one agent were not necessarily good responders to the other.

Increase of a Calcium Independent Transglutaminase Activity in the Erythrocyte during the Infection with Plasmodium falciparum

We have studied the activity of a calcium dependent transglutaminase (EC 2.3.2.13) during the growth of the parasite Plasmodium falciparum inside the infected human erythrocyte. There is only one detectable transglutaminase in the two-cell-system, and its origin is erythrocytic. No activity was detected in preparations of the parasite devoid of erythrocyte cytoplasm. The Michaelis Menten constants (Km) of the enzyme for the substrates N'N'dimethylcaseine and putrescine were undistinguishable whether the cell extracts used in their determination were obtained from normal or from infected red cells. The total activity of transglutaminase in stringently synchronized cultures, measured at 0.5mM Ca2+, decreased with the maturation of the parasite. However, a fraction which became irreversibly activated and independent of calcium concentration was detected. The proportion of this fraction grew with maturation; it represented only 20% of the activity in 20 hr-old-trophozoites while in 48-hr-schizonts it was more than 85% of the total activity. The activation of this fraction of transglutaminase did not depend on an increase in the erythrocyte cytoplasmic calcium, since most of the calcium was shown to be located in the parasite.

The fou2 mutation in the major vacuolar cation channel TPC1 confers tolerance to inhibitory luminal calcium.

The SV channel encoded by the TPC1 gene represents a Ca(2+)- and voltage-dependent vacuolar cation channel. Point mutation D454N within TPC1, named fou2 for fatty acid oxygenation upregulated 2, results in increased synthesis of the stress hormone jasmonate. As wounding causes Ca2+ signals and cytosolic Ca2+ is required for SV channel function, we here studied the Ca(2+)-dependent properties of this major vacuolar cation channel with Arabidopsis thaliana mesophyll vacuoles. In patch clamp measurements, wild-type and fou2 SV channels did not exhibit differences in cytosolic Ca2+ sensitivity and Ca2+ impermeability. K+ fluxes through wild-type TPC1 were reduced or even completely faded away when vacuolar Ca2+ reached the 0.1-mm level. The fou2 protein under these conditions, however, remained active. Thus, D454N seems to be part of a luminal Ca2+ recognition site. Thereby the SV channel mutant gains tolerance towards elevated luminal Ca2+. A three-fold higher vacuolar Ca/K ratio in the fou2 mutant relative to wild-type plants seems to indicate that fou2 can accumulate higher levels of vacuolar Ca(2+) before SV channel activity vanishes and K(+) homeostasis is impaired. In response to wounding fou2 plants might thus elicit strong vacuole-derived cytosolic Ca2+ signals resulting in overproduction of jasmonate.

Renal protection with calcium antagonists: the role of lercanidipine.

Abstract Background: Clinical research in the field of hypertension is now increasingly focusing on the potential effects of antihypertensive treatments that may go beyond the reduction of blood pressure (BP). In particular, renal protection appears as a desirable goal, especially considering that hypertension is associated with an increased risk of developing kidney damage, which may eventually lead to end-stage renal disease and a higher mortality. Dihydropyridine calcium channel blockers (CCBs) are widely used in the field of hypertension therapy but the different renal effects of the various CCBs have been poorly explored to date. Scope: This review will discuss available evidence on the renal effects of two calcium channel blockers: amlodipine and lercanidipine, on the basis of clinical data. Methods: MEDLINE and EMBASE were searched for inclusion of relevant studies. No limitations in time were considered. Results: Results from preclinical and clinical studies suggest that amlodipine is overall less effective in terms of renal protection when compared with other antihypertensive tested agents. Its beneficial effect in retarding the progression of renal disease is achievable only when combined with a blocker of the renin-angiotensin system. Conversely lercanidipine seems to provide renal protection in a similar way to ACE inhibitors, probably thanks to its mechanism of action which acts directly on the afferent and efferent renal arterioles. Conclusions: Treatment of hypertension with CCBs should take into consideration the special effects of each single agent at different levels; lercanidipine for example may play a useful role in the management not only of hypertension but also in renal protection of hypertensive patients.

Simulation des caractéristiques ECG du syndrome de Brugada à l'aide d'un programme de modélisation 3D

Introduction : Le syndrome de Brugada, décrit en 1992 par Pedro et Josep Brugada, est un syndrome cardiaque caractérisé par un sus-décalage particulier du segment ST associé à un bloc de branche droit atypique au niveau des dérivations ECG V1 à V3. Les altérations ECG du syndrome de Brugada sont classifiées en 3 types dont seul le type 1 est diagnostique. Les mécanismes physiopathologiques exacts de ce syndrome sont pour le moment encore controversés. Plusieurs hypothèses sont proposées dans la littérature dont deux principales retiennent l'attention : 1) le modèle du trouble de repolarisation stipule des potentiels d'action réduits en durée et en amplitude liés à un changement de répartition de canaux potassiques 2) le modèle du trouble de dépolarisation spécifie un retard de conduction se traduisant par une dépolarisation retardée. Dans le STEMI, un sus-décalage ST ressemblant à celui du syndrome de Brugada est expliqué par deux théories : 1) le courant de lésion diastolique suggère une élévation du potentiel diastolique transformé artificiellement en sus-décalage ST par les filtres utilisés dans tous les appareils ECG.¦Objectif : Recréer les manifestations ECG du syndrome de Brugada en appliquant les modifications du potentiel d'action des cardiomyocytes rapportées dans la littérature.¦Méthode : Pour ce travail, nous avons utilisé "ECGsim", un simulateur informatique réaliste d'ECG disponible gratuitement sur www.ecgsim.org. Ce programme est basé sur une reconstruction de l'ECG de surface à l'aide de 1500 noeuds représentant chacun les potentiels d'action des ventricules droit et gauche, épicardiques et endocardiques. L'ECG simulé peut être donc vu comme l'intégration de l'ensemble de ces potentiels d'action en tenant compte des propriétés de conductivité des tissus s'interposant entre les électrodes de surface et le coeur. Dans ce programme, nous avons définit trois zones, de taille différente, comprenant la chambre de chasse du ventricule droit. Pour chaque zone, nous avons reproduit les modifications des potentiels d'action citées dans les modèles du trouble de repolarisation et de dépolarisation et des théories de courant de lésion systolique et diastolique. Nous avons utilisé, en plus des douze dérivations habituelles, une électrode positionnée en V2IC3 (i.e. 3ème espace intercostal) sur le thorax virtuel du programme ECGsim.¦Résultats : Pour des raisons techniques, le modèle du trouble de repolarisation n'a pas pu être entièrement réalisée dans ce travail. Le modèle du trouble de dépolarisation ne reproduit pas d'altération de type Brugada mais un bloc de branche droit plus ou moins complet. Le courant de lésion diastolique permet d'obtenir un sus-décalage ST en augmentant le potentiel diastolique épicardique des cardiomyocytes de la chambre de chasse du ventricule droit. Une inversion de l'onde T apparaît lorsque la durée du potentiel d'action est prolongée. L'amplitude du sus-décalage ST dépend de la valeur du potentiel diastolique, de la taille de la lésion et de sa localisation épicardique ou transmurale. Le courant de lésion systolique n'entraîne pas de sus-décalage ST mais accentue l'amplitude de l'onde T.¦Discussion et conclusion : Dans ce travail, l'élévation du potentiel diastolique avec un prolongement de la durée du potentiel d'action est la combinaison qui reproduit le mieux les altérations ECG du Brugada. Une persistance de cellules de type nodal au niveau de la chambre de chasse du ventricule droit pourrait être une explication à ces modifications particulières du potentiel d'action. Le risque d'arythmie dans la Brugada pourrait également être expliqué par une automaticité anormale des cellules de type nodal. Ainsi, des altérations des mécanismes cellulaires impliqués dans le maintien du potentiel diastolique pourraient être présentes dans le syndrome de Brugada, ce qui, à notre connaissance, n'a jamais été rapporté dans la littérature.

Dynamic simulation of regulatory networks using SQUAD.

BACKGROUND: The ambition of most molecular biologists is the understanding of the intricate network of molecular interactions that control biological systems. As scientists uncover the components and the connectivity of these networks, it becomes possible to study their dynamical behavior as a whole and discover what is the specific role of each of their components. Since the behavior of a network is by no means intuitive, it becomes necessary to use computational models to understand its behavior and to be able to make predictions about it. Unfortunately, most current computational models describe small networks due to the scarcity of kinetic data available. To overcome this problem, we previously published a methodology to convert a signaling network into a dynamical system, even in the total absence of kinetic information. In this paper we present a software implementation of such methodology. RESULTS: We developed SQUAD, a software for the dynamic simulation of signaling networks using the standardized qualitative dynamical systems approach. SQUAD converts the network into a discrete dynamical system, and it uses a binary decision diagram algorithm to identify all the steady states of the system. Then, the software creates a continuous dynamical system and localizes its steady states which are located near the steady states of the discrete system. The software permits to make simulations on the continuous system, allowing for the modification of several parameters. Importantly, SQUAD includes a framework for perturbing networks in a manner similar to what is performed in experimental laboratory protocols, for example by activating receptors or knocking out molecular components. Using this software we have been able to successfully reproduce the behavior of the regulatory network implicated in T-helper cell differentiation. CONCLUSION: The simulation of regulatory networks aims at predicting the behavior of a whole system when subject to stimuli, such as drugs, or determine the role of specific components within the network. The predictions can then be used to interpret and/or drive laboratory experiments. SQUAD provides a user-friendly graphical interface, accessible to both computational and experimental biologists for the fast qualitative simulation of large regulatory networks for which kinetic data is not necessarily available.