An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase.

In order to identify new compounds to treat Chagas disease during the acute phase with higher activity and lower toxicity than the reference drug benznidazole (Bz), two hydroxyphthalazine derivative compounds were prepared and their trypanocidal effects against Trypanosoma cruzi were evaluated by light microscopy through the determination of IC50 values. Cytotoxicity was determined by flow cytometry assays against Vero cells. In vivo assays were performed in BALB/c mice, in which the parasitemia levels were quantified by fresh blood examination; the assignment of a cure was determined by reactivation of blood parasitemia levels after immunosuppression. The mechanism of action was elucidated at metabolic and ultra-structural levels, by (1)H NMR and TEM studies. Finally, as these compounds are potentially capable of causing oxidative damage in the parasites, the study was completed, by assessing their activity as potential iron superoxide dismutase (Fe-SOD) inhibitors. High-selectivity indices observed in vitro were the basis of promoting one of the tested compounds to in vivo assays. The tests on the murine model for the acute phase of Chagas disease showed better parasitemia inhibition values than those found for Bz. Compound 2 induced a remarkable decrease in the reactivation of parasitemia after immunosuppression. Compound 2 turned out to be a great inhibitor of Fe-SOD. The high antiparasitic activity and low toxicity together with the modest costs for the starting materials render this compound an appropriate molecule for the development of an affordable anti-Chagas agent.

Flow-R, a model for susceptibility mapping of debris flows and other gravitational hazards at a regional scale

The development of susceptibility maps for debris flows is of primary importance due to population pressure in hazardous zones. However, hazard assessment by processbased modelling at a regional scale is difficult due to the complex nature of the phenomenon, the variability of local controlling factors, and the uncertainty in modelling parameters. A regional assessment must consider a simplified approach that is not highly parameter dependant and that can provide zonation with minimum data requirements. A distributed empirical model has thus been developed for regional susceptibility assessments using essentially a digital elevation model (DEM). The model is called Flow-R for Flow path assessment of gravitational hazards at a Regional scale (available free of charge under www.flow-r.org) and has been successfully applied to different case studies in various countries with variable data quality. It provides a substantial basis for a preliminary susceptibility assessment at a regional scale. The model was also found relevant to assess other natural hazards such as rockfall, snow avalanches and floods. The model allows for automatic source area delineation, given user criteria, and for the assessment of the propagation extent based on various spreading algorithms and simple frictional laws.We developed a new spreading algorithm, an improved version of Holmgren's direction algorithm, that is less sensitive to small variations of the DEM and that is avoiding over-channelization, and so produces more realistic extents. The choices of the datasets and the algorithms are open to the user, which makes it compliant for various applications and dataset availability. Amongst the possible datasets, the DEM is the only one that is really needed for both the source area delineation and the propagation assessment; its quality is of major importance for the results accuracy. We consider a 10m DEM resolution as a good compromise between processing time and quality of results. However, valuable results have still been obtained on the basis of lower quality DEMs with 25m resolution.

Computational fluid dynamics of the right ventricular outflow tract and of the pulmonary artery: a bench model of flow dynamics.

OBJECTIVES: The reconstruction of the right ventricular outflow tract (RVOT) with valved conduits remains a challenge. The reoperation rate at 5 years can be as high as 25% and depends on age, type of conduit, conduit diameter and principal heart malformation. The aim of this study is to provide a bench model with computer fluid dynamics to analyse the haemodynamics of the RVOT, pulmonary artery, its bifurcation, and left and right pulmonary arteries that in the future may serve as a tool for analysis and prediction of outcome following RVOT reconstruction. METHODS: Pressure, flow and diameter at the RVOT, pulmonary artery, bifurcation of the pulmonary artery, and left and right pulmonary arteries were measured in five normal pigs with a mean weight of 24.6 ± 0.89 kg. Data obtained were used for a 3D computer fluid-dynamics simulation of flow conditions, focusing on the pressure, flow and shear stress profile of the pulmonary trunk to the level of the left and right pulmonary arteries. RESULTS: Three inlet steady flow profiles were obtained at 0.2, 0.29 and 0.36 m/s that correspond to the flow rates of 1.5, 2.0 and 2.5 l/min flow at the RVOT. The flow velocity profile was constant at the RVOT down to the bifurcation and decreased at the left and right pulmonary arteries. In all three inlet velocity profiles, low sheer stress and low-velocity areas were detected along the left wall of the pulmonary artery, at the pulmonary artery bifurcation and at the ostia of both pulmonary arteries. CONCLUSIONS: This computed fluid real-time model provides us with a realistic picture of fluid dynamics in the pulmonary tract area. Deep shear stress areas correspond to a turbulent flow profile that is a predictive factor for the development of vessel wall arteriosclerosis. We believe that this bench model may be a useful tool for further evaluation of RVOT pathology following surgical reconstructions.

Calibration of stochastic volatility models via second order approximation: the Heston model case

Using a suitable Hull and White type formula we develop a methodology to obtain asecond order approximation to the implied volatility for very short maturities. Using thisapproximation we accurately calibrate the full set of parameters of the Heston model. Oneof the reasons that makes our calibration for short maturities so accurate is that we alsotake into account the term-structure for large maturities. We may say that calibration isnot "memoryless", in the sense that the option's behavior far away from maturity doesinfluence calibration when the option gets close to expiration. Our results provide a wayto perform a quick calibration of a closed-form approximation to vanilla options that canthen be used to price exotic derivatives. The methodology is simple, accurate, fast, andit requires a minimal computational cost.

A new alternative method for testing skin irritation using a human skin model: a pilot study.

Studies assessing skin irritation to chemicals have traditionally used laboratory animals; however, such methods are questionable regarding their relevance for humans. New in vitro methods have been validated, such as the reconstructed human epidermis (RHE) model (Episkin®, Epiderm®). The comparison (accuracy) with in vivo results such as the 4-h human patch test (HPT) is 76% at best (Epiderm®). There is a need to develop an in vitro method that better simulates the anatomo-pathological changes encountered in vivo. To develop an in vitro method to determine skin irritation using human viable skin through histopathology, and compare the results of 4 tested substances to the main in vitro methods and in vivo animal method (Draize test). Human skin removed during surgery was dermatomed and mounted on an in vitro flow-through diffusion cell system. Ten chemicals with known non-irritant (heptylbutyrate, hexylsalicylate, butylmethacrylate, isoproturon, bentazon, DEHP and methylisothiazolinone (MI)) and irritant properties (folpet, 1-bromohexane and methylchloroisothiazolinone (MCI/MI)), a negative control (sodiumchloride) and a positive control (sodiumlaurylsulphate) were applied. The skin was exposed at least for 4h. Histopathology was performed to investigate irritation signs (spongiosis, necrosis, vacuolization). We obtained 100% accuracy with the HPT model; 75% with the RHE models and 50% with the Draize test for 4 tested substances. The coefficients of variation (CV) between our three test batches were <0.1, showing good reproducibility. Furthermore, we reported objectively histopathological irritation signs (irritation scale): strong (folpet), significant (1-bromohexane), slight (MCI/MI at 750/250ppm) and none (isoproturon, bentazon, DEHP and MI). This new in vitro test method presented effective results for the tested chemicals. It should be further validated using a greater number of substances; and tested in different laboratories in order to suitably evaluate reproducibility.

Effect of expiratory flow limitation on respiratory mechanical impedance: a model study

Large phasic variations of respiratory mechanical impedance (Zrs) have been observed during induced expiratory flow limitation (EFL) (M. Vassiliou, R. Peslin, C. Saunier, and C. Duvivier. Eur. Respir. J. 9: 779-786, 1996). To clarify the meaning of Zrs during EFL, we have measured from 5 to 30 Hz the input impedance (Zin) of mechanical analogues of the respiratory system, including flow-limiting elements (FLE) made of easily collapsible rubber tubing. The pressures upstream (Pus) and downstream (Pds) from the FLE were controlled and systematically varied. Maximal flow (Vmax) increased linearly with Pus, was close to the value predicted from wave-speed theory, and was obtained for Pus-Pds of 4-6 hPa. The real part of Zin started increasing abruptly with flow (V) >85%Vmax and either further increased or suddenly decreased in the vicinity of V¿max. The imaginary part of Zin decreased markedly and suddenly above 95%Vmax. Similar variations of Zin during EFL were seen with an analogue that mimicked the changes of airway transmural pressure during breathing. After pressure andV measurements upstream and downstream from the FLE were combined, the latter was analyzed in terms of a serial (Zs) and a shunt (Zp) compartment. Zs was consistent with a large resistance and inertance, and Zp with a mainly elastic element having an elastance close to that of the tube walls. We conclude that Zrs data during EFL mainly reflect the properties of the FLE.

A territorial model of commuting in Catalonia, 1986-1996

Commuting consists in the fact that an important fraction of workers in developed countries do not reside close to their workplaces but at long distances from them, so they have to travel to their jobs and then back home daily. Although most workers hold a job in the same municipality where they live or in a neighbouring one, an important fraction of workers face long daily trips to get to their workplace and then back home.Even if we divide Catalonia (Spain) in small aggregations of municipalities, trying to make them as close to local labour markets as possible, we will find out that some of them have a positive commuting balance, attracting many workers from other areas and providing local jobs for almost all their resident workers. On the other side, other zones seem to be mostly residential, so an important fraction of their resident workers hold jobs in different local labour markets. Which variables influence an area¿s role as an attraction pole or a residential zone? In previous papers (Artís et al, 1998a, 2000; Romaní, 1999) we have brought out the main individual variables that influence commuting by analysing a sample of Catalan workers and their commuting decisions. In this paper we perform an analysis of the territorial variables that influence commuting, using data for aggregate commuting flows in Catalonia from the 1991 and 1996 Spanish Population Censuses.These variables influence commuting in two different ways: a zone with a dense, welldeveloped economical structure will have a high density of jobs. Work demand cannot be fulfilled with resident workers, so it spills over local boundaries. On the other side, this economical activity has a series of side-effects like pollution, congestion or high land prices which make these areas less desirable to live in. Workers who can afford it may prefer to live in less populated, less congested zones, where they can find cheaper land, larger homes and a better quality of life. The penalty of this decision is an increased commuting time. Our aim in this paper is to highlight the influence of local economical structure and amenities endowment in the workplace-residence location decision. A place-to-place logit commuting models is estimated for 1991 and 1996 in order to find the economical and amenities variables with higher influence in commuting decisions. From these models, we can outline a first approximation to the evolution of these variables in the 1986-1996 period. Data have been obtained from aggregate flow travel-matrix from the 1986, 1991 and 1996 Spanish Population Censuses

A territorial model of commuting in Catalonia, 1986-1996

Commuting consists in the fact that an important fraction of workers in developed countries do not reside close to their workplaces but at long distances from them, so they have to travel to their jobs and then back home daily. Although most workers hold a job in the same municipality where they live or in a neighbouring one, an important fraction of workers face long daily trips to get to their workplace and then back home.Even if we divide Catalonia (Spain) in small aggregations of municipalities, trying to make them as close to local labour markets as possible, we will find out that some of them have a positive commuting balance, attracting many workers from other areas and providing local jobs for almost all their resident workers. On the other side, other zones seem to be mostly residential, so an important fraction of their resident workers hold jobs in different local labour markets. Which variables influence an area¿s role as an attraction pole or a residential zone? In previous papers (Artís et al, 1998a, 2000; Romaní, 1999) we have brought out the main individual variables that influence commuting by analysing a sample of Catalan workers and their commuting decisions. In this paper we perform an analysis of the territorial variables that influence commuting, using data for aggregate commuting flows in Catalonia from the 1991 and 1996 Spanish Population Censuses.These variables influence commuting in two different ways: a zone with a dense, welldeveloped economical structure will have a high density of jobs. Work demand cannot be fulfilled with resident workers, so it spills over local boundaries. On the other side, this economical activity has a series of side-effects like pollution, congestion or high land prices which make these areas less desirable to live in. Workers who can afford it may prefer to live in less populated, less congested zones, where they can find cheaper land, larger homes and a better quality of life. The penalty of this decision is an increased commuting time. Our aim in this paper is to highlight the influence of local economical structure and amenities endowment in the workplace-residence location decision. A place-to-place logit commuting models is estimated for 1991 and 1996 in order to find the economical and amenities variables with higher influence in commuting decisions. From these models, we can outline a first approximation to the evolution of these variables in the 1986-1996 period. Data have been obtained from aggregate flow travel-matrix from the 1986, 1991 and 1996 Spanish Population Censuses

Avalanches in a fluctuationless first-order phase transition in a random-bond Ising model

We study the behavior of the random-bond Ising model at zero temperature by numerical simulations for a variable amount of disorder. The model is an example of systems exhibiting a fluctuationless first-order phase transition similar to some field-induced phase transitions in ferromagnetic systems and the martensitic phase transition appearing in a number of metallic alloys. We focus on the study of the hysteresis cycles appearing when the external field is swept from positive to negative values. By using a finite-size scaling hypothesis, we analyze the disorder-induced phase transition between the phase exhibiting a discontinuity in the hysteresis cycle and the phase with the continuous hysteresis cycle. Critical exponents characterizing the transition are obtained. We also analyze the size and duration distributions of the magnetization jumps (avalanches).

MORM--a Petri net based model for assessing OH&S risks in industrial processes: modeling qualitative aspects.

Because of the increase in workplace automation and the diversification of industrial processes, workplaces have become more and more complex. The classical approaches used to address workplace hazard concerns, such as checklists or sequence models, are, therefore, of limited use in such complex systems. Moreover, because of the multifaceted nature of workplaces, the use of single-oriented methods, such as AEA (man oriented), FMEA (system oriented), or HAZOP (process oriented), is not satisfactory. The use of a dynamic modeling approach in order to allow multiple-oriented analyses may constitute an alternative to overcome this limitation. The qualitative modeling aspects of the MORM (man-machine occupational risk modeling) model are discussed in this article. The model, realized on an object-oriented Petri net tool (CO-OPN), has been developed to simulate and analyze industrial processes in an OH&S perspective. The industrial process is modeled as a set of interconnected subnets (state spaces), which describe its constitutive machines. Process-related factors are introduced, in an explicit way, through machine interconnections and flow properties. While man-machine interactions are modeled as triggering events for the state spaces of the machines, the CREAM cognitive behavior model is used in order to establish the relevant triggering events. In the CO-OPN formalism, the model is expressed as a set of interconnected CO-OPN objects defined over data types expressing the measure attached to the flow of entities transiting through the machines. Constraints on the measures assigned to these entities are used to determine the state changes in each machine. Interconnecting machines implies the composition of such flow and consequently the interconnection of the measure constraints. This is reflected by the construction of constraint enrichment hierarchies, which can be used for simulation and analysis optimization in a clear mathematical framework. The use of Petri nets to perform multiple-oriented analysis opens perspectives in the field of industrial risk management. It may significantly reduce the duration of the assessment process. But, most of all, it opens perspectives in the field of risk comparisons and integrated risk management. Moreover, because of the generic nature of the model and tool used, the same concepts and patterns may be used to model a wide range of systems and application fields.

How to improve flow during cardiopulmonary bypass in an acardia experimental model.

OBJECTIVES In extreme scenarios, such as hyperacute rejection of heart transplant, an urgent heart explantation might be necessary. The aim of this experimental study was to determine the feasibility and to improve the haemodynamics of a venoarterial cardiopulmonary bypass after cardiectomy. METHODS A venoarterial cardiopulmonary bypass was established in seven calves (56.4 ± 7 kg) by the transjugular insertion to the caval axis of a self-expanding cannula, with a carotid artery return. After baseline measurements (A), ventricular fibrillation was induced (B), great arteries were clamped (C), the heart was excised and the right and left atria remnants, containing the pulmonary veins, were sutured together leaving an atrial septal defect over the cannula in the caval axis (D). Measurements were taken with the pulmonary artery clamped and declamped. RESULTS Initial pump flow was 4.16 ± 0.75 l/min dropping to 2.9 ± 0.63 l/min (P(AB )< 0.001) 10 min after induction of ventricular fibrillation. After cardiectomy with the pulmonary artery clamped, the pump flow increased non-significantly to 3.20 ± 0.78 l/min. After declamping, the flow significantly increased close to baseline levels (3.61 ± 0.73 l/min, P(DB )= 0.009, P(DC )= 0.017), supporting the notion that full cardiopulmonary bypass in acardia is feasible only if adequate drainage of pulmonary circulation is assured to avoid pulmonary congestion and loss of volume from the left-to-right shunt of bronchial vessels.

Debris flow modeling for susceptibility mapping at regional to national scale in Norway

Debris flows and related landslide processes occur in many regions all over Norway and pose a significant hazard to inhabited areas. Within the framework of the development of a national debris flows susceptibility map, we are working on a modeling approach suitable for Norway with a nationwide coverage. The discrimination of source areas is based on an index approach, which includes topographic parameters and hydrological settings. For the runout modeling, we use the Flow-R model (IGAR, University of Lausanne), which is based on combined probabilistic and energetic algorithms for the assessment of the spreading of the flow and maximum runout distances. First results for different test areas have shown that runout distances can be modeled reliably. For the selection of source areas, however, additional factors have to be considered, such as the lithological and quaternary geological setting, in order to accommodate the strong variation in debris flow activity in the different geological, geomorphological and climate regions of Norway.

GIS-based debris flow source and runout susceptibility assessment from DEM data - a case study in NW Nicaragua

In October 1998, Hurricane Mitch triggered numerous landslides (mainly debris flows) in Honduras and Nicaragua, resulting in a high death toll and in considerable damage to property. The potential application of relatively simple and affordable spatial prediction models for landslide hazard mapping in developing countries was studied. Our attention was focused on a region in NW Nicaragua, one of the most severely hit places during the Mitch event. A landslide map was obtained at 1:10 000 scale in a Geographic Information System (GIS) environment from the interpretation of aerial photographs and detailed field work. In this map the terrain failure zones were distinguished from the areas within the reach of the mobilized materials. A Digital Elevation Model (DEM) with 20 m×20 m of pixel size was also employed in the study area. A comparative analysis of the terrain failures caused by Hurricane Mitch and a selection of 4 terrain factors extracted from the DEM which, contributed to the terrain instability, was carried out. Land propensity to failure was determined with the aid of a bivariate analysis and GIS tools in a terrain failure susceptibility map. In order to estimate the areas that could be affected by the path or deposition of the mobilized materials, we considered the fact that under intense rainfall events debris flows tend to travel long distances following the maximum slope and merging with the drainage network. Using the TauDEM extension for ArcGIS software we generated automatically flow lines following the maximum slope in the DEM starting from the areas prone to failure in the terrain failure susceptibility map. The areas crossed by the flow lines from each terrain failure susceptibility class correspond to the runout susceptibility classes represented in a runout susceptibility map. The study of terrain failure and runout susceptibility enabled us to obtain a spatial prediction for landslides, which could contribute to landslide risk mitigation.

Submerged Vanes for Flow Control and Bank Protection in Streams, HR-255, 1984

This study was conducted for the purpose of evaluating a new concept for a bank-protection structure: The Iowa Vane . The underlying idea involves countering the torque exerted on the primary flow by its curvature and vertical velocity gradient, thereby eliminating or significantly reducing the secondary flow and thus reducing the undermining of the outer banks and the high-velocity attack on it. The new structure consists of an array of short, vertical, submerged vanes installed with a certain orientation on the channel bed. A relatively small number of vanes can produce bend flows which are practically uniform across the channel. The height of the vanes is less than half the water depth, and their angle with the flow direction is of the order of l0 degrees. In this study, design relations have been established. The relations, and the vanes' overall performance, have been tested in a laboratory model under different flow and sediment conditions. The results are used for the design of an Iowa-Vane bank protection structure for a section of East Nishnabotna River along U.S. Highway 34 at Red Oak, Iowa.

'Heures' a bio-economic model for Mediterranean fisheries, towards the evaluation of management strategies

The bio-economic model "Heures" is a first attempt to develop a simulation procedure to understand the Northwestern Mediterranean fisheries, to evaluate management strategies and to analyze the feasibility of implementing an adaptative management. The model is built on the interaction among three boxes simulating the dynamics of each of the basic actors of a fishery: the stock, the market and the fishermen. A fourth actor, the manager, imposes or modifies the rules, or, in terms of the model, modifies some particular parameters. Thus, the model allows us to simulate and evaluate the mid-term biologic and economic effects of particular management measures. The bio-economic nature of the model is given by the interaction among the three boxes, by the market simulation and, particularly, by the fishermen behaviour. This last element confers to the model its Mediterranean"selfregulated" character. The fishermen allocate their investments to maximize fishing mortality but, having a legal effort limit, they invest in maintenance and technology in order to increase the catchability, which, as a consequence. will be function of the invested capital.