Sensitivity of Leishmania spp. to Glibenclamide and 4-Aminopiridine: A Tool for the Study of Drug Resistance Development

We have demonstrated that Leishmania spp. grown as promastigotes, are sensitive to the K+ channel inhibitors 4-aminopyridine and glibenclamide. Their host cells, the macrophages, are not affected by similar concentrations of the drugs. We have also initiated the molecular characterization of the mechanisms involved in the development of drug resistance to glibenclamide by the parasite. Therefore, we have selected experimentally and begun to characterize the Venezuelan Leishmania (Leishmania) strain, NR resistant to glibenclamide [NR(Gr)]. The analysis of genomic DNA evidenced the existence of a fragment which apparently is amplified in NR(Gr). The fragment recognized by the pgpA probe, related to the Leishmania P-glycoprotein family and which was originally isolated from L. tarentolae, showed a size polymorfism between the sensitive and the resistant strain. These results suggest that the development of resistance to glibenclamide in the strain NR(Gr) might be associated with the amplification of the ltpgpA or related gene(s)

IRM cardiaque dans le suivi des cardiopathies congénitales à l'âge adulte [Cardiac MRI in the follow-up of adult congenital cardiomyopathy patients].

Magnetic resonance imaging is a rapidly developing modality in cardiology. It offers an excellent image definition and a large field of view, allowing a more accurate morphological assessment of cardiac malformations. Due to its unique versatility and its ability to provide myocardial tissue characterization, cardiac magnetic resonance (CMR) is now recognized as a central imaging modality for a wide range of congenital heart diseases, including assessment of post-surgical cardiac anatomy, quantification of valvular disease and detection of myocardial ischemia. CMR provides useful diagnostic information without any radiation exposure, and improves the global management of patients with congenital heart disease.

Analysis and optimization of the satellite-to-plane link of an aeronautical global system

En aquest projecte s’ha analitzat i optimitzat l’enllaç satèl·lit amb avió per a un sistema aeronàutic global. Aquest nou sistema anomenat ANTARES està dissenyat per a comunicar avions amb estacions base mitjançant un satèl·lit. Aquesta és una iniciativa on hi participen institucions oficials en l’aviació com ara l’ECAC i que és desenvolupat en una col·laboració europea d’universitats i empreses. El treball dut a terme en el projecte compren bàsicament tres aspectes. El disseny i anàlisi de la gestió de recursos. La idoneïtat d’utilitzar correcció d’errors en la capa d’enllaç i en cas que sigui necessària dissenyar una opció de codificació preliminar. Finalment, estudiar i analitzar l’efecte de la interferència co-canal en sistemes multifeix. Tots aquests temes són considerats només per al “forward link”. L’estructura que segueix el projecte és primer presentar les característiques globals del sistema, després centrar-se i analitzar els temes mencionats per a poder donar resultats i extreure conclusions.

Ciudades que contribuyen a la sostenibilidad global

Trabajos anteriores han demostrado que gran parte de la variabilidad observada en la huella ecológica per cápita de los países puede explicarse a partir de las diferencias en renta per cápita y temperatura. La pregunta que nos planteamos en esta investigación es si el modelo urbano (densidad urbana y tamaño urbano) también puede ayudar a explicar dicha variabilidad. Los resultados obtenidos confirman el significativo impacto de la densidad urbana sobre la huella, por lo que controlar la dispersión urbana parece ser un mecanismo eficiente para reducir la huella ecológica de los países. En lugar de reflexionar sobre si las ciudades son o no son insostenibles por naturaleza, esta investigación se ha orientado de forma más operativa, intentando discernir qué tipo de modelo urbano contribuye en mayor medida a la sostenibilidad del planeta.

Local and global consistency properties for student placement

In the context of resource allocation on the basis of priorities, Ergin (2002) identifies a necessary and sufficient condition on the priority structure such that the student-optimal stable mechanism satisfies a consistency principle. Ergin (2002) formulates consistency as a local property based on a fixed population of agents and fixed resources -- we refer to this condition as local consistency and to his condition on the priority structure as local acyclicity. We identify a related but stronger necessary and sufficient condition (unit acyclicity) on the priority structure such that the student-optimal stable mechanism satisfies a more standard global consistency property. Next, we provide necessary and sufficient conditions for the student-optimal stable mechanism to satisfy converse consistency principles. We identify a necessary and sufficient condition (local shift-freeness) on the priority structure such that the student-optimal stable mechanism satisfies local converse consistency. Interestingly, local acyclicity implies local shift-freeness and hence the student-optimal stable mechanism more frequently satisfies local converse consistency than local consistency. Finally, in order for the student-optimal stable mechanism to be globally conversely consistent, one again has to impose unit acyclicity on the priority structure. Hence, unit acyclicity is a necessary and sufficient condition on the priority structure for the student-optimal stable mechanism to satisfy global consistency or global converse consistency.

Nivell global d'estrès en pares i mares de fills diagnosticats amb trastorn del desenvolupament en les primeres etapes evolutives

Aquest treball és un estudi descriptiu centralitzat en una població concreta i en un moment concret. La investigació estudia el nivell d’estrès global que tenen els pares i les mares de fills/es amb un trastorn del seu desenvolupament en les seves primeres edats maduratives i com afronten aquest procés. S’han estudiat pares i mares de nens i nenes d’entre 2 i 6 anys d’edat i que han estat atesos en el Centre de Desenvolupament Infantil d’Atenció Precoç (CDIAP) Tris-Tras de Vic (Barcelona).

A correlation sensitivity analysis of non-life underwriting risk in solvency capital requirement estimation

This paper analyses the impact of using different correlation assumptions between lines of business when estimating the risk-based capital reserve, the Solvency Capital Requirement (SCR), under Solvency II regulations. A case study is presented and the SCR is calculated according to the Standard Model approach. Alternatively, the requirement is then calculated using an Internal Model based on a Monte Carlo simulation of the net underwriting result at a one-year horizon, with copulas being used to model the dependence between lines of business. To address the impact of these model assumptions on the SCR we conduct a sensitivity analysis. We examine changes in the correlation matrix between lines of business and address the choice of copulas. Drawing on aggregate historical data from the Spanish non-life insurance market between 2000 and 2009, we conclude that modifications of the correlation and dependence assumptions have a significant impact on SCR estimation.

Pioglitazone improves fat distribution, the adipokine profile and hepatic insulin sensitivity in non-diabetic end-stage renal disease subjects on maintenance dialysis: a randomized cross-over pilot study.

BACKGROUND: Fat redistribution, increased inflammation and insulin resistance are prevalent in non-diabetic subjects treated with maintenance dialysis. The aim of this study was to test whether pioglitazone, a powerful insulin sensitizer, alters body fat distribution and adipokine secretion in these subjects and whether it is associated with improved insulin sensitivity. TRIAL DESIGN: This was a double blind cross-over study with 16 weeks of pioglitazone 45 mg vs placebo involving 12 subjects. METHODS: At the end of each phase, body composition (anthropometric measurements, dual energy X-ray absorptometry (DEXA), abdominal CT), hepatic and muscle insulin sensitivity (2-step hyperinsulinemic euglycemic clamp with 2H2-glucose) were measured and fasting blood adipokines and cardiometabolic risk markers were monitored. RESULTS: Four months treatment with pioglitazone had no effect on total body weight or total fat but decreased the visceral/sub-cutaneous adipose tissue ratio by 16% and decreased the leptin/adiponectin (L/A) ratio from 3.63×10-3 to 0.76×10-3. This was associated with a 20% increase in hepatic insulin sensitivity without changes in muscle insulin sensitivity, a 12% increase in HDL cholesterol and a 50% decrease in CRP. CONCLUSIONS/LIMITATIONS: Pioglitazone significantly changes the visceral-subcutaneous fat distribution and plasma L/A ratio in non diabetic subjects on maintenance dialysis. This was associated with improved hepatic insulin sensitivity and a reduction of cardio-metabolic risk markers. Whether these effects may improve the outcome of non diabetic end-stage renal disease subjects on maintenance dialysis still needs further evaluation. TRIAL REGISTRATION: ClinicalTrial.gov NCT01253928.

Local-global splitting for spatiotemporal-adaptive multiscale methods

We present a novel spatiotemporal-adaptive Multiscale Finite Volume (MsFV) method, which is based on the natural idea that the global coarse-scale problem has longer characteristic time than the local fine-scale problems. As a consequence, the global problem can be solved with larger time steps than the local problems. In contrast to the pressure-transport splitting usually employed in the standard MsFV approach, we propose to start directly with a local-global splitting that allows to locally retain the original degree of coupling. This is crucial for highly non-linear systems or in the presence of physical instabilities. To obtain an accurate and efficient algorithm, we devise new adaptive criteria for global update that are based on changes of coarse-scale quantities rather than on fine-scale quantities, as it is routinely done before in the adaptive MsFV method. By means of a complexity analysis we show that the adaptive approach gives a noticeable speed-up with respect to the standard MsFV algorithm. In particular, it is efficient in case of large upscaling factors, which is important for multiphysics problems. Based on the observation that local time stepping acts as a smoother, we devise a self-correcting algorithm which incorporates the information from previous times to improve the quality of the multiscale approximation. We present results of multiphase flow simulations both for Darcy-scale and multiphysics (hybrid) problems, in which a local pore-scale description is combined with a global Darcy-like description. The novel spatiotemporal-adaptive multiscale method based on the local-global splitting is not limited to porous media flow problems, but it can be extended to any system described by a set of conservation equations.

The stabilizing effects of the acquired immunity on the schistosomiasis transmission modeling - the sensitivity Analysis

A mathematical model is proposed to analyze the effects of acquired immunity on the transmission of schistosomiasis in the human host. From this model the prevalence curve dependent on four parameters can be obtained. These parameters were estimated fitting the data by the maximum likelihood method. The model showed a good retrieving capacity of real data from two endemic areas of schistosomiasis: Touros, Brazil (Schistosoma mansoni) and Misungwi, Tanzania (S. haematobium). Also, the average worm burden per person and the dispersion of parasite per person in the community can be obtained from the model. In this paper, the stabilizing effects of the acquired immunity assumption in the model are assessed in terms of the epidemiological variables as follows. Regarded to the prevalence curve, we calculate the confidence interval, and related to the average worm burden and the worm dispersion in the community, the sensitivity analysis (the range of the variation) of both variables with respect to their parameters is performed.

Turnaround across diverse global supply chains using shared metrics and change methodology: The Case of Amer Sports Corporation

Purpose - The purpose of this paper is to document the outcome of a global three-year long supply chain improvement initiative at a multi-national producer of branded sporting goods that is transforming from a holding structure to an integrated company. The case company is comprised of seven internationally well-known sport brands, which form a diverse set of independent sub-cases, on which the same supply chain metrics and change project approach was applied to improve supply chain performance. Design/methodology/approach - By using in-depth case study and statistical analysis the paper analyzes across the brands how supply chain complexity (SKU count), supply chain type (make or buy) and seasonality affect completeness and punctuality of deliveries, and inventory as the change project progresses. Findings - Results show that reduction in supply chain complexity improves delivery performance, but has no impact on inventory. Supply chain type has no impact on service level, but brands with in-house production are better in improving inventory than those with outsourced production. Non-seasonal business units improve service faster than seasonal ones, yet there is no impact on inventory. Research limitations/implications - The longitudinal data used for the analysis is biased with the general business trend, yet the rich data from different cases and three-years of data collection enables generalizations to a certain level. Practical implications - The in-depth case study serves as an example for other companies on how to initiate a supply chain improvement project across business units with tangible results. Originality/value - The seven sub-cases with their different characteristics on which the same improvement initiative was applied sets a unique ground for longitudinal analysis to study supply chain complexity, type and seasonality.

The global uranium rush and its Africa frontier. Lessons from Namibia

Uranium mines are the - often forgotten - source of nuclear power. The promotion of nuclear energy as a clean alternative and the projected increase of electricity demand in countries such as China and India, have led to a global “uranium rush”, unseen since the peak of the Cold War. This article studies the formation of the expanding nuclear frontier looking at the interaction between the global uranium metabolism, industrial dynamics and local ecologies of resistance using Namibia as a case-study. Namibia, the world´s fourth largest producer of uranium, stands at the frontier of this rush with sixty-six recently granted prospecting licenses that could turn into mines, compared to only three currently operating mines. We focus on three generic attributes that help to explain the emergence and intensity of resistance by local communities to uranium mining: the ecology and geography of the resource; the degree and type of political and economic marginalization of the community; and crucially, the connection and integration of local concerns with broader social movements and political demands. We show with the use of empirical material how these factors play out differently in five Namibian communities that have been, or stand to be, affected by uranium mining, and explain how local ecologies of resistance shape the global uranium rush.