Assessorament als agents de la policia local de Montmeló en el marc de les intervencions d'educació viària i mobilitat segura que imparteixen als diferents centres educatius de la localitat

En aquesta memòria de pràctiques es desenvolupa el projecte que s'ha portat a terme durant els darrers tres mesos en el Departament d'Educació Viària de la policia local de Montmeló. El projecte s'ha aplicat, per mitjà de l'assessorament als agents, amb la finalitat de proporcionar-los unes eines bàsiques perquè en el futur puguin revisar i modificar les seves intervencions educatives o dissenyar-ne unes altres de noves, d'una manera molt més ajustada i totalment autònoma.

Onychomycosis insensitive to systemic terbinafine and azole treatments reveals non-dermatophyte moulds as infectious agents.

BACKGROUND: Dermatophytes are the main cause of onychomycoses, but various non-dermatophyte filamentous fungi are often isolated from abnormal nails. OBJECTIVE: Our aim was the in situ identification of the fungal infectious agent in 8 cases of onychomycoses which could not be cured after systemic terbinafine and itraconazole treatment. METHODS: Fungal DNA was extracted from nail samples, and infectious fungi were identified by restriction fragment length polymorphism (RFLP) of amplified fungal ribosomal DNA using a previously described PCR/RFLP assay. RESULTS: PCR/RFLP identification of fungi in nails allows the identification of the infectious agent: Fusarium sp., Acremonium sp. and Aspergillus sp. were found as a sole infectious agent in 5, 2 and 1 cases, respectively. CONCLUSIONS: Fusarium spp. and other non-dermatophyte filamentous fungi are especially difficult to cure in onychomycoses utilising standard treatment with terbinafine and itraconazole. PCR fungal identification helps demonstrate the presence of moulds in order to prescribe alternative antifungal treatments.

Morphological and biochemical characterization of the aetiological agents of white piedra

The Trichosporon genus is constituted by many species, of which Trichosporon ovoides and Trichosporon inkin are the causative agents of white piedra. They can cause nodules in genital hair or on the scalp. At present, Brazilian laboratory routines generally do not include the identification of the species of Trichosporon genus, which, although morphologically and physiologically distinct, present many similarities, making the identification difficult. The aim of this study was to identify the aetiological agents at the species level of white piedra from clinical specimens. Therefore, both the macro and micro morphology were studied, and physiological tests were performed. Trichosporon spp. was isolated from 10 clinical samples; T. ovoides was predominant, as it was found in seven samples, while T. inkin was identified just in two samples. One isolate could not be identified at the species level. T. inkin was identified for the first time as a white piedra agent in the hair shaft on child under the age of 10.

Genotyping of the MTL loci and susceptibility to two antifungal agents of Candida glabrata clinical isolates

The opportunistic fungal pathogen Candida glabrata is the second most common isolate from bloodstream infections worldwide and is naturally less susceptible to the antifungal drug fluconazole than other Candida species. C. glabrata is a haploid yeast that contains three mating-type like loci (MTL), although no sexual cycle has been described. Strains containing both types of mating information at the MTL1 locus are found in clinical isolates, but it is thought that strains containing type a information are more common. Here we investigated if a particular combination of mating type information at each MTLlocus is more prevalent in clinical isolates from hospitalized patients in Mexico and if there is a correlation between mating information and resistance to fluconazole and 5-fluorocytosine. We found that while both types of information at MTL1 are equally represented in a collection of 64 clinical isolates, the vast majority of isolates contain a-type information at MTL2 and α-type at MTL3. We also found no correlation of the particular combination of mating type information at the three MTL loci and resistance to fluconazole.

Appropriate end-points for right results in the age of antiangiogenic agents: Future options for phase II trials in patients with recurrent glioblastoma.

The progression-free survival rate at 6months (PFS-6) has long been considered the best end-point for assessing the efficacy of new agents in phase II trials in patients with recurrent glioblastoma. However, due to the introduction of antiangiogenic agents in this setting, and their intrinsic propensity to alter neuroradiological disease assessment by producing pseudoregression, any end-point based on neuroradiological modifications should be reconsidered. Further, statistically significant effects on progression-free survival (PFS) only should not automatically be considered reliable evidence of meaningful clinical benefit. In this context, because of its direct and unquestionable clinical relevance, overall survival (OS) represents the gold standard end-point for measuring clinical efficacy, despite the disadvantage that it is influenced by subsequent therapies and usually takes longer time to be evaluated. Therefore, while awaiting novel imaging criteria for response evaluation and/or new imaging tools to distinguish between 'true' and 'pseudo'-responses to antiangiogenic agents, the measurement of OS or OS rates should be considered primary end-points, also in phase II trials with these agents.

Automatic self-configuration of the logical network using distributed software agents

We present a system for dynamic network resource configuration in environments with bandwidth reservation. The proposed system is completely distributed and automates the mechanisms for adapting the logical network to the offered load. The system is able to manage dynamically a logical network such as a virtual path network in ATM or a label switched path network in MPLS or GMPLS. The system design and implementation is based on a multi-agent system (MAS) which make the decisions of when and how to change a logical path. Despite the lack of a centralised global network view, results show that MAS manages the network resources effectively, reducing the connection blocking probability and, therefore, achieving better utilisation of network resources. We also include details of its architecture and implementation

Dynamic bandwidth management as part of an integrated network management system based on distributed agents

We present a system for dynamic network resource configuration in environments with bandwidth reservation and path restoration mechanisms. Our focus is on the dynamic bandwidth management results, although the main goal of the system is the integration of the different mechanisms that manage the reserved paths (bandwidth, restoration, and spare capacity planning). The objective is to avoid conflicts between these mechanisms. The system is able to dynamically manage a logical network such as a virtual path network in ATM or a label switch path network in MPLS. This system has been designed to be modular in the sense that in can be activated or deactivated, and it can be applied only in a sub-network. The system design and implementation is based on a multi-agent system (MAS). We also included details of its architecture and implementation

Susceptibility of Mycobacterium tuberculosis to first-line antimycobacterial agents in a Brazilian hospital: assessing the utility of the tetrazolium (MTT) microplate assay

We conducted a cross-sectional, hospital-based study between January 2006-March 2008 to estimate the resistance of Mycobacterium tuberculosis to first-line drugs in patients with tuberculosis at a Brazilian hospital. We evaluated the performance of the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] (MTT) microplate assay compared with the Bactec-MGIT 960™ system for mycobacteria testing. The prevalence of resistance in M. tuberculosis was 6.7%. Multidrug-resistance [resistance to rifampicin (RMP) and isoniazid (INH)], INH-resistance and streptomycin (SM)-resistance accounted for 1%, 3.8% and 3.8% of all resistance, respectively, and all isolates were susceptible to ethambutol (EM). The resistance was primary in four cases and acquired in three cases and previous treatment was associated with resistance (p = 0.0129). Among the 119 M. tuberculosis isolates, complete concordance of the results for INH and EM was observed between the MTT microplate and Bactec-MGIT 960TM methods. The observed agreement for RMP was 99% (sensitivity: 90%) and 95.8% for SM (sensitivity 90.9%), lower than those for other drugs. The MTT colourimetric method is an accurate, simple and low-cost alternative in settings with limited resources.

Interacting software-agents to support a kind of expert supervision systems

Expert supervision systems are software applications specially designed to automate process monitoring. The goal is to reduce the dependency on human operators to assure the correct operation of a process including faulty situations. Construction of this kind of application involves an important task of design and development in order to represent and to manipulate process data and behaviour at different degrees of abstraction for interfacing with data acquisition systems connected to the process. This is an open problem that becomes more complex with the number of variables, parameters and relations to account for the complexity of the process. Multiple specialised modules tuned to solve simpler tasks that operate under a co-ordination provide a solution. A modular architecture based on concepts of software agents, taking advantage of the integration of diverse knowledge-based techniques, is proposed for this purpose. The components (software agents, communication mechanisms and perception/action mechanisms) are based on ICa (Intelligent Control architecture), software middleware supporting the build-up of applications with software agent features

Embodied Autonomy in Digital Ecosystems: From Bio-Inspired Agents to Cognitive Systems

This paper proposes to promote autonomy in digital ecosystems so that it provides agents with information to improve the behavior of the digital ecosystem in terms of stability. This work proposes that, in digital ecosystems, autonomous agents can provide fundamental services and information. The final goal is to run the ecosystem, generate novel conditions and let agents exploit them. A set of evaluation measures must be defined as well. We want to provide an outline of some global indicators, such as heterogeneity and diversity, and establish relationships between agent behavior and these global indicators to fully understand interactions between agents, and to understand the dependence and autonomy relations that emerge between the interacting agents. Individual variations, interaction dependencies, and environmental factors are determinants of autonomy that would be considered. The paper concludes with a discussion of situations when autonomy is a milestone

Evaluation of the synergistic potential of vancomycin combined with other antimicrobial agents against methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus spp strains

Methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative Staphylococcus spp (CNS) are the most common pathogens that cause serious long term infections in patients. Despite the existence of new antimicrobial agents, such as linezolid, vancomycin (VAN) remains the standard therapy for the treatment of infections caused by these multidrug-resistant strains. However, the use of VAN has been associated with a high frequency of therapeutic failures in some clinical scenarios, mainly with decreasing concentration of VAN. This work aims to evaluate the synergic potential of VAN plus sulfamethoxazole/trimethoprim (SXT), VAN plus rifampin (RIF) and VAN plus imipenem (IPM) in sub-minimum inhibitory concentrations against 22 clinical strains of MRSA and CNS. The checkerboard method showed synergism of VAN/RIF and VAN/SXT against two and three of the 22 strains, respectively. The combination of VAN with IPM showed synergistic effects against 21 out of 22 strains by the E-test method. Four strains were analyzed by the time-kill curve method and synergistic activity was observed with VAN/SXT, VAN/RIF and especially VAN/IPM in sub-inhibitory concentrations. It would be interesting to determine if synergy occurs in vivo. Evidence of in vivo synergy could lead to a reduction of the standard VAN dosage or treatment time.

Improving anemia management with less frequently dosed erythropoiesis stimulating agents

Introduction and Aims: The process of delivering erythropoiesis stimulating agents (ESAs) to hemodialysis patients (HD) is complex. Many European countries are requiring centers to document this process. To date, there has not been any comprehensive description of the operational aspects of ESA delivery in Europe. The objective of the Mercurius study was to describe the entire process of ESA delivery in dialysis centers. In addition, we explored the benefits of less frequent dosing. Methods: A conceptual model was developed to classify the sub-processes in the pharmacy, dialysis unit, waste unit, and back office. Within each dialysis unit activities associated with dose determination, ordering procedures, receipt and storage of ESAs, and ESA administration were measured. Within the pharmacy, ordering from supplier, receiving and storing, and delivering ESA to the dialysis unit were measured. The amount of time and materials associated with waste disposal and back office activities were also observed. We also evaluated the impact of less frequent dosing on the resources required to perform anemia management for HD patients. Structured interviews with staff were used to develop a comprehensive list of processes, sub-processes, and activities that are routinely followed to order, register, administer, and dispose of waste associated with ESAs. Each activity was evaluated to determine if less frequent dosing influenced the amount of resources required. A model was developed to estimate the change in resources consumed using less frequent dosing regimens. Results: Eight centers from 5 European countries (Belgium, France, Italy, Sweden, and Switzerland) participated in the study. The number of HD patients in each center ranged from 42 to 707 (mean=175). Across all of the centers, patients received a variety of dosing regimens (eg, TIW, BIW, QW and Q2W). The mean (±SD) time spent for the pharmacy to order an ESA from the supplier was 6.1 (±8.7) minutes; time spent in the dialysis unit and pharmacy for receiving and storing ESPs was 5.3 (±5.3) and 10.0 (±10.9) minutes, respectively; and time spent administering each injection was 6.4 (±6.5) minutes. Switching from current dosing practices to Q2W could decrease the mean number of syringes used from 12,420 to 5,085 per year. We estimate a reduction in the number of disinfective tissues and liquids of 58% and 71%, respectively by switching from current practice to dosing ESAs Q2W. Conclusions: There was significant variation in the time that it takes to perform routine ESA activities. We estimate that a reduction in resources required to manage anemia can be obtained by reducing the frequency of administration from the current mix of ESAs. These resources could be redeployed for patient care.

Anàlisi de la imatge turística percebuda pels agents orgànics: El cas de Girona

Anàlisi empírica de la imatge turística de la ciutat de Girona que transmeten els agents orgànics mitjançant els blogs d’Internet i, a partir d’aquí, deducció de quina és la imatge percebuda pels turistes potencials

Genotypes of Cryptococcus neoformans and Cryptococcus gattii as agents of endemic cryptococcosis in Teresina, Piauí (northeastern Brazil)

Throughout Brazil, Cryptococcus neoformans is the cause of cryptococcosis, whereas Cryptococcus gattii is endemic to the northern and northeastern states. In this study, the molecular types of 63 cryptococcal isolates recovered from the cerebrospinal fluid of meningitis patients diagnosed between 2008-2010 in Teresina, Piauí, Brazil, were analysed. Out of the 63 patients, 37 (58.7%) were human immunodeficiency virus (HIV)-positive and 26 (41.3%) were HIV-negative. URA5-restriction fragment length polymorphism analysis identified 37/63 (58.7%) isolates as the C. neoformans VNI genotype, predominantly in HIV-positive patients (32/37, 86.5%), and 24/63 (38.1%) as the C. gattii VGII genotype, mostly in HIV-negative patients (21/26, 80.8%). The occurrence of C. gattii VGII in six apparently healthy children and in seven adolescents/young adults in this region reaffirms the endemic occurrence of C. gattii VGII-induced primary cryptococcosis and early cryptococcal infection. Lethality occurred in 18/37 (48.6%) of the HIV-positive subjects and in 13/26 (50%) of the HIV-negative patients. Our results provide new information on the molecular epidemiology of C. neoformans and C. gattii in Brazilian endemic areas.

Analysis of GPCR properties of Frizzled receptors and establishment of the "in vitro" platform for screening of Frizzled agonists/antagonists as potential therapeutic agents

Morphogens of the Wnt protein family are the secreted lipoglycoprotein ligands which initiate several pathways heavily involved in the coordination of various developmental stages of organisms in the majority of animal species. Deregulation of these pathways in the adult leads to formation and sustaining of multiple types of cancer. The latter notion is reinforced by the fact that the very discovery of the first Wnt ligand was due to its role as the causative factor of carcinogenic transformation (Nusse and Varmus, 1982). Nowadays our knowledge on Wnt signaling has "moved with the times" and these pathways were identified to be often crucial for tumor formation, its interactions with the microenvironment, and promotion of the metastases (Huang and Du, 2008; Zerlin et al., 2008; Jessen, 2009). Thus the relevance of the pathway as the target for drug development has further increased in the light of modern paradigms of the complex cancer treatments which target also spreading and growth- promoting factors of tumors by specific and highly efficient substances (Pavet et al., 2010). Presently the field of the Wnt-targeting drug research is almost solely dominated by assays based on transcriptional activation induced by the signaling. This approach resulted in development of a number of promising substances (Lee et al., 2011). Despite its effectiveness, the method nevertheless suffers from several drawbacks. Among the major ones is the fact that this approach is prone to identify compounds targeting rather downstream effectors of the pathway, which are indiscriminately used by all the subtypes of the Wnt signaling. Additionally, proteins which are involved in several signaling cascades and not just the Wnt pathway turn out as targets of the new compounds. These issues increase risks of side effects due to off-target interactions and blockade of the pathway in healthy cells. In the present work we put forward a novel biochemical approach for drug development on the Wnt pathway. It targets Frizzleds (Fzs) - a family of 7-transmbembrane proteins which serve as receptors for Wnt ligands. They offer unique properties for the development of highly specific and effective drugs as they control all branches of the Wnt signaling. Recent advances in the understanding of the roles of heterotrimeric G proteins downstream from Fzs (Katanaev et al., 2005; Liu et al., 2005; Jernigan et al., 2010) suggest application of enzymatic properties of these effectors to monitor the receptor-mediated events. We have applied this knowledge in practice and established a specific and efficient method based on utilization of a novel high-throughput format of the GTP-binding assay to follow the activation of Fzs. This type of assay is a robust and well-established technology for the research and screenings on the GPCRs (Harrison and Traynor, 2003). The conventional method of detection involves the radioactively labeled non-hydrolysable GTP analog [35S]GTPyS. Its application in the large-scale screenings is however problematic which promoted development of the novel non-radioactive GTP analog GTP-Eu. The new molecule employs phenomenon of the time-resolved fluorescence to provide sensitivity comparable to the conventional radioactive substance. Initially GTP-Eu was tested only in one of many possible types of GTP-binding assays (Frang et al., 2003). In the present work we expand these limits by demonstrating the general comparability of the novel label with the radioactive method in various types of assays. We provide a biochemical characterization of GTP-Eu interactions with heterotrimeric and small GTPases and a comparative analysis of the behavior of the new label in the assays involving heterotrimeric G protein effectors. These developments in the GTP-binding assay were then applied to monitor G protein activation by the Fz receptors. The data obtained in mammalian cultured cell lines provides for the first time an unambiguous biochemical proof for direct coupling of Fzs with G proteins. The specificity of this interaction has been confirmed by the experiments with the antagonists of Fz and by the pertussis toxin-mediated deactivation. Additionally we have identified the specificity of Wnt3a towards several members of the Fz family and analyzed the properties of human Fz-1 which was found to be the receptor coupled to the Gi/o family of G proteins. Another process playing significant role in the functioning of every GPCR is endocytosis. This phenomenon can also be employed for drug screenings on GPCRs (Bickle, 2010). In the present work we have demonstrated that Drosophila Fz receptors are involved in an unusual for many GPCRs manifestation of the receptor-mediated internalization. Through combination of biochemical approaches and studies on Drosophila as the model organism we have shown that direct interactions of the Fzs and the α-subunit of the heterotrimeric G protein Go with the small GTPase Rab5 regulate internalization of the receptor in early endosomes. We provide data uncovering the decisive role of this self-promoted endocytosis in formation of a proper signaling output in the canonical as well as planar cell polarity (PCP) pathways regulated by Fz. The results of this work thus establish a platform for the high-throughput screening to identify substances active in the cancer-related Wnt pathways. This methodology has been adjusted and applied to provide the important insights in Fz functioning and will be instrumental for further investigations on the Wnt-mediated pathways.