Connection of Dynamic Quality Modeling and Total Service Management in Railway Transport Operation

Improving the quality of transport services should be based on the procedure leading to the formation of future better services and define processes to ensure quality so that they comply with the requirements of the customers. The technology of transport and carriage process is one of the elements of the transport system, the quality of which can be influenced actively through the use of new advanced technology. This paper is focused on the new approach in designing the preparation of processes and services in accordance with customer''s needs. New software solution was created for the achievement of the complexity of the preparation, effective implementation and timely indication of any diversions from quality in railway transport. The principles of the dynamic quality modeling and total service management were used as an important support for new software in railway transport operation

Urbanismo neoliberal y fragmentación urbana: El caso de Zaragoza (España) en los primeros quince años del siglo XXI

El crecimiento del espacio urbano de Zaragoza durante los primeros quince años del siglo xxi se caracteriza por su fragmentación socioespacial a varias escalas, un rasgo significativo del urbanismo neoliberal. En esta ciudad se ha seguido un modelo que se compone por grandes fragmentos monofuncionales, no separados unos de otros, sino soldados al espacio urbano preexistente por las principales arterias de circulación; estas vías y otros obstáculos físicos o percibidos interrumpen la continuidad con el espacio consolidado, sobre todo para el movimiento de personas. No obstante este patrón permite la conexión de los nuevos espacios con el entorno urbano local, al mismo tiempo fomenta la segregación social e impulsa un modelo policéntrico basado en desplazamientos en automóvil privado. The growth of urban space of Zaragoza during the first fifteen years of the 21st century is characterized by its socio-spatial fragmentation at several scales, a significant feature of the neoliberal urbanism. The growth model of the city is composed of large monofunctional urban fragments attached to the existing urban space by the main traffic routes. These ways and other physical or perceived obstacles interrupt the continuity with the consolidated urban space, especially for the movement of people. Nevertheless, this pattern allows the connection of the new spaces with the local urban environment but, at the same time, promotes the social segregation and fosters a polycentric functional model based on travel by private car

Concurrencia en torno a la planificación estratégica urbana. Análisis, aprendizajes y sinergias de la estrategia Zaragoza +20

Este trabajo analiza la Estrategia Zaragoza +20, marco de planificación estratégica que contiene las directrices para la intervención en la ciudad de Zaragoza (España) y su entorno metropolitano en los próximos años. En el contexto de la Planificación Estratégica Urbana, se describen los antecedentes y se revisa críticamente la metodología y enfoques empleados para la formulación del plan. La Estrategia se alinea con las principales agendas urbanas nacionales e internacionales, lo que supone uno de los primeros ejemplos en la planificación de las ciudades españolas..

Effectiveness and safety of first-generation protease inhibitors in clinical practice: Hepatitis C virus patients with advanced fibrosis

AIM: To evaluates the effectiveness and safety of the first generation, NS3/4A protease inhibitors (PIs) in clinical practice against chronic C virus, especially in patients with advanced fibrosis. METHODS: Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1, treatment-nai¨ve (TN) or treatment-experienced (TE), who underwent triple therapy with the first generation NS3/4A protease inhibitors, boceprevir (BOC) and telaprevir (TVR), in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow up. RESULTS: One thousand and fifty seven patients were included, 405 (38%) were treated with BOC and 652 (62%) with TVR. Of this total, 30% (n = 319) were TN and the remaining were TE: 28% (n = 298) relapsers, 12% (n = 123) partial responders (PR), 25% (n = 260) null-responders (NR) and for 5% (n = 57) with prior response unknown. The rate of sustained virologic response (SVR) by intention-to-treatment (ITT) was greater in those treated with TVR (65%) than in those treated with BOC (52%) (P < 0.0001), whereas by modified intention-to-treatment (mITT) no were found significant differences. By degree of fibrosis, 56% of patients were F4 and the highest SVR rates were recorded in the non-F4 patients, both TN and TE. In the analysis by groups, the TN patients treated with TVR by ITT showed a higher SVR (P = 0.005). However, by mITT there were no significant differences between BOC and TVR. In the multivariate analysis by mITT, the significant SVR factors were relapsers, IL28B CC and non-F4; the type of treatment (BOC or TVR) was not significant. The lowest SVR values were presented by the F4-NR patients, treated with BOC (46%) or with TVR (45%). 28% of the patients interrupted the treatment, mainly by non-viral response (51%): this outcome was more frequent in the TE than in the TN patients (57% vs 40%, P = 0.01). With respect to severe haematological disorders, neutropaenia was more likely to affect the patients treated with BOC (33% vs 20%, P = 0.0001), and thrombocytopaenia and anaemia, the F4 patients (P = 0.000, P = 0.025, respectively). CONCLUSION: In a real clinical practice setting with a high proportion of patients with advanced fibrosis, effectiveness of first-generation PIs was high except for NR patients, with similar SVR rates being achieved by BOC and TVR

Heme-Regulated eIF2α Kinase Modulates Hepatic FGF21 and Is Activated by PPARβ/δ Deficiency.

Fibroblast growth factor 21 (FGF21), a peptide hormone with pleiotropic effects on carbohydrate and lipid metabolism, is considered a target for the treatment of diabetes. We investigated the role of peroxisome proliferator-activated receptor (PPAR) β/δ deficiency in hepatic FGF21 regulation. Increased Fgf21 expression was observed in the livers of PPARβ/δ-null mice and in mouse primary hepatocytes when this receptor was knocked down by small interfering RNA (siRNA). Increased Fgf21 was associated with enhanced protein levels in the heme-regulated eukaryotic translation initiation factor 2α (eIF2α) kinase (HRI). This increase caused enhanced levels of phosphorylated eIF2α and activating transcription factor (ATF) 4, which is essential for Fgf21-induced expression. siRNA analysis demonstrated that HRI regulates Fgf21 expression in primary hepatocytes. Enhanced Fgf21 expression attenuated tunicamycin-induced endoplasmic reticulum stress, as demonstrated by using a neutralizing antibody against FGF21. Of note, increased Fgf21 expression in mice fed a high-fat diet or hepatocytes exposed to palmitate was accompanied by reduced PPARβ/δ and activation of the HRI-eIF2α-ATF4 pathway. Moreover, pharmacological activation of HRI increased Fgf21 expression and reduced lipid-induced hepatic steatosis and glucose intolerance, but these effects were not observed in Fgf21-null mice. Overall, these findings suggest that HRI is a potential target for regulating hepatic FGF21 levels

Plasma membrane calcium ATPase isoform 4 inhibits vascular endothelial growth factor-mediated angiogenesis through interaction with calcineurin.

Vascular endothelial growth factor (VEGF) has been identified as a crucial regulator of physiological and pathological angiogenesis. Among the intracellular signaling pathways triggered by VEGF, activation of the calcineurin/nuclear factor of activated T cells (NFAT) signaling axis has emerged as a critical mediator of angiogenic processes. We and others previously reported a novel role for the plasma membrane calcium ATPase (PMCA) as an endogenous inhibitor of the calcineurin/NFAT pathway, via interaction with calcineurin, in cardiomyocytes and breast cancer cells. However, the functional significance of the PMCA/calcineurin interaction in endothelial pathophysiology has not been addressed thus far. Using in vitro and in vivo assays, we here demonstrate that the interaction between PMCA4 and calcineurin in VEGF-stimulated endothelial cells leads to downregulation of the calcineurin/NFAT pathway and to a significant reduction in the subsequent expression of the NFAT-dependent, VEGF-activated, proangiogenic genes RCAN1.4 and Cox-2. PMCA4-dependent inhibition of calcineurin signaling translates into a reduction in endothelial cell motility and blood vessel formation that ultimately impairs in vivo angiogenesis by VEGF. Given the importance of the calcineurin/NFAT pathway in the regulation of pathological angiogenesis, targeted modulation of PMCA4 functionality might open novel therapeutic avenues to promote or attenuate new vessel formation in diseases that occur with angiogenesis