El marketing relacional y la rentabilidad en los servicios prestados por tres concesionarios automotrices en la provincia de Tungurahua del Ecuador.

El objetivo del presente trabajo consistió en identificar la relación existente entre la lealtad de clientes como factor clave del marketing relacional y la evolución de la rentabilidad neta alcanzada en los Talleres de Servicios durante los años 2012 al 2014 en tres concesionarios automotrices de la Provincia de Tungurahua en el Ecuador. Los resultados obtenidos respecto a la medición de la lealtad de los clientes se evaluaron a través de dos dimensiones, la rotación de clientes y el índice de satisfacción de los mismos, como indicadores de medición de lealtad, por otro lado, la rentabilidad neta se analizó tomando en consideración el resultado operativo frente al total de ingresos alcanzados durante el período de estudio. A través del estudio cuantitativo apoyado en el análisis estadístico correlacional y el coeficiente de determinación se analizaron los datos disponibles en las mencionadas empresas y se identificó una alta dependencia de las acciones relativas al marketing relacional desarrolladas por las empresas de manera sistemática durante el período estudiado y los resultados financieros netos del área de servicios mecánicos especializados de los concesionarios automotrices

Tracking and understanding phase progression in Lisa`s case

This study adds a phase‐by‐phase perspective to the well‐known, and thoroughly analysed on a moment‐by‐moment basis, case of Lisa. The aim is to see whether this phase‐by‐phase analysis adds anything valuable to the understanding of the processes of change in this case and the therapeutic processes in general. In this good‐outcome case study, a team of raters integrated the temporal sequencing phase component of the Paradigmatic Complementarity Metamodel (PCM) with a moment‐by‐moment tracking method—the Developmental Analysis of Psychotherapy Process Method (DAPP)—to analyse what occurred along the process that could explain the phase transitions and consolida- tions observed and how the therapist facilitated them. We illustrate and explain the therapeutic progression with therapeutic interactions from the dyad. The results suggest that Lisa evolved in accordance with the sequence of phases proposed by the PCM until phase 4 (out of 7). However, only phase 2 gains show evidence of structural consolidation. The sequence of phases proposed by the PCM seems to represent a natural progression for patients throughout the therapeutic process, and the consideration of a phase‐by‐phase map in analysing and thinking of therapeutic cases may be a valuable tool regarding clinical decision making

Deep Eutectic Solvent aqueous solutions as efficient media for the solubilization of hardwood xylans

This work contributes to the development of integrated lignocellulosic-based biorefineries by the pioneering exploitation of hardwood xylans by solubilization and extraction in deep eutectic solvents (DES). DES formed by choline chloride and urea or acetic acid were initially evaluated as solvents for commercial xylan as a model compound. The effects of temperature, molar ratio, and concentration of the DES aqueous solutions were evaluated and optimized by using a response surface methodology. The results obtained demonstrated the potential of these solvents, with 328.23 g L-1 of xylan solubilization using 66.7 wt % DES in water at 80 °C. Furthermore, xylans could be recovered by precipitation from the DES aqueous media in yields above 90 %. The detailed characterization of the xylans recovered after solubilization in aqueous DES demonstrated that 4-O-methyl groups were eliminated from the 4-O-methylglucuronic acids moieties and uronic acids (15 %) were cleaved from the xylan backbone during this process. The similar Mw values of both pristine and recovered xylans confirmed the success of the reported procedure. DES recovery in four additional extraction cycles was also demonstrated. Finally, the successful extraction of xylans from Eucalyptus globulus wood by using aqueous solutions of DES was demonstrated.publishe

Case Series and DARS2 Variant Analysis in Early Severe Forms With Unexpected Presentations

Objective: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is regarded a relatively mild leukodystrophy, diagnosed by characteristic long tract abnormalities on MRI and biallelic variants in DARS2, encoding mitochondrial aspartyl-tRNA synthetase (mtAspRS). DARS2 variants in LBSL are almost invariably compound heterozygous; in 95% of cases, 1 is a leaky splice site variant in intron 2. A few severely affected patients, still fulfilling the MRI criteria, have been described. We noticed highly unusual MRI presentations in 15 cases diagnosed by WES. We examined these cases to determine whether they represent consistent novel LBSL phenotypes. Methods: We reviewed clinical features, MRI abnormalities, and gene variants and investigated the variants' impact on mtAspRS structure and mitochondrial function. Results: We found 2 MRI phenotypes: early severe cerebral hypoplasia/atrophy (9 patients, group 1) and white matter abnormalities without long tract involvement (6 patients, group 2). With antenatal onset, microcephaly, and arrested development, group 1 patients were most severely affected. DARS2 variants were severer than for classic LBSL and severer for group 1 than group 2. All missense variants hit mtAspRS regions involved in tRNAAsp binding, aspartyl-adenosine-5'-monophosphate binding, and/or homodimerization. Missense variants expressed in the yeast DARS2 ortholog showed severely affected mitochondrial function. Conclusions: DARS2 variants are associated with highly heterogeneous phenotypes. New MRI presentations are profound cerebral hypoplasia/atrophy and white matter abnormalities without long tract involvement. Our findings have implications for diagnosis and understanding disease mechanisms, pointing at dominant neuronal/axonal involvement in severe cases. In line with this conclusion, activation of biallelic DARS2 null alleles in conditional transgenic mice leads to massive neuronal apoptosis

Detection and characterization of subvisible aggregates of monoclonal lgG in serum

To detect and characterize the aggregation of therapeutic monoclonal antibodies in undiluted biological fluids. Fluorescently labeled subvisible IgG aggregates formed by applying either heat stress or by pH-shift were investigated immediately after addition to human serum, and after 24 h. Unstressed and stressed IgG formulations were analyzed by fluorescence single particle tracking, confocal laser scanning microscopy and flow cytometry. Unstressed formulations remained free from subvisible aggregates in serum, whereas heat-stressed and pH-shift stressed formulations showed dissimilar aggregation behaviors. The aggregation profile of the heat-stressed formulation diluted in serum remained practically the same as the one diluted in buffer, even after the 24 h incubation period. The pH-shift stressed formulation had strikingly smaller and more numerous subvisible aggregates immediately after dilution in serum compared to buffer. These aggregates became noticeably larger in both diluents after 24 h, but in serum they appeared to be formed by other types of constituents than the labeled protein itself. These results show that subvisible therapeutic protein aggregates may undergo changes in number, type and size distribution upon contact with human serum. This emphasizes the importance of analytical strategies for monitoring aggregation in undiluted biological fluids

Ibero-American Consensus on Low- and No-Calorie Sweeteners: Safety, Nutritional Aspects and Benefits in Food and Beverages

International scientific experts in food, nutrition, dietetics, endocrinology, physical activity, paediatrics, nursing, toxicology and public health met in Lisbon on 2-4 July 2017 to develop a Consensus on the use of low- and no-calorie sweeteners (LNCS) as substitutes for sugars and other caloric sweeteners. LNCS are food additives that are broadly used as sugar substitutes to sweeten foods and beverages with the addition of fewer or no calories. They are also used in medicines, health-care products, such as toothpaste, and food supplements. The goal of this Consensus was to provide a useful, evidence-based, point of reference to assist in efforts to reduce free sugars consumption in line with current international public health recommendations. Participating experts in the Lisbon Consensus analysed and evaluated the evidence in relation to the role of LNCS in food safety, their regulation and the nutritional and dietary aspects of their use in foods and beverages. The conclusions of this Consensus were: (1) LNCS are some of the most extensively evaluated dietary constituents, and their safety has been reviewed and confirmed by regulatory bodies globally including the World Health Organisation, the US Food and Drug Administration and the European Food Safety Authority; (2) Consumer education, which is based on the most robust scientific evidence and regulatory processes, on the use of products containing LNCS should be strengthened in a comprehensive and objective way; (3) The use of LNCS in weight reduction programmes that involve replacing caloric sweeteners with LNCS in the context of structured diet plans may favour sustainable weight reduction. Furthermore, their use in diabetes management programmes may contribute to a better glycaemic control in patients, albeit with modest results. LNCS also provide dental health benefits when used in place of free sugars; (4) It is proposed that foods and beverages with LNCS could be included in dietary guidelines as alternative options to products sweetened with free sugars; (5) Continued education of health professionals is required, since they are a key source of information on issues related to food and health for both the general population and patients. With this in mind, the publication of position statements and consensus documents in the academic literature are extremely desirable

Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19

Understanding dual career views of European university athletes: The more than gold project focus groups

Previous studies have found that student-athletes (S-As) have difficulties in achieving dual career (DC) success. However, no studies have analysed the opinion of the S-As on the functioning of DC with a qualitative methodology. The aim of the present work was to collect the opinions of elite university S-As in relation to DC policy adopted by their academic institutions in different European countries. In total, 77 athletes (F = 35, M = 42; age range: 20-25 years) participated in 15 national face-to-face focus groups in five different countries, to discuss aspects that higher education institutes should implement in relation to: 1) the athletes' needs; 2) assistance/tutorship: 2) curricula requirements; 3) financial support; 4) logistic support; 5) social support; and 6) dual career policies. Fifty of the athletes competed in individual sports and twenty-seven team sports. Of them, 57 was enrolled at undergraduate, 17 was enrolled in a master and 3 in a PhD. The athletes were presented with 13 open-ended questions one by one, and were ensured freedom to interact. All the discussions were recorded. After this, a general discussion took place in which the participants identified and agreed on a final list of statements from their focus group deemed to be relevant to DC athletes as university students. Then, at a consensus meeting, the findings were combined, repetitions were eliminated, and fragmented statements were condensed into broader ones. A final list of 31 statements, organized in six related content units, were identified in relation to the athletes' needs (n = 5), assistance/tutorship (n = 5), curricula requirements (n = 4), financial support (n = 4), logistic support (n = 4), social support (n = 6), and DC policies (n = 3), respectively. In conclusion, this cross-national qualitative research study synthesized the S-As views about their needs and the most relevant DC policies and provisions that higher education institutes should provide to ensure them with positive academic experiences towards the achievement of a degree

Use of green solvents as pre-treatment of dissolving pulp to decrease CS2 consumption from viscose production

Choline chloride-based deep eutectic solvents are widely used in biomass processing. In this work, four different green solvent mixtures were used as pre-treatment of acid sulphite dissolving pulp with the hypothesis of increasing the possibilities to produce viscose fibres and decreasing the use of the harmful and toxic carbon disulphide in the process. The experiments were performed at two different pulp to solvent mass ratios. Pulp quality parameters were also measured to determine the suitability of the pretreatment: a-cellulose, viscosity, lignin and pentosan content. In addition, X-ray diffraction analysis of pulps at the best solid to liquid ratio was performed to obtain the influence of the crystallinity index. Best results were obtained with the use of lactic acid, with reactivity values close to 94%, giving a reduction of CS2 usage of 15.83%. Furthermore, a linear relationship between the crystallinity index calculated by the XRD and reactivity with a regression factor of 0.87 was found