CULTURA DE LA CALIDAD, EVALUACIÓN Y ACREDITACIÓN

Objetivo: Analizar los desafíos que debe afrontar la universidad pública basada en la cultura de la evaluación con criterio autónomo para pasar a un criterio heterónomo, orientado a la validación nacional e internacional. Metodología: estudio descriptivo de tipo teórico Resultados: Se analizan las diversas concepciones de calidad y sus implicancias en las culturas universitarias tanto en lo referente al marco identitario, como a los mecanismos de evaluación y certificación. Conclusiones: El reto que se plantea a la educación superior, durante estas décadas ya no es el de la “crisis de expansión” sino más bien el de una “crisis de calidad” y por ende “la necesidad de evaluarse”. Ahora bien, sabido es que la calidad no es un concepto absoluto sino relativo, al igual que apreciación o evaluación. Cuando se utiliza el concepto cultura de evaluación, se alude a la capacidad institucional para llevar a cabo los procesos de autoevaluación y mejoramiento, en lugar de la simple práctica evaluativa, dirigida más al control que a la mejora. Dicho ésto el debate sobre qué entenderemos por calidad y los mecanismos que usemos para evaluarla, es central a la hora de definir el plan de mejora y reencauzar la gestión institucional

Immunomodulatory Agents with Antivascular Activity in the Treatment of Non-Small Cell Lung Cancer: Focus on TLR9 Agonists, IMiDs and NGR-TNF

Standard treatments for nonsmall cell lung cancer (NSCLC), such as surgery, chemotherapy, and radiotherapy, often lead to disappointing results. Unfortunately, also the various immunotherapeutic approaches so far tested have not produced satisfactory results to be widely applied in the clinical practice. However, the recent development of new immunomodulatory agents may open promising therapeutic options. This paper focuses on PF3512676, lenalidomide, and NGR-TNF, that is, drugs belonging to three different classes of immunomodulatory agents, that are also capable to affect tumor blood vessels with different mechanisms, and discusses the potential role of such agents in NSCLC treatment strategy

Evaluation of the applicability of sediment transport models to dam filling prediction in different Italian geological contexts

Artificial reservoirs are crucial infrastructures, since they allow for the management of the water resource they store and for their role in the hydroelectric production. Water is modulated and stored inside artificial basins built upstream of the dams for hydroelectric, industrial, drinking, irrigation, and flood mitigation purposes. However, as time passes, the deposition of solid material, transported by rivers flowing into the reservoir, reduces its storage capacity. In this work, a novel physicallybased erosion and sediment transport model developed by Politecnico di Milano (SMART-SED) is used to estimate dam filling in different Italian geological contexts. The present model differs from others in the literature since it can automatically detect drainage zones and it works at a basin scale, requiring few input parameters that can be easily downloaded from global or government databases. Moreover, it is based on robust and unconditionally stable numerical techniques, and it guarantees the mass conservation. The proposed model was applied to four watersheds, two in the Southern Alps and two in the Southern Apennines, with catchment areas ranging from 5 to 48 km2. After the model calibration on the local geological context, a validation of the obtained results was accomplished considering different time intervals and the available sediment filling data. It was observed that the SMART-SED model, initially developed for the evaluation of fluvial hazard and of sediment transport in mountainous areas, was also suitable for the estimation of dam filling. Results indeed show a precise approximation of the order of magnitude of the cumulative sediment volume produced inside the catchments and transported to the water basins. In the framework of a complex problem affecting the production of “clean” energy in a changing world, SMART-SED could become a useful tool also for dam management

Combined assessment of fluvial-marine sediment transport to determine the impact of coastal risks.

The study of morphological changes of a river channel, linked to erosion-deposition processes, taking place in the riverbed, is a topic of current interest in relation not only to the morphometric variations of the fluvial features (e.g., active channel width, area of sediment bars) and the sedimentary balance of the whole relative hydrographic basin but also in relation to the role of the sediment load transferred downstream up to the near shore area (Figure 1). These sediments constitute the solid transport that is pushed towards the coast and poured into the sea, representing a crucial sedimentary contribution to the beaches volumetric balance. The quantitative estimate of the volume of this fluvial load is currently achievable through robust approaches such as the morphological method grounded in the continuity principle applied to river sediments. To define the transport rates at selected locations (e.g., the river mouth) over a given time period, the method requires to measure the erosion and sedimentation volumes, which can be calculated using repeated Digital Elevation Models (DEM)and deriving a DEM of Difference (DoD) (Vericat et al., 2017; Capito et al., 2023). The coastal sedimentary balance is function of both the sediment load provided by rivers and the quantity of sediment transported by the longshore currents that move parallel to the coastline. For this reason, it is crucial to assess the impact of coastal erosion considering both the sediment input from the hydrographic basins and the longshore transport. Up to now there are no techniques capable of providing continuous and spatially distributed measurement of this sediment transfer, a fact of considerable interest if we think of the anthropic structures present along the shores, and the coast erosional problems. This study aims to evaluate, at the regional scale, the possibility of borrowing some techniques that are often used in fluvial contexts (e.g., geomorphological approach), to estimate the quantity of sediment that nourishes the coast. This information is essential as a preliminary step for further studies on the sediment transport process, considering, for instance, different climatic scenarios. A measured volume of sediments deposited over a specific time interval can be used to calibrate a physically-based sediment erosion and transport model, such as SMART-SED described by Gatti et al., 2023. Following calibration, the model can be employed to predict future scenarios by considering climate projections. An important aspect will be to assess the transferability of such methodologies taking into consideration the technical limitations (e.g., greater difficulty in acquiring bathymetric data in the submerged environment) and the morphodynamic differences of the two contexts (e.g., partial lack of lateral confinement of flows in the marine environment). Once it is established that meaningful estimates can be obtained, using the two solid transport estimates volumes (river and marine) it could be possible to obtain the budget of sediments that could benefit the near shore. This estimation certainly has a margin of error linked to all the uncertainties processes both in the river and coastal contexts, but it reveals an evaluation of sedimentary tendency of a coastal area: retreat, advancement or stationary. Today the studies of coastal balances certainly not considered the presence of submarine morphologies that favorthe sediments deposition (e.g., submerged bars and terraces) or the sediments removal (e.g., submarine canyons that arise very close to the coast) from near shore environment, significantly influencing the trend of longshore currents. In Italy there are many regions in which submarine canyons are very close to the coasts; these structures can act as collectors of sediments which are swallowed up towards greater depths (Lo Presti et al., 2022). Therefore, the quantitative study of sediment volume available on a near shore environment, linked to the presence of submarine morphologies favorable or not to the removal or stasis of sediments and to the intrinsic characteristic of the beach (e.g., long exposed beach, gulf, pocket beach), it constitutes a means of defining the sediment load that moves along a near shore area and which could influence and define possible scenarios of anthropic damage, as ports and fluvial bridges siltation but above coastal erosion risks

Polymer Identification and Specific Analysis (PISA) of Microplastic Total Mass in Sediments of the Protected Marine Area of the Meloria Shoals

Microplastics (MPs) quantification in benthic marine sediments is typically performed by time-consuming and moderately accurate mechanical separation and microscopy detection. In this paper, we describe the results of our innovative Polymer Identification and Specific Analysis (PISA) of microplastic total mass, previously tested on either less complex sandy beach sediment or less demanding (because of the high MPs content) wastewater treatment plant sludges, applied to the analysis of benthic sediments from a sublittoral area north-west of Leghorn (Tuscany, Italy). Samples were collected from two shallow sites characterized by coarse debris in a mixed seabed of Posidonia oceanica, and by a very fine silty-organogenic sediment, respectively. After sieving at <2 mm the sediment was sequentially extracted with selective organic solvents and the two polymer classes polystyrene (PS) and polyolefins (PE and PP) were quantified by pyrolysis-gas chromatography-mass spectrometry (Pyr-GC/MS). A contamination in the 8–65 ppm range by PS could be accurately detected. Acid hydrolysis on the extracted residue to achieve total depolymerization of all natural and synthetic polyamides, tagging of all aminated species in the hydrolysate with a fluorophore, and reversed-phase high performance liquid chromatography (HPLC) (RP-HPLC) analysis, allowed the quantification within the 137–1523 ppm range of the individual mass of contaminating nylon 6 and nylon 6,6, based on the detected amounts of the respective monomeric amines 6-aminohexanoic acid (AHA) and hexamethylenediamine (HMDA). Finally, alkaline hydrolysis of the residue from acid hydrolysis followed by RP-HPLC analysis of the purified hydrolysate showed contamination by polyethylene terephthalate (PET) in the 12.1–2.7 ppm range, based on the content of its comonomer, terephthalic acid

Association of immune-related adverse events with the outcomes of immune checkpoint inhibitors in patients with dMMR/MSI-H metastatic colorectal cancer

Neoplàsies gastrointestinals; Immunoteràpia; Biomarcadors tumoralsNeoplasias gastrointestinales; Inmunoterapia; Biomarcadores tumoralesGastrointestinal neoplasms; Immunotherapy; Tumor biomarkersBackground Immune checkpoint inhibitors (ICIs) show a tremendous activity in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), but a consistent fraction of patients does not respond. Prognostic/predictive markers are needed. Despite previous investigations in other tumor types, immune-related adverse events (irAEs) have not been well evaluated in patients with MSI-H cancers treated with ICIs. Methods We conducted an international cohort study at tertiary cancer centers collecting clinic-pathological features from 331 patients with MSI-H mCRC treated with ICIs. Of note, the irAEs were summarized using a ‘burden score’ constructed in a way that the same score value could be obtained by cumulating many low-grade irAEs or few high-grade irAEs; as a result, the lower the burden the better. Clearly, the irAE burden is not a baseline information, thus it was modeled as a time-dependent variable in univariable and multivariable Cox models. Results Among 331 patients, irAEs were reported in 144 (43.5%) patients. After a median follow-up time of 29.7 months, patients with higher burden of skin, endocrine and musculoskeletal irAEs (the latter two’s effect was confirmed at multivariable analysis) had longer overall survival (OS), as opposed to gastrointestinal, pneumonitis, neurological, liver, renal and other irAEs, which showed an harmful effect. Similar results were observed for progression-free survival (PFS). Based on the results retrieved from organ-specific irAEs, ‘aggregated’ burden scores were developed to distinguish ‘protective’ (endocrine and musculoskeletal) and ‘harmful’ (gastrointestinal, pneumonitis, neurological, hepatic) irAEs showing prognostic effects on OS and PFS. Conclusions Our results demonstrate that not all irAEs could exert a protective effect on oncologic outcome. An easy-to-use model for ICIs toxicity (burden score of protective and harmful irAEs) may be used as surrogate marker of response

The metabolic fingerprints of HCV and HBV infections studied by Nuclear Magnetic Resonance Spectroscopy

Abstract Few studies are available on metabolic changes in liver injuries and this is the first metabolomic study evaluating a group of HCV-positive patients, before and after viral eradication via DAA IFN-free regimens, using 1H-NMR to characterize and compare their serum fingerprints to naïve HBV-patients and healthy donors. The investigation clearly shows differences in the metabolomic profile of HCV patients before and after effective DAA treatment. Significant changes in metabolites levels in patients undergoing therapy suggest alterations in several metabolic pathways. It has been shown that 1H-NMR fingerprinting approach is an optimal technique in predicting the specific infection and the healthy status of studied subjects (Monte-Carlo cross validated accuracies: 86% in the HCV vs HBV model, 98.7% in the HCV vs HC model). Metabolite data collected support the hypothesis that the HCV virus induces glycolysis over oxidative phosphorylation in a similar manner to the Warburg effect in cancer, moreover our results have demonstrated a different action of the two viruses on cellular metabolism, corroborating the hypothesis that the metabolic perturbation on patients could be attributed to a direct role in viral infection. This metabolomic study has revealed some alteration in metabolites for the first time (2-oxoglutarate and 3-hydroxybutrate) concerning the HCV-infection model that could explain several extrahepatic manifestations associated with such an infection

Tyr78Phe Transthyretin Mutation with Predominant Motor Neuropathy as the Initial Presentation

Transthyretin (TTR) amyloidosis, the most frequent form of hereditary amyloidosis, is caused by dominant mutations in the TTR gene. More than 100 mutations have been identified. Clinical manifestations of TTR amyloidosis are usually induced by extracellular amyloid deposition in several organs. The major neurological manifestation is motor-sensory neuropathy associated with dysautonomic impairment. Here, we describe a 63-year-old man who came to our institution due to a suspected motor neuron disease. During a 4-year follow-up period, he underwent extensive clinical examination, electromyographic studies, sural nerve biopsy and TTR gene analysis by direct sequencing. Despite the predominant motor involvement, the detailed clinical examination also showed some mild sensory and dysautonomic signs. In addition, his clinical and family history included multiorgan disorders, such as carpal tunnel syndrome, as well as conditions with cardiac, renal, eye, and hepatic involvement. The sural nerve biopsy disclosed amyloid deposition, and the sequence analysis of the TTR gene detected a heterozygous Tyr78Phe substitution. The TTR gene variant found in our patient had only been described once so far, in a French man of Italian origin presenting with late-onset peripheral neuropathy and bilateral carpal tunnel syndrome. The predominant motor involvement presented by our patient is an uncommon occurrence and demonstrates the clinical heterogeneity of TTR amyloidosis

Glycogen storage disease type III: A novel Agl knockout mouse model

AbstractGlycogen storage disease type III is an autosomal recessive disease characterized by a deficiency in the glycogen debranching enzyme, encoded by AGL. Essential features of this disease are hepatomegaly, hypoglycemia, hyperlipidemia, and growth retardation. Progressive skeletal myopathy, neuropathy, and/or cardiomyopathy become prominent in adults. Currently, there is no available cure. We generated an Agl knockout mouse model by deletion of the carboxy terminus of the protein, including the carboxy end of the glucosidase domain and the glycogen-binding domain. Agl knockout mice presented serious hepatomegaly, but we did not observe signs of cirrhosis or adenomas. In affected tissues, glycogen storage was higher than in wild-type mice, even in the central nervous system which has never been tested in GSDIII patients. The biochemical findings were in accordance with histological data, which clearly documented tissue impairment due to glycogen accumulation. Indeed, electron microscopy revealed the disruption of contractile units due to glycogen infiltrations. Furthermore, adult Agl knockout animals appeared less prompt to move, and they exhibited kyphosis. Three-mo-old Agl knockout mice could not run, and adult mice showed exercise intolerance. In addition, older affected animals exhibited an accelerated respiratory rate even at basal conditions. This observation was correlated with severe glycogen accumulation in the diaphragm. Diffuse glycogen deposition was observed in the tongues of affected mice. Our results demonstrate that this Agl knockout mouse is a reliable model for human glycogenosis type III, as it recapitulates the essential phenotypic features of the disease