Estudio técnico y propuesta de intervención del óleo sobre lienzo San José con el Niño Jesús (Ermita de la Consolación, Llutxent)

[ES] En el presente Trabajo de Fin de Grado se presenta el estudio técnico y la propuesta de intervención de un óleo sobre lienzo que se encuentra en la ermita de la Virgen de la Consolación de Llutxent (Valencia). La metodología de trabajo ha consistido en el estudio y vaciado documental sobre la iconografía de la obra; seguidamente se ha procedido al estudio de la pieza y la realización de fotografías para determinarla naturaleza de los materiales que la componen y su estado de conservación. Posteriormente se ha realizado un estudio de las patologías para elaborar la propuesta de intervención y conservación preventiva más adecuada a las necesidades de la obra.[EN] In the present Final Work Degree presents the technical study and the intervention proposal of an oil on canvas located in the chapel of the Virgen de la Consolación de Llutxent (Valencia). The work methodology has consisted of the study and the documentary emptying on the iconography of the work; then we have proceeded to the study of the piece and the realization of photographs to determine the nature of the materials that compose it and its state of conservation. Subsequently, a study of the pathologies was carried out in order to elaborate the most appropriate intervention and preventive conservation proposal according to the needs of the artwork.García Abad, C. (2021). Estudio técnico y propuesta de intervención del óleo sobre lienzo San José con el Niño Jesús (Ermita de la Consolación, Llutxent). Universitat Politècnica de València. http://hdl.handle.net/10251/172493TFG

Update on systemic treatment in early triple negative breast cancer

Triple negative breast cancer (TNBC) is a heterogeneous disease representing about 15% of all breast cancers. TNBC are usually high-grade histological tumors, and are generally more aggressive and difficult to treat due to the lack of targeted therapies available, and chemotherapy remains the standard treatment. There is a close relationship between pathological complete response after chemotherapy treatment and higher rates of disease-free survival and overall survival. In this review of systemic treatment in early triple negative breast cancer, our purpose is to analyze and compare different therapies, as well as to highlight the novelties of treatment in this breast cancer subtype.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors acknowledge grant CB16-12-00350 from CIBEROnc, the AMACMA foundation, and Lopez Trigo 2017.Medicin

Compelling DNA intercalation through ‘anion– anion’ anti-coulombic interactions: boron cluster self-vehicles as promising anticancer agents

Anticancer drugs inhibit DNA replication by intercalating between DNA base pairs, forming covalent bonds with nucleotide bases, or binding to the DNA groove. To develop safer drugs, novel molecular structures with alternative binding mechanisms are essential. Stable boron hydrides offer a promising alternative for cancer therapy, opening up additional options like boron neutron capture therapy based on 10B and thermal neutron beams or proton boron fusion therapy using 11B and proton beams. These therapies are more efficient when the boron compound is ideally located inside cancer cells, particularly in the nucleus. Current cancer treatments often utilize small, polycyclic, aromatic, planar molecules that intercalate between ds-DNA base pairs, requiring only a spacing of approximately 0.34 nm. In this paper, we demonstrate another type of intercalation. Notably, [3,3′-Fe(1,2-C2B9H11)2]−, ([o-FESAN]−), a compact 3D molecule measuring 1.1 nm × 0.6 nm, can as well intercalate by strong non-bonding interactions preferentially with guanine. Unlike known intercalators, which are positive or neutral, [o-FESAN]− is a negative species and when an [o-FESAN]− molecule approaches the negatively charged DNA phosphate chain an anion–anion interaction consistently anti-electrostatic via Ccluster–H⋯O–P bonds occurs. Then, when more molecules approach, an elongated outstandingly self-assembled structure of [o-FESAN]−–[o-FESAN]− forms moving anions towards the interthread region to interact with base pairs and form aggregates of four [o-FESAN]− anions per base pair. These aggregates, in this environment, are generated by Ccluster–H⋯O–C, N–H⋯H–B and Ccluster–H⋯H–B interactions. The ferrabis(dicarbollide) boron-rich small molecules not only effectively penetrate the nucleus but also intercalate with ds-DNA, making them promising for cancer treatment. This amphiphilic anionic molecule, used as a carrier-free drug, can enhance radiotherapy in a multimodal perspective, providing healthcare professionals with improved tools for cancer treatment. This work demonstrates these findings with a plethora of techniquesAuthors received support from the Spanish Ministerio de Economía y Competitividad (PID2020-116728RB-I00, PID2022-136802NB-I00, RED2022-134120-T and TED2021-129738B-I00), the Generalitat de Catalunya (2017SGR1720). L. Gutiérrez Gálvez was supported by FPU19/06309 grant from the Spanish Ministry of Universities. S. Y. was supported by the China Scholarship Council (CSC) under Grant No. 202006990034

Treatment decision-making in chronic lymphocytic leukaemia: Key factors for healthcare professionals. PRELIC study

Objective: To explore the preferences of Spanish healthcare professionals (haematologists and hospital pharmacists) for the treatment selection of active Chronic Lymphocytic Leukaemia (CLL) patients at first relapse, condition that mainly afflicts older adults. Methods: A discrete choice experiment (DCE) was conducted among haematologists and hospital pharmacists. A literature review and a focus group informed the DCE design. CLL treatment settings were defined by seven attributes: four patient/disease-related attributes (age, functional status, comorbidities, and risk of the disease) and three treatment-related attributes (efficacy [hazard ratio of progression-free survival, HR-PFS], rate of discontinuations due to adverse events and cost). A mixed-logit model was used to determine choice-based preferences. Relative importance (RI) of attributes was calculated and compared between stakeholders. Willingnessto-pay (WTP) was estimated through the DCE. Besides, nine ad-hoc questions were posed, to explore more in depth CLL treatment decision making. Results: A total of 130 participants (72 haematologists and 58 hospital pharmacists) answered the DCE. All attributes were significant predictors of preferences (p b 0.05) in the multinomial model. Higher RI was obtained for treatment-related attributes: the highest rated being ‘cost’ (23.8%) followed by ‘efficacy’ (20.9%). Regarding patient-related attributes, the highest RI was obtained for ‘age’ (18.1%). No significant differences (p N 0.05) in RI between haematologists and pharmacists were found. WTP for the treatment was higher for younger CLL patients. Ad-hoc questions showed that patient age and functional status influence treatment decisions. Conclusions: For healthcare professionals, ‘cost’ and ‘efficacy’ (treatment-related attributes) and age (patientrelated attribute) are the m

Aplicación de la metodología Aprendizaje - Servicio a alumnos que cursan el Máster en Economía Internacional y Desarrollo

Depto. de Economía Aplicada, Estructura e HistoriaFac. de Ciencias Económicas y EmpresarialesFALSEsubmitte

Characterization of mutant versions of the R-RAS2/TC21 GTPase found in tumors

The R-RAS2 GTP hydrolase (GTPase) (also known as TC21) has been traditionally considered quite similar to classical RAS proteins at the regulatory and signaling levels. Recently, a long-tail hotspot mutation targeting the R-RAS2/TC21 Gln72 residue (Q72L) was identified as a potent oncogenic driver. Additional point mutations were also found in other tumors at low frequencies. Despite this, little information is available regarding the transforming role of these mutant versions and their relevance for the tumorigenic properties of already-transformed cancer cells. Here, we report that many of the RRAS2 mutations found in human cancers are highly transforming when expressed in immortalized cell lines. Moreover, the expression of endogenous R-RAS2Q72L is important for maintaining optimal levels of PI3K and ERK activities as well as for the adhesion, invasiveness, proliferation, and mitochondrial respiration of ovarian and breast cancer cell lines. Endogenous R-RAS2Q72L also regulates gene expression programs linked to both cell adhesion and inflammatory/immune-related responses. Endogenous R-RAS2Q72L is also quite relevant for the in vivo tumorigenic activity of these cells. This dependency is observed even though these cancer cell lines bear concurrent gain-of-function mutations in genes encoding RAS signaling elements. Finally, we show that endogenous R-RAS2, unlike the case of classical RAS proteins, specifically localizes in focal adhesions. Collectively, these results indicate that gain-of-function mutations of R-RAS2/TC21 play roles in tumor initiation and maintenance that are not fully redundant with those regulated by classical RAS oncoproteins

A hotspot mutation targeting the R-RAS2 GTPase acts as a potent oncogenic driver in a wide spectrum of tumors

A missense change in RRAS2 (Gln to Leu), analogous to the Gln-to-Leu mutation of RAS oncoproteins, has been identified as a long-tail hotspot mutation in cancer and Noonan syndrome. However, the relevance of this mutation for in vivo tumorigenesis remains understudied. Here we show, using an inducible knockin mouse model, that R-Ras2 triggers rapid development of a wide spectrum of tumors when somatically expressed in adult tissues. These tumors show limited overlap with those originated by classical Ras oncogenes. R-Ras2-driven tumors can be classified into different subtypes according to therapeutic susceptibility. Importantly, the most relevant R-Ras2-driven tumors are dependent on mTORC1 but independent of phosphatidylinositol 3-kinase-, MEK-, and Ral guanosine diphosphate (GDP) dissociation stimulator. This pharmacological vulnerability is due to the extensive rewiring by R-Ras2 of pathways that orthogonally stimulate mTORC1 signaling. These findings demonstrate that RRAS2 is a bona fide oncogenic driver and unveil therapeutic strategies for patients with cancer and Noonan syndrome bearing RRAS2 mutations.We thank M. Blázquez and the personnel of the CIC Flow Cytometry, Microscopy, Pathology, and Genomics Units for expert technical work. X.R.B.’s project leading to these results has received funding from the Spanish Association against Cancer (GC16173472GARC), the Castilla-León government (CSI252P18, CSI145P20, and CLC-2017-01), the RTI2018-096481-B-100 grant cofounded by MCIN/AEI/10.13039/501100011033 and the European Research Development Fund “A way of making Europe” of the European Union, and “la Caixa” Banking Foundation (HR20-00164). X.R.B.’s institution is supported by the Programa de Apoyo a Planes Estratégicos de Investigación de Estructuras de Investigación de Excelencia of the Castilla-León government (CLC-2017-01). J.R.-V. received funding from the Carlos III Health Institute (PI20/01724). J.R.-V.’s contract is supported by a senior postdoctoral contract of the Spanish Association against Cancer. L.C.’s contract was supported by contracts from the Spanish Association against Cancer and the CLC-2017-01 grant. L.F.L.-M.’s contract was mostly supported by funding from the Spanish Ministry of Education, Culture and Sports (FPU13/02923) and, subsequently, by the CLC-2017-01 grant. R.C. was supported by a predoctoral contract from the MSI (BES-2016-0077909) and the CLC-2017-01 grant

Combination of Tocilizumab and Steroids to Improve Mortality in Patients with Severe COVID-19 Infection : A Spanish, Multicenter, Cohort Study

We aimed to determine the impact of tocilizumab use on severe COVID-19 (coronavirus disease 19) pneumonia mortality. We performed a multicentre retrospective cohort study in 18 tertiary hospitals in Spain from March to April 2020. Consecutive patients admitted with severe COVID-19 treated with tocilizumab were compared to patients not treated with tocilizumab, adjusting by inverse probability of the treatment weights (IPTW). Tocilizumab's effect in patients receiving steroids during the 48 h following inclusion was analysed. During the study period, 506 patients with severe COVID-19 fulfilled the inclusion criteria. Among them, 268 were treated with tocilizumab and 238 patients were not. Median time to tocilizumab treatment from onset of symptoms was 11 days [interquartile range (IQR) 8-14]. Global mortality was 23.7%. Mortality was lower in patients treated with tocilizumab than in controls: 16.8% versus 31.5%, hazard ratio (HR) 0.514 [95% confidence interval (95% CI) 0.355-0.744], p < 0.001; weighted HR 0.741 (95% CI 0.619-0.887), p = 0.001. Tocilizumab treatment reduced mortality by 14.7% relative to no tocilizumab treatment [relative risk reduction (RRR) 46.7%]. We calculated a number necessary to treat of 7. Among patients treated with steroids, mortality was lower in those treated with tocilizumab than in those treated with steroids alone [10.9% versus 40.2%, HR 0.511 (95% CI 0.352-0.741), p = 0.036; weighted HR 0.6 (95% CI 0.449-0.804), p < 0.001] (interaction p = 0.094). These results show that survival of patients with severe COVID-19 is higher in those treated with tocilizumab than in those not treated and that tocilizumab's effect adds to that of steroids administered to non-intubated patients with COVID-19 during the first 48 h of presenting with respiratory failure despite oxygen therapy. Randomised controlled studies are needed to confirm these results. European Union electronic Register of Post-Authorization Studies (EU PAS Register) identifier, EUPAS34415 The online version of this article (10.1007/s40121-020-00373-8) contains supplementary material, which is available to authorized users

Urgent urinary diversion by intrinsic or extrinsic obstructive disease of the urinary tract. Percutaneous nephrostomy versus ureteral stent

Introducción: La obstrucción de la vía urinaria es una patología urgente que se presenta con relativa frecuencia y que en determinados casos requiere de derivación urinaria inminente. El objetivo de este estudio es analizar los resultados y complicaciones en pacientes con obstrucción de la vía urinaria superior tras derivación urinaria con stent ureteral versus nefrostomía percutánea. Métodos: Estudio retrospectivo desde 1 Enero de 2011 a 31 Diciembre de 2012 incluyendo 134 pacientes (65 hombres, 69 mujeres) de edad media 61.2 ± 17.4 años procedentes de Urgencias y requirieron derivación urinaria urgente. Se analiza según el tipo de derivación urinaria diferentes parámetros etiológicos, estancia hospitalaria, evolución clínica y analítica y complicaciones. Resultados: De los 134 pacientes, en 89 casos se optó por colocación de stent ureteral y en 45 casos de nefrostomía percutánea. Los pacientes en los que se colocó nefrostomía percutánea eran más añosos y presentaban unos niveles más elevados de creatinina respecto al grupo de stent ureteral de forma significativa. No se encontraron diferencias estadísticamente significativas en la evolución clínica o analítica entre una u otra derivación, únicamente en la estancia hospitalaria que fue mayor para los pacientes con nefrostomía debido a la mayor edad, mayores cifras de creatinina al ingreso y mayor comorbilidad. Conclusión: No existen diferencias en los resultados y complicaciones entre stent ureteral y nefrostomía, si bien consideramos el stent ureteral como primera opción ante una obstrucción aguda de la vía, reservando la nefrostomía para casos de obstrucción maligna, sepsis con alteración de parámetros inflamatorios y mayor comorbilidad.Introduction: Obstruction of the urinary tract is a relatively frequent disease and sometimes requires urgent urinary derivation. The objective of this study was to compare outcomes and complications in patients with upper urinary tract obstruction after urinary derivation with ureteral stent or percutaneous nephrostomy. Material and Methods: A retrospective study was conducted from 1 January 2011 to 31 December 2012 in 134 patients (65 males, 69 females) with a mean age of 61.2 ± 17.4 yrs who came to our emergency department requiring urgent urinary derivation. Data were gathered on the type of urinary derivation, aetiology, length of hospital stay, clinical and analytical results and complications. Results: A ureteral stent was placed in 89 of the 134 patients and percutaneous nephrostomy in the remaining 45. Creatinine levels and age were significantly higher in the percutaneous nephrostomy versus ureteral stent group. No inter-group differences were found in clinical or analytical outcomes. The hospital stay was longer for the percutaneous nephrostomy patients, attributable to their higher mean age, admission creatinine level, and comorbidities. Conclusions: No differences in outcomes or complications were found between ureteral stent and percutaneous nephrostomy placement. Ureteral stents may be preferable in patients with acute tract obstruction and nephrostomy preferable in patients with malignant obstruction or sepsis with altered inflammatory parameters and a greater comorbidity burden

1° Jornadas en Derecho, Justicia y Sociedad. Críticas y desafíos a 40 años de democracia

Fil: Copetti, Agostina. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Copetti, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Gaiteri, Esmeralda. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Gaiteri, Esmeralda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Pezzano, Sofía. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Pezzano, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Tassin Wallace, Catalina. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Tassin Wallace, Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Abad, Natanael Yamil. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Abad, Natanael Yamil. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: García Garro, Rocío. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: García Garro, Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Manzo, Alejandro Gabriel. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Manzo, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Moreno, Patricia Giuliana. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Moreno, Patricia Giuliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Sabattini, Nicolás Jesús. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Sabattini, Nicolás Jesús. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Villordo Paz, Paula Magalí. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Villordo Paz, Paula Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Caccia, Ana Clara. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Caccia, Ana Clara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Ávila Castro, Maria Paula. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Ávila Castro, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Reinoso, Paula. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Reinoso, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Deangeli, Melina Andrea. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Deangeli, Melina Andrea.Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Caravaca, Mariana Celeste. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Caravaca, Mariana Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Mousist, Victoria Inés. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Mousist, Victoria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Quinteros, Cristian. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Quinteros, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.En el presente volumen se reúnen algunas de las ponencias que se expusieron en las “I Jornadas en Derecho, Justicia y Sociedad. Críticas y desafíos a 40 años de democracia”, organizadas por el Instituto de Estudios sobre Derecho, Justicia y Sociedad (CONICET - UNC). Esta primera edición de las Jornadas se llevó a cabo los días 9 y 10 de noviembre del año 2023, en la sede del Instituto de Estudios sobre Derecho, Justicia y Sociedad (CONICET - UNC). Con motivo de la conmemoración de los 40 años ininterrumpidos de democracia en nuestro país, las jornadas tuvieron el objetivo principal de generar un espacio para reflexionar sobre la ciencia jurídica y el derecho en su interacción con otros campos disciplinares. La discusión se desarrolló en 15 mesas temáticas, con más de 70 ponentxs en total, en las que se dio un intercambio entre docentes, estudiantes, investigadorxs y miembros de organizaciones sociales provenientes de distintas disciplinas. En este marco y ante tan amplia convocatoria, se abrió la posibilidad de promover perspectivas críticas y novedosas.info:eu-repo/semantics/publishedVersionFil: Copetti, Agostina. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Copetti, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Gaiteri, Esmeralda. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Gaiteri, Esmeralda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Pezzano, Sofía. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Pezzano, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Tassin Wallace, Catalina. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Tassin Wallace, Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Abad, Natanael Yamil. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Abad, Natanael Yamil. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: García Garro, Rocío. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: García Garro, Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Manzo, Alejandro Gabriel. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Manzo, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Moreno, Patricia Giuliana. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Moreno, Patricia Giuliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Sabattini, Nicolás Jesús. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Sabattini, Nicolás Jesús. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Villordo Paz, Paula Magalí. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Villordo Paz, Paula Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Caccia, Ana Clara. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Caccia, Ana Clara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Ávila Castro, Maria Paula. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Ávila Castro, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Reinoso, Paula. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Reinoso, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Deangeli, Melina Andrea. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Deangeli, Melina Andrea.Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Caravaca, Mariana Celeste. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Caravaca, Mariana Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Mousist, Victoria Inés. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Mousist, Victoria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Quinteros, Cristian. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Quinteros, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina