Liderazgo pedagógico directivo y la calidad de la gestión educativa de una IE rural- Tacna, 2022

El objetivo de la investigación fue: Determinar qué relación existe entre el Liderazgo pedagógico directivo y la calidad de la Gestión Educativa de una IE rural- Tacna, 2022, la investigación, corresponde al enfoque cuantitativo, del paradigma positivista, asimismo, el tipo de investigación es básica, de diseño no experimental, transversal, también asumen el nivel descriptivo correlacional. La muestra la conformó 17 docentes del nivel primario de una institución educativa rural, se aplicó dos encuestas validadas, por tres expertos, asimismo con niveles aceptables de confiabilidad, los resultados de la investigación según el nivel de significancia α (p<0.05), indica que existe una correlación positiva con una intensidad perfecta (r=0.925), entre el liderazgo pedagógico directivo con la calidad de la Gestión Educativa de una IE rural- Tacna, 2022

Double-zero degeneracy and heteroclinic cycles in a perturbation of the Lorenz system

In this paper we consider a 3D three-parameter unfolding close to the normal form of the triple-zero bifurcation exhibited by the Lorenz system. First we study analytically the double-zero degeneracy (a double-zero eigenvalue with geometric multiplicity two) and two Hopf bifurcations. We focus on the more complex case in which the double-zero degeneracy organizes several codimension-one singularities, namely transcritical, pitchfork, Hopf and heteroclinic bifurcations. The analysis of the normal form of a Hopf-transcritical bifurcation allows to obtain the expressions for the corresponding bifurcation curves. A degenerate double-zero bifurcation is also considered. The theoretical information obtained is very helpful to start a numerical study of the 3D system. Thus, the presence of degenerate heteroclinic and homoclinic orbits, T-point heteroclinic loops and chaotic attractors is detected. We find numerical evidence that, at least, four curves of codimension-two global bifurcations are related to the triple-zero degeneracy in the system analyzed.Ministerio de Economía y Competitividad MTM2017-87915-C2-1-PMinisterio de Ciencia, Innovación y Universidades - Fondos FEDER PGC2018-096265-B-I0Consejería de Economía, Innovación, Ciencia y Empleo - Junta de Andalucía FQM-276, TIC-0130, UHU-1260150 y P20_0116

Double-zero degeneracy and heteroclinic cycles in a perturbation of the Lorenz system

In this paper we consider a 3D three-parameter unfolding close to the normal form of the triple-zero bifurcation exhibited by the Lorenz system. First we study analytically the double-zero degeneracy (a double-zero eigenvalue with geometric multiplicity two) and two Hopf bifurcations. We focus on the more complex case in which the doublezero degeneracy organizes several codimension-one singularities, namely transcritical, pitchfork, Hopf and heteroclinic bifurcations. The analysis of the normal form of a Hopf-transcritical bifurcation allows to obtain the expressions for the corresponding bifurcation curves. A degenerate double-zero bifurcation is also considered. The theoretical information obtained is very helpful to start a numerical study of the 3D system. Thus, the presence of degenerate heteroclinic and homoclinic orbits, T-point heteroclinic loops and chaotic attractors is detected. We find numerical evidence that, at least, four curves of codimension-two global bifurcations are related to the triple-zero degeneracy in the system analyzed.We thank the reviewers for their careful reading of the manuscript and their very constructive remarks which have helped a lot to improve the presentation of the results. This work has been partially supported by the Ministerio de Economia y Competitividad, Spain (project MTM2017-87915-C2-1-P, co-financed with FEDER funds) , by the Ministerio de Ciencia, Innovacion y Universidades, Spain (project PGC2018-096265-B-I00, co-financed with FEDER funds) and by the Consejeria de Economia, Innovacion, Ciencia y Empleo de la Junta de Andalucia, Spain (FQM-276, TIC-0130, UHU-1260150 and P20_01160)

Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015–04 (PANGEA-Breast) study

Advanced breast cancer; Chemotherapy; PembrolizumabCáncer de mama avanzado; Quimioterapia; PembrolizumabCàncer de mama avançat; Quimioteràpia; PembrolizumabBackground We evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients. Methods HER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m2 [DL0]; 1,000 mg/m2 [DL1]) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed. Results Fourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon’s design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) ≥ 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5–32). Eight patients were treated ≥ 6 months before progression. Fourteen patients reported grade ≥ 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment. Conclusion Pembrolizumab 200 mg and gemcitabine 1,250 mg/m2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for ≥ 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit.The study was partially supported by a research grant from Merck (MSD in Europe) Investigator Initiated Studies Program, which also supplied pembrolizumab

Pembrolizumab Plus Gemcitabine in the Subset of Triple-Negative Advanced Breast Cancer Patients in the GEICAM/2015-04 (PANGEA-Breast) Study

Bomarkers; Breast cancer; PembrolizumabBiomarcadores; Cáncer de mama; PembrolizumabBiomarcadors; Càncer de mama; PembrolizumabThe PANGEA-Breast trial evaluated a new chemo-immunotherapeutic combination that would synergistically induce long-term clinical benefit in HER2-negative advanced breast cancer patients. Treatment consisted of 21-day cycles of 200 mg of pembrolizumab (day 1) plus gemcitabine (days 1 and 8). The primary objective was the objective response rate (ORR). The tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumor, and the myeloid-derived suppressor cells (MDSCs) level in peripheral blood, were analyzed to explore associations with treatment efficacy. Considering a two-stage Simon’s design, the study recruitment was stopped after its first stage as statistical assumptions were not met. A subset of 21 triple-negative breast cancer (TNBC) patients was enrolled. Their median age was 49 years; 15 patients had visceral involvement, and 16 had ≤3 metastatic locations. Treatment discontinuation due to progressive disease (PD) was reported in 16 patients. ORR was 15% (95% CI 3.2–37.9). Four patients were on treatment >6 months before PD. Grade ≥3 treatment-related adverse events were observed in 8 patients, where neutropenia was the most common. No association was found between TILs density, PD-L1 expression or MDSCs levels and treatment efficacy. ORR in TNBC patients also did not meet the assumptions, but 20% were on treatment >6 months.The study was partially supported by a research grant from Merck’s (MSD in Europe) Investigator Initiated Studies Program, which also supplied the pembrolizumab

Evaluación de la bioactividad de ciprofloxacino y vancomicina incorporados en cementos óseos poliacrílicos

La inclusión de antibióticos en el cemento óseo destinado a la fijación mecánica de las prótesis constituye un sistema de liberación local de antibiótico que permite minimizar la prevalencia y la gravedad de las reacciones adversas que pueden desencadenar los fármacos cuando éstos se administran por vía sistémica.El objetivo del trabajo es estudiar el mecanismo y cinética de liberación in vitro de ciprofloxacino y vancomicina incorporados en diferentes cementos óseos comerciales y evaluar la bioactividad mediante un ejercicio de simulación farmacocinética.Se prepararon mezclas de los cementos de estudio con ciprofloxacino clorhidrato y vancomicina (40:0,5:0,5). Los estudios de liberación se realizaron en agitación continua en solución salina de tampón fosfatos, pH=7,4, durante dos meses. Las cantidades liberadas acumuladas y las velocidades de elución se evaluaron mediante ANOVA. Con el fin estudiar la bioactividad, se realizó una simulación de Monte Carlo.La cantidad total liberada de ciprofloxacino en un periodo de 8 semanas fue de 0,29±0,06mg desde los cementos Palacos®, 0,44±0,06mg Lima® y 0,18±0,04mg Simplex®.La cantidad total de vancomicina liberada en 24 horas fue de 0,34±0,17mg desde el cemento Palacos®, 0,68±0,16mg Lima® y 0,17±0,02mg Simplex®. Transcurrido este tiempo la liberación cesó.El estudio de simulación, muestra que durante las primeras 72 horas, la cobertura antibiótica dependería tanto del cemento elegido, como de la sensibilidad del microorganismo y el día postquirúrgico. Teniendo en cuenta el drenaje externo, es de prever que tras estas primeras 72 horas, una vez retirado, la bioactividad aumente

Asistencia médica en festejos taurinos populares

Los festejos taurinos forman parte esencial de las tradiciones en las festividades de muchas de las localidades de Castilla y León. El papel de los equipos médicos es evidente dado el riesgo de lesiones potencialmente graves que pueden sufrirse y se encuentra regulado tanto por una normativa autonómica como estatal.Diferenciamos festejos populares, aquellos en los que participan aficionados no profesionales y festejos serios, en los que participan exclusivamente profesionales.Esta diferencia afecta a la legislación a aplicar y a los recursos asistenciales que deben movilizarse. Si bien la crisis económica de los últimos años puede hacer creer que se ha producido un descenso en el número de festejos, este descenso no es homogéneo y afecta preferentemente a los festejos serios, con una reducción del 30% mientras que apenas afecta a los populares.Las pautas asistenciales son las mismas que podemos aplicar a cualquier otro politraumátizado, basado en el ALTS. Las heridas por asta de toro presentan características especiales y la experiencia en este tipo de lesiones por parte de los miembros del equipo es fundamental. Se requieren equipos multidisciplinarios, bien formados, que se desplazan al lugar del festejo y cuya remuneración y reconocimiento no siempre son acordes con el trabajo realizado.The bullfights are an essential part of the traditions in several of the towns of Castilla y León. The role of the medical equipment is evident given the risk of potentially serious injuries that may be suffered and is regulated by both autonomic and state regulations.We differentiate the festivals, those in whichamateur are involved and serious festivities, which only professional involved. This difference affects the legislation to implement and health care resources to be mobilized. While the economic crisis of recent years may give the impression that there has been a decline in the number of celebrations, this decline is not homogeneous and preferentially affects the serious celebrations, with a reduction of 30% while only affects Popular.The guidelines are the same care that we can apply to any other politrauma injuries, basedin the ALTS atention. The bull horn wounds have special characteristics and experience in this type of injury by team members is essential.Shapely, multididciplinary teams traveling to the place of celebration and whose remuneration and recognition are not always commensurate with the work required

Regulation of neuronal energy metabolism by calcium: role of MCU and aralar/malate-aspartate shuttle

Calcium is a major regulator of cellular metabolism. Calcium controls mitochondrial respiration, and calcium signaling is used to meet cellular energetic demands through energy production in the organelle. Although it has been widely assumed that Ca2+-actions require its uptake by mitochondrial calcium uniporter (MCU), alternative pathways modulated by cytosolic Ca2+ have been recently proposed. Recent findings have indicated a role for cytosolic Ca2+ signals acting on mitochondrial NADH shuttles in the control of cellular metabolism in neurons using glucose as fuel. It has been demonstrated that AGC1/Aralar, the component of the malate/aspartate shuttle (MAS) regulated by cytosolic Ca2+, participates in the maintenance of basal respiration exerted through Ca2+-fluxes between ER and mitochondria, whereas mitochondrial Ca2+-uptake by MCU does not contribute. Aralar/MAS pathway, activated by small cytosolic Ca2+ signals, provides in fact substrates, redox equivalents and pyruvate, fueling respiration. Upon activation and increases in workload, neurons upregulate OxPhos, cytosolic pyruvate production and glycolysis, together with glucose uptake, in a Ca2+-dependent way, and part of this upregulation is via Ca2+ signaling. Both MCU and Aralar/MAS contribute to OxPhos upregulation, Aralar/MAS playing a major role, especially at small and submaximal workloads. Ca2+ activation of Aralar/MAS, by increasing cytosolic NAD+/NADH provides Ca2+-dependent increases in glycolysis and cytosolic pyruvate production priming respiration as a feed-forward mechanism in response to workload. Thus, except for glucose uptake, these processes are dependent on Aralar/MAS, whereas MCU is the relevant target for Ca2+ signaling when MAS is bypassed, by using pyruvate or β-hydroxybutyrate as substrate

Role of Isolated Limb Perfusion in the Era of Targeted Therapies and Immunotherapy in Melanoma. A Systematic Review of The Literature

Background. Isolated limb perfusion (ILP) is a locoregional procedure indicated by the unresectable melanoma of the limbs. Its complexity and highly demanding multidisciplinary approach means that it is a technique only implemented in a few referral centers around the globe. This report aims to examine its potential role in the era of targeted therapies and immunotherapy by conducting a systematic review of the literature on ILP. Methods. PubMed, Embase and Cochrane Library were searched. The eligibility criteria included publications from 2000–2020 providing valid data o effectiveness, survival or toxicity. Studies in which the perfusion methodology was not clearly described, letters to the editor, non-systematic reviews and studies that applied outdated clinical guidelines were excluded. To rule out studies of a low methodological quality and assess the risk of bias, the following aspects were also required: a detailed description of the applied ILP regimen, the clinical context, follow-up periods, analyzed clinical endpoints, and the number of analyzed ILPs. The disagreements were resolved by consensus. The results are presented in tables and figures. Results. Twenty-seven studies including 2637 ILPs were selected. The median overall response rate was 85%, with a median complete response rate of 58.5%. The median overall survival was 38 months, with a 5-year overall survival of 35%. The toxicity was generally mild according to Wieberdink toxicity criteria. Discussion. ILP still offer a high efficacy in selected patients. The main limitation of our review is the heterogeneity and age of most of the articles, as well as the absence of clinical trials comparing ILP with other procedures, making it difficult to transfer its results to the current era. Conclusions. ILP is still an effective and safe procedure for selected patients with unresectable melanoma of the limbs. In the era of targeted therapies and immunotherapy, ILP remains an acceptable and reasonable palliative treatment alternative, especially to avoid limb amputations. The ongoing clinical trials combining systemic therapies and ILP will provide more valuable information in the future to clarify the potential synergism of both strategies

Electromagnetic behavior of dielectric objects on metallic periodically nanostructured substrates

In this research, we investigate the electromagnetic behavior of a metallic thin-film with a periodic array of subwavelength apertures when dielectric objects are located on it. The influence of size, geometry and optical properties of the objects on the transmission spectra is numerically analyzed. We study the sensitivity of this system to changes in the refractive index of the illuminated volume induced by the presence of objects with sizes from hundreds of nanometers (submicron-sized objects) to a few microns (micron-sized objects). Parameters such as the object volume within the penetration depth of the surface plasmon in the buffer medium or the contact surface between the object and the nanostructured substrate strongly affect the sensitivity. The proposed system models the presence of objects and their detection through the spectral shifts undergone by the transmission spectra. Also, we demonstrate that these can be used for obtaining information about the refractive index of a micron-sized object immersed in a buffer and located on the nanostructured sensitive surface. We believe that results found in this study can help biomedical researchers and experimentalists in the process of detecting and monitoring biological organisms of large sizes (notably, cells).Ministerio de Economía y Competitividad (MINECO) (Secretaría de Estado de Investigación, Desarrollo e Innovación) (FIS2013-45854-P); Fundación IBERDROLA-ESPAÑA Research on Energy and the Environment Program. A.I.B. wants to thank the University of Cantabria for her FPU grant