29 research outputs found
Multivariate Gram-Charlier Densities
Get PDFThis paper introduces a new family of multivariate distributions based on Gram-Charlier and Edgeworth expansions. This family encompasses many of the univariate seminonparametric densities proposed in the financial econometrics as marginal distributions of the different formulations. Within this family, we focus on the specifications that guarantee positivity so obtaining a well-defined multivariate density. We compare different "positive" multivariate distributions of the family with the multivariate Edgeworth-Sargan, Normal and Student’s t in an in- and out-sample framework for financial returns data. Our results show that the proposed specifications provide a quite reasonably good performance being so of interest for applications involving the modelling and forecasting of heavy-tailed distributions.Multivariate distributions; Gram-Charlier and Edgeworth-Sargan densities; MGARCH models; financial data
Global economy dynamics? Panel data approach to spillover effects
Get PDFOver the past year, there has been considerable debate about how the slowing of the United States and other major developed economies affects output growth across the world. The main purpose of this paper is to establish relevant conclusions on how the U.S., Euro Area and Japan gross domestic product growth affect international business cycle fluctuations, with the objective of identifying the main factors that influence spillovers into other countries. Using panel data regression, we conclude that output growth in the U.S. and Euro area are significant in explaining output growth across countries. Depending on the specifications, trade linkages play a significant role while financial linkages with respect to the three regions does not (except in one particular specification). There are signs of potential omitted variable bias in some regression indicating that some relevant variables have not been taken into account. There is also clear evidence of a structural change in the transmission mechanism of shocks after 1985 – since when shocks have become more country-specific.Output Growth, Trade and Financial Linkages, Structural Break, Cross- Section Panel Data.
Uncontrolled donation programs after out-of-hospital cardiac arrest. An estimation of potential donors
No full textTo determine the number of potential deceased organ donors from out-of- hospital cardiac arrest cases (OHCA) attended by public physician-led emergency medical services in Spain, based on data recorded in the nationwide Spanish OHCA Registry (OHSCAR). We analysed OHSCAR data on deceased OHCA patients in Spain during 13 months (1/10/2013 to 31/10/2014). Variables included age, sex, estimated OHCA time, cardiopulmonary resuscitation (CPR) start time and outcome. Inclusion criteria were: age 16-60 years, witnessed OHCA, no return of spontaneous circulation (ROSC) and time interval Of a total 8789 cases, 3290 met the age criteria; of these, CPR was not witnessed in 745 cases. Among the remaining 2545 patients, 141 were included in uncontrolled donation after cardiac death (uDCD) programs, 902 arrived at the hospital with ROSC, 64 arrived with ongoing CPR and 15 cases were lost to follow-up. Of the remaining 1423 without ROSC, CPR initiation time was not recorded in 454 cases and 398 did not meet the time criteria Many potential donors are missed in current clinical practice. uDCD programs are few and underused even in a country with high rates of organ transplantation
Herramienta Digital Como Estrategia Para el Proceso de Enseñanza del Concepto de Funciones Trigonométricas del Grado Décimo del Colegio José María Landázuri Landázuri (Santander)
No full textDigitalLa propuesta de investigación tiene como objetivo mejorar el rendimiento académico en
el área de matemáticas con la temática relacionada a funciones trigonométricas, empleando la
herramienta digital de GeoGebra e implementando clases didácticas con dicho simulador, para
los estudiantes de décimo grado del Colegio José María Landázuri.
El método de investigación utilizado incluye el análisis cuantitativo. Se busca entonces,
mediante una propuesta de intervención didáctica favorecer a los estudiantes de decimo, sobre
los conceptos, características y propiedades de las funciones trigonométricas. Para ello se
tomaron algunos elementos pertinentes desde la caracterización, diseño e implementación
didáctica para explicar algunos de los fenómenos que ocurren con las funciones
trigonométricas.
En la ejecución de la propuesta de intervención didáctica se usó el simulador de
GeoGebra como herramienta mediadora en el aprendizaje de los conceptos trabajados.
La población está compuesta por dos grupos de estudiantes, el grupo de base con 33
estudiantes y el grupo experimental también con la misma cantidad de estudiantes, del área
urbana y rural por las condiciones locales. En la fase inicial se realizó una prueba diagnóstica
(conocimientos previos) y luego se implementó el diseño de clases didácticas para promover la
visualización en la enseñanza de las funciones trigonométricas con ayuda de la herramienta
digital. Finalmente, se volvió a realizar una prueba final o posprueba, dando como resultado la
viabilidad de la propuesta de intervención didáctica.The research proposal aims to improve academic performance in the area of
mathematics with the subject related to trigonometric functions, using the GeoGebra digital tool
and implementing didactic classes with said simulator, for the tenth grade students of the José
María Landázuri School.
The research method used includes quantitative analysis. It is then sought, through a
didactic intervention proposal, to favor tenth-grade students on the concepts, characteristics and
properties of trigonometric functions. For this, some pertinent elements were taken from the
characterization, design and didactic implementation to explain some of the phenomena that
occur with the trigonometric functions.
In the execution of the didactic intervention proposal, the GeoGebra simulator was used
as a mediating tool in the learning of the concepts worked on.
The population is composed of two groups of students, the base group with 33 students
and the experimental group also with the same number of students, from urban and rural areas
due to local conditions. In the initial phase, a diagnostic test (prior knowledge) was carried out
and then the design of didactic classes was implemented to promote visualization in the
teaching of trigonometric functions with the help of the digital tool.
Finally, a final test or post-test was carried out again, resulting in the viability of the
didactic intervention proposal.Capítulo 1. Presentación del trabajo de grado ........................................................................... 20
1.1.Planteamiento del problema.................................................................................................. 20
1.1.1.Descripción de la situación problema................................................................................. 20
1.1.2.Identificación del problema................................................................................................. 21
1.1.3.Pregunta problema............................................................................................................. 23
1.2.Justificación........................................................................................................................... 23
1.3.Objetivos ............................................................................................................................... 25
1.3.1.Objetivo general ................................................................................................................ 25
1.3.2.Objetivos específicos ......................................................................................................... 25
Capítulo 2. Bases teóricas ......................................................................................................... 26
2.1. Aportes al Estado del Arte.................................................................................................... 26
2.2. Marco Teórico ...................................................................................................................... 28
2.3. Marco Conceptual ............................................................................................................... 33
•Matemáticas ....................................................................................................... 33
•Dimensiones cognitivas............................................................................................................. 34
•TIC............. 35
•Teorías de aprendizaje y su relación con las TICs.................................................................... 36
•Las TICs en la educación .......................................................................................................... 37
Capítulo 3. Diseño Metodológico ............................................................................................... 42
3.1. Tipo de Investigación .......................................................................................................... 42
3.1.1. Etapas del diseño cuasi-experimental.............................................................................. 44
3.2. Alcance 45
3.2.1. Hipótesis de investigación:................................................................................................ 45
3.2.2. Hipótesis nula: 46
3.2.3. Variables 46
3.2.4. Validez 46
3.3. Operacionalización de Variables.......................................................................................... 46
3.4. Población, Participantes y Selección de la muestra............................................................. 49
3.4.1 Fases De La Investigación................................................................................................. 49
3.4.2. Instrumentos de recolección de datos............................................................................... 49
3.4.3. Temáticas Posibles ........................................................................................................... 50
3.4.4. Técnicas de análisis de datos ........................................................................................... 51
Capítulo 4. Consideraciones Éticas ........................................................................................... 52
Capítulo 5. Diagnóstico .............................................................................................................. 53
5.1. Aplicación de Prueba Diagnóstica........................................................................................ 54
Capítulo 6. Estructura de la Propuesta de Intervención............................................................. 61
6.1. Propuesta Pedagógica........................................................................................................ 61
6.2. Desarrollo de la Metodología. .............................................................................................. 63
6.2.1. Actividad uno: utilización de softwares.............................................................................. 63
6.2.2. Sistema de representación............................................................................................... 64
6.2.3. Actividad dos: Fenomenología del tema y modelización .................................................. 65
6.2.4. Actividad tres: Recursos y material didáctico.................................................................... 68
6.4. Componente Tecnológico ................................................................................................... 70
6.5. Implementación.................................................................................................................... 74
6.5.1. Fase 1- Caracterización ................................................................................................... 74
6.5.2. Fase 2: Diseño 75
6.5.3 Fase 3: Implementación de la Posprueba........................................................................ 111
Capítulo 7. Aanálisis e interpretación de datos ........................................................................ 113
Capítulo 8. Conclusiones ......................................................................................................... 144
Capítulo 9. Limitaciones ........................................................................................................... 147
Capítulo 10. Impacto, recomendaciones y trabajos futuros ..................................................... 148
10.1. Impacto............................................................................................................................. 148
10.2. Recomendaciones y Trabajos Futuros............................................................................. 149
Referencias .............................................................................................................................. 151
Apéndices................................................................................................................................. 158MaestríaMagíster en Tecnologías Digitales Aplicadas a la Educación1°e
Intratumoral BO-112 in combination with radiotherapy synergizes to achieve CD8 T-cell-mediated local tumor control
No full textBACKGROUND: Radioimmunotherapy combines irradiation of tumor lesions with immunotherapy to achieve local and abscopal control of cancer. Most immunotherapy agents are given systemically, but strategies for delivering immunotherapy locally are under clinical scrutiny to maximize efficacy and avoid toxicity. Local immunotherapy, by injecting various pathogen-associated molecular patterns, has shown efficacy both preclinically and clinically. BO-112 is a viral mimetic based on nanoplexed double-stranded RNA (poly I:C) which exerts immune-mediated antitumor effects in mice and humans on intratumoral delivery. BO-112 and focal irradiation were used to make the proof-of-concept for local immunotherapy plus radiation therapy combinations. METHODS: Murine transplantable tumor cell lines (TS/A, MC38 and B16-OVA) were used to show increased immunogenic features under irradiation, as well as in bilateral tumor models in which only one of the lesions was irradiated or/and injected with BO-112. Flow cytometry and multiplex tissue immunofluorescence were used to determine the effects on antitumor immunity. Depletions of immune cell populations and knockout mice for the IFNAR and BATF-3 genes were used to delineate the immune system requirements for efficacy. RESULTS: In cultures of TS/A breast cancer cells, the combination of irradiation and BO-112 showed more prominent features of immunogenic tumor cell death in terms of calreticulin exposure. Injection of BO-112 into the tumor lesion receiving radiation achieved excellent control of the treated tumor and modest delays in contralateral tumor progression. Local effects were associated with more prominent infiltrates of antitumor cytotoxic tumor lymphocytes (CTLs). Importantly, local irradiation plus BO-112 in one of the tumor lesions that enhanced the therapeutic effects of radiotherapy on distant irradiated lesions that were not injected with BO-112. Hence, this beneficial effect of local irradiation plus BO-112 on a tumor lesion enhanced the therapeutic response to radiotherapy on distant non-injected lesions. CONCLUSION: This study demonstrates that local BO-112 immunotherapy and focal irradiation may act in synergy to achieve local tumor control. Irradiation plus BO-112 in one of the tumor lesions enhanced the therapeutic effects on distant irradiated lesions that were not injected with BO-112, suggesting strategies to treat oligometastatic patients with lesions susceptible to radiotherapy and with at least one tumor accessible for repeated BO-112 intratumoral injections
A protective personal factor against disability and dependence in the elderly: an ordinal regression analysis with nine geographically-defined samples from Spain
No full textBackground: Sense of Coherence (SOC) is defined as a tendency to perceive life experiences as comprehensible, manageable and meaningful. The construct is split in three major domains: Comprehensibility, Manageability, and Meaningfulness. SOC has been associated with successful coping strategies in the face of illness and traumatic events and is a predictor of self-reported and objective health in a variety of contexts. In the present study we aim to evaluate the association of SOC with disability and dependence in Spanish elders. Methods: A total of 377 participants aged 75 years or over from nine locations across Spain participated in the study (Mean age: 80.9 years; 65.3% women). SOC levels were considered independent variables in two ordinal logistic models on disability and dependence, respectively. Disability was established with the World health Organization-Disability Assessment Schedule 2.0 (36-item version), while dependence was measured with the Extended Katz Index on personal and instrumental activities of daily living. The models included personal (sex, age, social contacts, availability of an intimate confidant), environmental (municipality size, access to social resources) and health-related covariates (morbidity). Results: High Meaningfulness was a strong protective factor against both disability (Odds Ratio [OR] = 0.50; 95% Confidence Interval [CI] = 0.29-0.87) and dependence (OR = 0.33; 95% CI = 0.19-0.58) while moderate and high Comprehensibility was protective for disability (OR = 0.40; 95% CI = 0.22-0.70 and OR = 0.39; 95% CI = 0.21-0.74), but not for dependence. Easy access to social and health resources was also highly protective against both disability and dependence. Conclusions: Our results are consistent with the view that high levels of SOC are protective against disability and dependence in the elderly. Elderly individuals with limited access to social and health resources and with low SOC may be a group at risk for dependence and disability in Spain
Intratumoral BO-112 in combination with radiotherapy synergizes to achieve CD8 T-cell-mediated local tumor control
Get PDFBackgroundRadioimmunotherapy combines irradiation of tumor lesions with immunotherapy to achieve local and abscopal control of cancer. Most immunotherapy agents are given systemically, but strategies for delivering immunotherapy locally are under clinical scrutiny to maximize efficacy and avoid toxicity. Local immunotherapy, by injecting various pathogen-associated molecular patterns, has shown efficacy both preclinically and clinically. BO-112 is a viral mimetic based on nanoplexed double-stranded RNA (poly I:C) which exerts immune-mediated antitumor effects in mice and humans on intratumoral delivery. BO-112 and focal irradiation were used to make the proof-of-concept for local immunotherapy plus radiation therapy combinations.MethodsMurine transplantable tumor cell lines (TS/A, MC38 and B16-OVA) were used to show increased immunogenic features under irradiation, as well as in bilateral tumor models in which only one of the lesions was irradiated or/and injected with BO-112. Flow cytometry and multiplex tissue immunofluorescence were used to determine the effects on antitumor immunity. Depletions of immune cell populations and knockout mice for the IFNAR and BATF-3 genes were used to delineate the immune system requirements for efficacy.ResultsIn cultures of TS/A breast cancer cells, the combination of irradiation and BO-112 showed more prominent features of immunogenic tumor cell death in terms of calreticulin exposure. Injection of BO-112 into the tumor lesion receiving radiation achieved excellent control of the treated tumor and modest delays in contralateral tumor progression. Local effects were associated with more prominent infiltrates of antitumor cytotoxic tumor lymphocytes (CTLs). Importantly, local irradiation plus BO-112 in one of the tumor lesions that enhanced the therapeutic effects of radiotherapy on distant irradiated lesions that were not injected with BO-112. Hence, this beneficial effect of local irradiation plus BO-112 on a tumor lesion enhanced the therapeutic response to radiotherapy on distant non-injected lesions.ConclusionThis study demonstrates that local BO-112 immunotherapy and focal irradiation may act in synergy to achieve local tumor control. Irradiation plus BO-112 in one of the tumor lesions enhanced the therapeutic effects on distant irradiated lesions that were not injected with BO-112, suggesting strategies to treat oligometastatic patients with lesions susceptible to radiotherapy and with at least one tumor accessible for repeated BO-112 intratumoral injections
p53 regulation by MDM2 contributes to self-renewal and differentiation of basal stem cells in mouse and human airway epithelium
No full textProper physiological function of mammalian airways requires the differentiation of basal stem cells into secretory or multiciliated cells, among others. In addition, the self- renewal ability of these basal stem cells is crucial for developing a quick response to toxic agents in order to re- establish the epithelial barrier function of the airways. Although these epithelial missions are vital, little is known about those mechanism controlling airway epithelial regeneration in health and dis-ease. p53 has been recently proposed as the guardian of homeostasis, promoting differentiation programs, and antagonizing a de- differentiation program. Here, we exploit mouse and human tracheal epithelial cell culture models to study the role of MDM2- p53 signaling in self- renewal and differentiation in the airway epi-thelium. We show that p53 protein regulation by MDM2 is crucial for basal stem cell differentiation and to keep proper cell proliferation. Therefore, we suggest that MDM2/p53 interaction modulation is a potential target to control regenera-tion of the mammalian airway epithelia without massively affecting the epithe-lium integrity and differentiation potential.J.M.C.- G. was recipient of a Ramón y Cajal contract (RYC- 2015- 17867). This work was supported by BFU2014- 54699- P, BFU2017- 85547- P grants from the Ministry of Economy, and IB18014 from Junta de Extremadura to J.M.C.- G. and GR15164 from Junta de Extremadura to F.C. S.G.- J. was a recipient of a Fellowship from the Universidad de Extremadura. S.D.- Ch. and C.M.M.- Q. were recipients of a Fellowship from Junta de Extremadura. All Spanish fund-ing is co- sponsored by the European Union FEDER program.peerReviewe
Neutrophil Extracellular Traps, Local IL-8 Expression, and Cytotoxic T-Lymphocyte Response in the Lungs of Patients With Fatal COVID-19
Get PDFBACKGROUND: Excessive inflammation is pathogenic in the pneumonitis associated with severe COVID-19. Neutrophils are among the most abundantly present leukocytes in the inflammatory infiltrates and may form neutrophil extracellular traps (NETs) under the local influence of cytokines. NETs constitute a defense mechanism against bacteria, but also have been shown to mediate tissue damage in a number of diseases. RESEARCH QUESTION: Could NETs and their tissue-damaging properties inherent to neutrophil-associated functions play a role in the respiratory failure seen in patients with severe COVID-19, and how does this relate to the SARS-CoV-2 viral loads, IL-8 (CXCL8) chemokine expression, and cytotoxic T-lymphocyte infiltrates? STUDY DESIGN AND METHODS: Sixteen lung biopsy samples obtained immediately after death were analyzed methodically as exploratory and validation cohorts. NETs were analyzed quantitatively by multiplexed immunofluorescence and were correlated with local levels of IL-8 messenger RNA (mRNA) and the density of CD8+ T-cell infiltration. SARS-CoV-2 presence in tissue was quantified by reverse-transcriptase polymerase chain reaction and immunohistochemistry analysis. RESULTS: NETs were found in the lung interstitium and surrounding the bronchiolar epithelium with interindividual and spatial heterogeneity. NET density did not correlate with SARS-CoV-2 tissue viral load. NETs were associated with local IL-8 mRNA levels. NETs also were detected in pulmonary thrombi and in only one of eight liver tissues. NET focal presence correlated negatively with CD8+ T-cell infiltration in the lungs. INTERPRETATION: Abundant neutrophils undergoing NETosis are found in the lungs of patients with fatal COVID-19, but no correlation was found with viral loads. The strong association between NETs and IL-8 points to this chemokine as a potentially causative factor. The function of cytotoxic T-lymphocytes in the immune responses against SARS-CoV-2 may be interfered with by the presence of NETs
Seven-versus 14-day course of antibiotics for the treatment of bloodstream infections by Enterobacterales: a randomized, controlled trial
Get PDF[Objective] To prove that 7-day courses of antibiotics for bloodstream infections caused by members of the Enterobacterales (eBSIs) allow a reduction in patients' exposure to antibiotics while achieving clinical outcomes similar to those of 14-day schemes.[Methods] A randomized trial was performed. Adult patients developing eBSI with appropriate source control were assigned to 7 or 14 days of treatment, and followed 28 days after treatment cessation; treatments could be resumed whenever necessary. The primary endpoint was days of treatment at the end of follow-up. Clinical outcomes included clinical cure, relapse of eBSI and relapse of fever. A superiority margin of 3 days was set for the primary endpoint, and a non-inferiority margin of 10% was set for clinical outcomes. Efficacy and safety were assessed together with a DOOR/RADAR (desirability of outcome ranking and response adjusted for duration of antibiotic risk) analysis.[Results] 248 patients were assigned to 7 (n = 119) or 14 (n = 129) days of treatment. In the intention-to-treat analysis, median days of treatment at the end of follow-up were 7 and 14 days (difference 7, 95%CI 7–7). The non-inferiority margin was also met for clinical outcomes, except for relapse of fever (–0.2%, 95%CI –10.4 to 10.1). The DOOR/RADAR showed that 7-day schemes had a 77.7% probability of achieving better results than 14-day treatments.[Conclusions] 7-day schemes allowed a reduction in antibiotic exposure of patients with eBSI while achieving outcomes similar to those of 14-day schemes. The possibility of relapsing fever in a limited number of patients, without relevance to final outcomes, may not be excluded, but was overcome by the benefits of shortening treatments.This work received technical support from the Spanish Network of Research in Infectious Diseases (REIPI) and the Spanish Clinical Research Network (SCReN) of the Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Spanish Government (PT13/0002/0010).Peer reviewe
