Tesis por compendio / [ES] El brote de Coronavirus SARS-CoV-2 representó un reto para la economía, la vida social y los servicios sanitarios. Justo cuando más se necesitaba la información para la planificación económica, los servicios de vigilancia y notificación no fueron capaces de ofrecer, a pesar de esfuerzos extraordinarios, datos consistentes, como así reconocieron los propios orga-nismos gubernamentales. Esta tesis incluye tres artículos publicados durante los brotes de COVID-19 y una investi-gación adicional fuera del conjunto de publicaciones. La investigación tiene como objetivo general proporcionar información a través de estimaciones alternativas. Para ello se han utilizado varias metodologías, entre ellas los modelos matemáticos de predicción epidemio-lógica, el Mejor Ajuste de Valores Relacionados (BARV), los análisis de diferentes encues-tas y la metodología bibliométrica, aprovechando u ofreciendo alternativas a los métodos bayesianos más complejos, las simulaciones de Monte Carlo o las cadenas de Markov, aun-que algunos datos obtenidos se apoyan parcialmente en estas metodologías. Cada artículo aborda un tema esencial relacionado con la pandemia COVID-19. La primera publicación se centra en los datos epidemiológicos básicos. Se refiere al primer brote de COVID-19, estimando su duración, incidencia, prevalencia, tasa de fallecimientos sobre infectados (IFR) y tasa de fallecimientos sobre casos (confirmados) (CFR). Como dato destacado de este trabajo, se previó que la seroprevalencia era demasiado baja para que la inmunidad de rebaño desempeñara algún papel. Aunque el valor obtenido fue aproxima-damente un 2% inferior al que demostró posteriormente un estudio poblacional (Instituto Carlos III), la conclusión sobre la inmunidad de rebaño no cambió, y los resultados confir-maron la idoneidad del enfoque. La segunda publicación se centró en las cuestiones legales y las noticias falsas, analizando la reticencia de la población a vacunarse, el impacto de las falsas noticas en estos comporta-mientos, las posibilidades legales de hacer obligatoria la vacuna y las posibles acciones contra los profesionales de la salud que publican noticias falsas. La principal conclusión fue que, aunque se podría encontrar una vía legal para la obligatoriedad de la vacunación, y para la persecución gubernamental de las noticias falsas, la opinión ciudadana parece prefe-rir que la administración no tome la iniciativa, por lo que se recomienda promover y fomen-tar la concienciación ciudadana. La tercera publicación presentó un modelo matemático simplificado para la estimación del coste-efectividad de la vacuna contra la COVID-19. Se actualizan los datos de dos fechas para la estimación de los costes directos para el sistema sanitario debidos a la COVID-19, computando el coste por ciudadano y por Producto Interior Bruto (PIB), así como el coste-efectividad de la vacuna. La estimó razón de coste-efectividad incremental (RCEI) para dos dosis por persona a un coste de 30 euros cada dosis (incluida la administración). Asumien-do al 70% de efectividad y con el 70% de la población vacunada resultó ser de 5.132 euros (4.926 - 5.276) por año de vida ajustado a calidad (AVAC) ganado (a 17 de febrero de 2021). Una cifra que desciende cada día de pandemia activa. Se incluyó una investigación adicional, no incorporada en el conjunto de artículos, centrada en los recursos humanos y la educación. Se analizaron los temas preocupan al personal de primera línea, es decir, a la enfermería, y cómo la pandemia ha afectado a sus publicaciones científicas, como índice de los cambios en el clima laboral que sufre este colectivo. Median-te un estudio bibliométrico comparativo entre las publicaciones de 2019 y 2020, se analizó el cambio de temas y ámbitos como reflejo del impacto del COVID-19 en el personal de enfermería. Así se comprobó que, en los ámbitos de enfermería de atención especializada, y sobre todo e / [CA] El brot de Coronavirus SARS-CoV-2 va representar un repte per a l'economia, la vida soci-al i els serveis sanitaris. Quan més es necessitava la informació per a la planificació econò-mica, malgrat esforços extraordinaris, els serveis de vigilància i notificació no van ser capa-ços d'oferir dades consistents, com així van reconèixer els mateixos organismes governa-mentals. Aquesta tesi inclou tres articles publicats durant els brots de COVID-19 i una investigació addicional fora del conjunt de publicacions. La investigació té com a objectiu general pro-porcionar informació a través d'estimacions alternatives. Per a això s'han utilitzat diverses metodologies, entre elles els models matemàtics de predicció epidemiològica, el Millor Ajust de Valors Relacionats (BARV), les anàlisis de diferents enquestes i la metodologia bibliomètrica, aprofitant o oferint opcions alternatives als mètodes bayesians més comple-xos, les simulacions de Montecarlo o les cadenes de Markov, tot i que algunes dades obtin-gudes es recolzen parcialment en aquestes metodologies. Cada article aborda un tema essen-cial relacionat amb la pandèmia COVID-19. La primera publicació se centra en les dades epidemiològiques bàsiques. Es refereix al pri-mer brot de COVID-19, calculant la seua durada, incidència, prevalença, taxa de defuncions sobre infectats (IFR) i taxa de defuncions sobre casos (confirmats) (CFR). Com a dada des-tacada d'aquest treball, es va preveure que la seroprevalença era massa baixa perquè la im-munitat de ramat exercirà algun paper. Tot i que el valor obtingut va ser aproximadament un 2% inferior al demostrat posteriorment en un estudi poblacional (Institut Carles III), la conclusió sobre la immunitat de ramat no va canviar, i els resultats van confirmar la idoneï-tat de l'enfocament. La segona publicació es va centrar en les qüestions legals i les notícies falses, analitzant la reticència de la població a vacunar-se, l'impacte de les falses notícies en aquests comporta-ments, les possibilitats legals de fer obligatòria la vacuna i les possibles accions contra els professionals de la salut que publiquen notícies falses. La principal conclusió va ser que, tot i que es podria trobar una via legal per l'obligatorietat de la vacunació, i per la persecució governamental de les notícies falses, l'opinió ciutadana sembla preferir que l'administració no prenga la iniciativa, per la qual cosa es recomana promoure i fomentar la conscienciació ciutadana. La tercera publicació va presentar un model matemàtic simplificat per a l'estimació del cost-efectivitat de la vacuna contra la COVID-19. S'actualitzen les dades de dues dates per a l'estimació dels costos directes per al sistema sanitari deguts a la COVID-19, computant el cost per ciutadà i per Producte Interior Brut (PIB), així com el cost-efectivitat de la vacuna. La va estimar raó de cost-efectivitat incremental (RCEI) per dues dosis per persona a un cost de 30 euros cada dosi (inclosa l'administració). Assumint al 70% d'efectivitat i amb el 70% de la població vacunada va resultar ser de 5.132 euros (4.926 - 5.276) per any de vida ajustat a qualitat (AVAQ) (a 17 de febrer de 2021). Una xifra que descendeix cada dia de pandèmia activa. Es va afegir una investigació addicional, no inclosa en el conjunt d'articles, centrada en els recursos humans i l'educació. Es van analitzar els temes que preocupen al personal de pri-mera línia, és a dir, a la infermeria, i com la pandèmia ha afectat les seues publicacions cien-tífiques, com a índex dels canvis en el clima laboral que pateix aquest col·lectiu. Mitjançant un estudi bibliomètric comparatiu entre les publicacions de 2019 i 2020, es va analitzar el canvi de temes i camps com a reflex de l'impacte del COVID-19 en el personal d'infermeria. Així es va comprovar que en els àmbits d'infermeria d'atenció especialitzada, i sobretot en atenció primària, els principals problemes detectat / [EN] The SARS-CoV-2 Coronavirus outbreak has posed a challenge to the economy, social life, and health services. Just when information was most needed for economic planning, moni-toring, and reporting services were unable, despite extraordinary efforts to provide con-sistent data, as government agencies themselves acknowledged. This thesis includes three articles published during the COVID-19 outbreaks and additional research outside the publication set. The overall aim of the research is to provide infor-mation through alternative estimates. Several methodologies have been used, including mathematical models for epidemiological prediction, Best Adjustment of Related Values (BARV), analyses of different surveys and bibliometric methodology, taking advantage of or offering an alternative to, more complex options such as Bayesian methods, Monte Carlo simulations or Markov chains, although some data obtained are partially supported by these methodologies. Each article addresses a key issue related to the COVID-19 pandemic. The first publication focuses on basic epidemiological data. It refers to the first outbreak of COVID-19, estimating its duration, incidence, prevalence, Infection Fatality Rate (IFR) and Case Fatality Rate (CFR). As a highlight of this work, the seroprevalence was anticipated to be too low for herd immunity to play a role. Although the value obtained was approximate-ly 2% lower than that subsequently demonstrated by a population-based study (Instituto Carlos III), the conclusion on herd immunity remained unchanged, and the results con-firmed the appropriateness of the approach. The second publication focuses on legal issues and fake news, analysing reluctance to be vaccinated in the population, the impact of fake news on these behaviours, the legal possi-bilities of making vaccination mandatory, and possible actions against health professionals who publish fake news. The main conclusion was that, although a legal avenue could be found for mandatory vaccination and for governmental prosecution of fake news, public opinion seems to prefer that the authorities do not take the initiative, therefore it recom-mends promoting and encouraging public awareness. The third publication presented a simplified mathematical model for estimating the cost-effectiveness of the COVID-19 vaccine. Data from two dates were obtained for the estimation of the direct costs to the health system due to COVID-19, computing the cost per citizen and per Gross Domestic Product (GDP), as well as the cost-effectiveness of the vaccine. The estimated incremental cost-effectiveness ratio (ICER) was calculated for two doses per person at a cost of 30 euros per dose (including administration). Assuming 70% effectiveness and with 70% of the population vaccinated, it was found to be 5,132 euros (4,926 - 5,276) per quality-adjusted life year (QALY) gained (as of 17 February 2021). The figure decreases with each day of the active pandemic. Additional research not included in the set of articles focuses on human resources and education. It analyses the concerns of frontline staff, i.e., nurses, and how the pandemic has affected their scientific publications, as an index of the changes in the work climate experienced by this group. Through a comparative bibliometric study of publications in 2019 and 2020, the change in topics and fields was analysed, as a reflection of the impact of COVID-19 on nursing staff. It was found that in the fields of specialised care nursing and above all in primary care, the main problems detected are those related to protective measures and psychological factors, while the publications of nursing staff in nursing homes showed an increase in topics related to management and organisation. Finally, some aspects of the implementation of telecommuting and distance learning have been reviewed. Some of the boosts in this field resulting from the pandemic could be very useful and remain in the future, such as the incorporation of telewo / Marco Franco, JE. (2021). What have we learned from the economic impact of the Covid-19 outbreak? Critical analysis of economic factors and recommendations for the future [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/174883 / Compendio

Ciliary neurotrophic factor (CNTF) is produced by astrocytes which have been implicated in regulating stress responses. We found that CNTF in the medial amygdala (MeA) promotes despair or passive coping, i.e., immobility in an acute forced swim stress, in female mice, while having no effect in males. Neutralizing CNTF antibody injected into the MeA of wildtype females reduced activation of downstream STAT3 (Y705) 24 and 48 h later. In concert, the antibody reduced immobility in the swim test in females and only after MeA injection, but not when injected in the central or basolateral amygdala. Antibody injected into the male MeA did not affect immobility. These data reveal a unique role of CNTF in female MeA in promoting despair or passive coping behavior. Moreover, 4 weeks of chronic unpredictable stress (CUS) increased immobility in the swim test and reduced sucrose preference in wildtype CNTF+/+, but not CNTF-/- littermate, females. Following CUS, 10 min of restraint stress increased plasma corticosterone levels only in CNTF+/+ females. In males, the CUS effects were present in both genotypes. Further, CUS increased CNTF expression in the MeA of female, but not male, mice. CUS did not alter CNTF in the female hippocampus, hypothalamus and bed nucleus of stria terminalis. This suggests that MeA CNTF has a female-specific role in promoting CUS-induced despair or passive coping, behavioral anhedonia and neuroendocrine responses. Compared to CNTF+/+ mice, CNTF-/- mice did not show differences in CUS-induced anxiety-like behavior and sensorimotor gating function as measured by elevated T-Maze, open field and pre-pulse inhibition of the acoustic startle response. Together, this study reveals a novel CNTF-mediated female-specific mechanism in stress responses and points to opportunities for developing treatments for stress-related disorders in women.

Excessive unobserved firepower expenditures by Allied forces during the Vietnam War defied the traditional counterinsurgency principle that population protection should be valued more than destruction of the enemy. Many historians have pointed to this discontinuity in their arguments, but none have examined the available firepower records in detail. This study compiles and analyzes available, artillery-related U.S. and Allied archival records to test historical assertions about the balance between conventional and counterinsurgent military strategy as it changed over time. It finds that, between 1965 and 1970, the commanders of the U.S. Military Assistance Command, Vietnam (MACV), Generals William Westmoreland and Creighton Abrams, shared significant continuity of strategic and tactical thought. Both commanders tolerated U.S. Army, Marine Corps, and Allied unobserved firepower at levels inappropriate for counterinsurgency and both reduced Army harassment and interdiction fire (H&I) as a response to increasing budgetary pressure. Before 1968, the Army expended nearly 40 percent of artillery ammunition as H&I – a form of unobserved fire that sought merely to hinder enemy movement and to lower enemy morale, rather than to inflict any appreciable enemy casualties. To save money, Westmoreland reduced H&I, or “interdiction” after a semantic name change in February 1968, to just over 29 percent of ammunition expended in July 1968, the first full month of Abrams’ command. Abrams likewise pursued dollar savings with his “Five-by-Five Plan” of August 1968 that reduced Army artillery interdiction expenditures to nearly ten percent of ammunition by January 1969. Yet Abrams allowed Army interdiction to stabilize near this level until early 1970, when recurring financial pressure prompted him to virtually eliminate the practice. Meanwhile, Marines fired H&I at historically high rates into the final months of 1970 and Australian “Harassing Fire” surpassed Army and Marine Corps totals during the same period. South Vietnamese artillery also fired high rates of H&I, but Filipino and Thai artillery eschewed H&I in quiet areas of operation and Republic of Korea [ROK] forces abandoned H&I in late 1968 as a direct response to MACV’s budgetary pressure. Financial pressure, rather than strategic change, drove MACV’s unobserved firepower reductions during the Vietnam War.