How do Cooperation and Scientific Research Influence Drug Development? The Case of Cancer Disease

[ES] Más del 90 por ciento de los ensayos clínicos de medicamentos contra el cáncer fracasan. Por tanto, es necesario mejorar el conocimiento sobre los factores que aumentan el éxito del desarrollo de medicamentos. En esta tesis, se aborda esta cuestión desde la perspectiva de los Estudios de Innovación. Para ello, se revisa sistemáticamente 103 artículos relacionados con ensayos clínicos, publicados en revistas de innovación (1984-2021). Así se logra sintetizar los hallazgos existentes, clasificar los estudios por categorías y proporcionar algunas sugerencias teóricas y metodológicas para trabajos futuros. Se encuentra que las teorías del ciclo de vida del producto y de la innovación del usuario deberían ser aplicadas en la investigación futura para mejorar la compresión sobre el desarrollo de medicamentos. Se recomienda un mayor uso de los análisis causales, de regresión y de metodologías mixtas, especialmente en relación con los temas de la comercialización, la transferencia de conocimiento y los marcos institucionales, así como un mejor uso del aprendizaje automático y los lenguajes de programación por lo que se refiere a las herramientas informáticas de recogida de datos. De acuerdo con las lagunas de investigación identificadas en la revisión de la literatura, se explora el papel de la radicalidad, la formación de redes, la naturaleza básica y el impacto científico de la investigación en el éxito del desarrollo de fármacos a través de ensayos clínicos. Los resultados muestran que un mayor grado de radicalidad es menos susceptible de conducir al éxito. La relación entre densidad de la red y la tasa de éxito sigue una forma de U invertida. En redes de cooperación más densas, las organizaciones radicales tienen más posibilidades de éxito. El desarrollo radical de medicamentos implica que las organizaciones asuman más riesgos, lo que da lugar a más fracasos; sin embargo, una manera efectiva de incrementar la tasa de éxito del desarrollo radical de medicamentos es mediante la promoción de la densidad de las redes de cooperación. La investigación aplicada facilita que las organizaciones se involucren en el desarrollo de medicamentos, y la investigación básica es útil para incrementar la tasa de éxito del desarrollo de medicamentos. No obstante, la investigación aplicada de los cooperantes también incrementa la tasa de éxito a través de los efectos desbordamiento de la red. El impacto científico de la investigación juega un papel positivo tanto en involucrarse en el desarrollo de medicamentos como en conducirlo al éxito, directamente y través de los efectos desbordamiento de la red. Esta tesis proporciona algunas ideas para aumentar la tasa de éxito del desarrollo de medicamentos para organizaciones médicas y formuladores de políticas a través de estrategias de ciencia, cooperación e innovación.[CAT] Més del 90 per cent dels assajos clínics de fàrmacs contra el càncer fracassen. Per tant, és necessari millorar el coneixement sobre els factors que augmenten l'èxit del desenvolupament de fàrmacs. En aquesta tesi, s'aborda aquesta qüestió des de la perspectiva dels Estudis d'Innovació. Per a això, es revisa sistemàticament 103 articles relacionats amb assajos clínics, publicats en revistes d'innovació (1984-2021). Així s'aconsegueix sintetitzar les troballes existents, classificar els estudis per categories i proporcionar alguns suggeriments teòrics i metodològics per a treballs futurs. Es troba que les teories del cicle de vida del producte i de la innovació de l'usuari haurien de ser aplicades en la investigació futura per a millorar la compressió sobre el desenvolupament de fàrmacs. Es recomana un major ús de les anàlisis causals, de regressió i de metodologies mixtes, especialment en relació amb els temes de la comercialització, la transferència de coneixement i els marcs institucionals, així com un millor ús de l'aprenentatge automàtic i els llenguatges de programació pel que fa a les eines informàtiques de recollida de dades. D'acord amb les llacunes d'investigació identificades en la revisió de la literatura, s'explora el paper de la radicalitat, la formació de xarxes, la naturalesa bàsica i l'impacte científic de la investigació en l'èxit del desenvolupament de fàrmacs a través d'assajos clínics. Els resultats mostren que un major grau de radicalitat és menys susceptible de conduir a l'èxit. La relació entre densitat de la xarxa i la taxa d'èxit segueix una forma d'U invertida. En xarxes de cooperació més denses, les organitzacions radicals tenen més possibilitats d'èxit. El desenvolupament radical de fàrmacs implica que les organitzacions assumisquen més riscos, la qual cosa dona lloc a més fracassos; no obstant això, una manera efectiva d'incrementar la taxa d'èxit del desenvolupament radical de fàrmacs és mitjançant la promoció de la densitat de les xarxes de cooperació. La investigació aplicada facilita que les organitzacions s'involucren en el desenvolupament de fàrmacs, i la investigació bàsica és útil per a incrementar la taxa d'èxit del desenvolupament de fàrmacs. No obstant això, la investigació aplicada dels cooperants també incrementa la taxa d'èxit a través dels efectes desbordament de la xarxa. L'impacte científic de la investigació juga un paper positiu tant a involucrar-se en el desenvolupament de fàrmacs com a conduir-lo a l'èxit, directament i través dels efectes desbordament de la xarxa. Aquesta tesi proporciona algunes idees per a augmentar la taxa d'èxit del desenvolupament de fàrmacs per a organitzacions mèdiques i formuladors de polítiques a través d'estratègies de ciència, cooperació i innovació.[EN] Over 90% of clinical trials for cancer disease drugs fail. It is therefore necessary to increase understanding about the factors that increase the success of drug development. In the present thesis, this issue is addressed from the perspective of Innovation Studies. To this end, 103 articles related to clinical trials, published in innovation journals (1984-2021), are revised systematically. The existing findings are summarised, the studies are classified into categories and some suggestions for potential theoretical and methodological advances in Innovation Studies are provided. It is found that product life cycle and user innovation theories should be applied in future research to improve understanding about drug development. Further use of causal, regression and mixed-methods analysis is also recommended, especially related to the topics of commercialisation, knowledge transfer and institutional frameworks, along with a better use of machine learning and programming languages with regards to data gathering computer tools. Based on the research gaps identified in the literature review, an exploration is made of the role of radicalness, network formation, and the basicness and scientific impact of research on the success of drug development through clinical trials. The results show that a greater degree of radicalness is less likely to achieve success. The relationship between network density and success rate follows an inverted U-shape. In denser cooperation networks, radical organisations have a greater possibility of achieving success. Radical drug development involves organisations taking more risks, which results in more failures; however, an effective way of increasing the success rate of radical drug development is by promoting cooperation network density. Applied research encourages organisations to engage in drug development, and basic research is useful for increasing the success rate of drug development. Nevertheless, the applied research of cooperators also increases the success rate through network spillovers. The scientific impact of research plays a positive role in both the engagement and success of drug development, directly and through network spillovers. This thesis provides some insights to increase the success rate of drug development for medical organisations and policymakers through science, cooperation and innovation strategies.I want to gratefully acknowledge the support from Spanish Ministry of Science, Innovation and Universities through Project CSO2016-79045-C2-2-R of the Spanish National R&D&I Plan, and Project AICO/2021/021 of the Valencian Government. The Universitat Politècnica de València funded my research through Contratos Pre-Doctorales UPV 2018 and Mobility Grants UPV 2019.Li, S. (2023). How do Cooperation and Scientific Research Influence Drug Development? The Case of Cancer Disease [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/19638

Tropical Cyclone Wind Hazard Assessment for Southeast Part of Coastal Region of China

Tropical cyclone (TC) or typhoon wind hazard and risk are significant for China. The return period value of the maximum typhoon wind speed is used to characterize the typhoon wind hazard and assign wind load in building design code. Since the historical surface observations of typhoon wind speed are often scarce and of short period, the typhoon wind hazard assessment is often carried out using the wind field model and TC track model. For a few major cities in the coastal region of mainland China, simple or approximated wind field models and a circular subregion method (CSM) have been used to assess the typhoon wind hazard in different studies. However, there are differences among the values given by these studies and by the Chinese building design code. Moreover, there is a lack of a TC full track model simulating the TC from genesis to lysis developed for China. A TC full track model and a planetary wind field model (PBL) have been applied to assess the hurricane wind hazard for the U.S. and used to update the U.S. design code. This study finds this PBL wind field model is approximated and the effect of such approximation on the estimated hurricane wind hazards needs to be investigated. By using the best track dataset given by HURDAT, the TC full track model and a simplified version are developed for the U.S. The performance of the simplified TC full track model is verified and found to be comparable with the full version. For assessing the typhoon wind hazard for China, the best track dataset released from China Meteorological Administration (CMA) is used. The PBL wind field model is used with the CSM to assess a few coastal cities of mainland China. The practice is extended to cover the whole region of the southeast part of mainland China to develop the contour maps of the typhoon wind hazards. By using the CMA best track dataset, a full track model is developed for the western North Pacific basin. This full track model is combined again with the PBL wind field model to assess the typhoon wind hazard for mainland China. The results obtained by using the full track model are compared to those estimated by using CSM, by using long term ground observations and tabulated in the Chinese building code

Targeted Test Generation for Actor Systems

This paper addresses the problem of targeted test generation for actor systems. Specifically, we propose a method to support generation of system-level tests to cover a given code location in an actor system. The test generation method consists of two phases. First, static analysis is used to construct an abstraction of an entire actor system in terms of a message flow graph (MFG). An MFG captures potential actor interactions that are defined in a program. Second, a backwards symbolic execution (BSE) from a target location to an "entry point" of the actor system is performed. BSE uses the MFG constructed in the first phase of our targeted test generation method to guide execution across actors. Because concurrency leads to a huge search space which can potentially be explored through BSE, we prune the search space by using two heuristics combined with a feedback-directed technique. We implement our method in Tap, a tool for Java Akka programs, and evaluate Tap on the Savina benchmarks as well as four open source projects. Our evaluation shows that the Tap achieves a relatively high target coverage (78% on 1,000 targets) and detects six previously unreported bugs in the subjects

I. Selective Chlorination and Fluorination of Quinols II. Synthetic Study of Strongylophorine-26

Organic compounds containing halogen are an important and useful class of intermediates that can be converted to other functionalities. This thesis describes our strategy in selective chlorination and fluorination of quinols to offer the corresponding aromatic structures. Quinols, or cyclohexadienones, as oxidized derivatives of phenols, have their remarkable chemical reactivities, including additions to enone, enolate alkylations, aldol reactions, cycloadditions, and rearrangements. Dienone-phenol rearrangement provides the asymmetric route since the stereocenters located in the six-membered ring of various cyclohexadienone were widely using in building larger chiral arrays for many total syntheses Chapter one of this thesis discusses our new selective nucleophilic chlorination of quinol to afford ortho- chloride phenol. This one-step selective chlorination can easily be performed using readily available quinols and thionyl chloride. In Chapter two, inspired by chlorination strategy, we develop a new fluorination strategy to offer fluorinated cyclohexadienone products by deoxofluorination of quinols. Chapter three describes our study work on the total synthesis of Strongylophorine-26. The difficulties we met and our solution is discussed

Building a Cultural and Creative Industry Platform to Serve the Economic Development

With the rise of global integration of science, technology economy and cultural creative industries develop rapidly. Under the circumstance of rapid development, how to train the development of cultural creative industries talents has become a key factor problem of prosperity society. Institutions of higher learning undertake the four functions of talent training, scientific research, social service cultural inheritance and innovation. Therefore, it is necessary to build a research platform for cultural and creative industry of the college. This platform is not only help graduates find their future employment direction, but also effectively help them to obtain employment and start businesses. At the same time, the platform is used to enhance the integration with local industry development and promote the local economy development, which not only meets the development of college, but also meets the needs of local governments and enterprises. This mode of training talents for government-industry-university-research cooperation meets the interest demands of the government, industry and school, and serves the development of local economy together. Keywords: Cultural Creative Product; Talent Cultivation; Local Economic; Economic Development. eISSN: 2398-4287 © 2022. The Authors. Published for AMER ABRA cE-Bs by e-International Publishing House, Ltd., UK. This is an open-access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under the responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians), and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning & Surveying, Universiti Teknologi MARA, Malaysia. DOI: https://doi.org/10.21834/ebpj.v7iSI7.377

Building specific catastrophe modeling for mid/high rise buildings supported by wind tunnel data

Catastrophe modeling has been widely used to optimize portfolio management and facilitate public decision making for hazard mitigation. Among different natural perils, wind hazard imposed risk is one of the most significant. Three main aspects involved in catastrophe modeling includes hazard quantification, vulnerability assessment and monetary/economic impact prediction. Hazard quantification has been advanced in past decades due to advanced observational records, more powerful computational facilities and extensive research activities. Exposure data used for predicting monetary impact is also improved with more information collected. The estimation of building component failure includes significant uncertainties for mid/high rise buildings located in those coastal metropolitans, when generic models are applied. It is common for mid/high rise commercial buildings that geometry is unique and irregular and the surrounding building conditions are complex. Typically, wind tunnel tests are conducted to obtain accurate design pressures for cladding system and structural wind loads. Code calculated wind pressures are often used in modeling risk of building envelope breach when a generic model is considered. However, due to the complexity of the surrounding buildings and unique geometry of the building, code calculated pressures could introduce large uncertainties for specific buildings. The measured pressure distribution from the wind tunnel for specific building can be used to accurately quantify the risk of building envelope breach, which is one of the key failure modes for mid/high rise buildings. Structural failure is typically not being modeled for mid/high rise engineered buildings. However, there is still chances that the structural damage could occur at very high wind speed. The impact of considering the structural failure is investigated in this study. The developed vulnerability curve based on pressure calculated for generic model is compared to that developed by using building specific dataset