Efficient evaluation of a continued fraction

Technical Report DEIOAC-2020-01This document presents a pseudocode routine to calculate the term C(a,z) described in the work by Giner-Bosch, Tran, Castagliola and Khoo [Qual. Reliab. Eng. Int. 35 (2019), pp. 1515–1541].Giner Bosch, V. (2020). Efficient evaluation of a continued fraction involved in the calculation of the moments of the sample multivariate coefficient of variation squared. http://hdl.handle.net/10251/15681

Precontrol óptimo. Caracterización, análisis y técnicas de resolución

El precontrol es una herramienta para el control de la calidad que tiene como objeto evaluar la aptitud de un proceso para producir piezas dentro de unas especificaciones dadas. Es usada, entre otros contextos, en la validación de la puesta a punto de procesos con ciclos de ejecución cortos. Basa su funcionamiento en la comparación de las sucesivas observaciones individuales muestreadas frente a los límites de tolerancia y los llamados límites de precontrol, y utiliza conteos acumulados para emitir un juicio sobre la validez del proceso. Es una técnica sencilla, rápida y fácil de aplicar. El hecho de que, en su versión original, la técnica del precontrol no tenga en cuenta la variabilidad natural del proceso objeto de monitorización, unido a la sencillez de su diseño, provocan que, bajo ciertas circunstancias, su comportamiento no sea tan eficaz como sería deseable, en términos de la tasa de falsa alarma y de la potencia para detectar desviaciones inaceptables, hasta el punto de que algunos autores rechazan su uso. En este sentido, existen en la literatura diversas propuestas encaminadas a mejorar el comportamiento de la técnica original mediante la modificación, en mayor o menor medida, de sus reglas de funcionamiento. En esta tesis doctoral se aborda la mejora del precontrol como herramienta para la cualificación de procesos, a través de la determinación óptima de los parámetros que rigen su comportamiento, utilizando técnicas de programación no lineal entera mixta. El objetivo es desarrollar una metodología para automatizar el proceso de elección del valor de los parámetros del precontrol, de manera que éste se ajuste lo mejor posible a los requerimientos del usuario. Este enfoque de Optimización, inédito en el precontrol, ha sido aplicado con éxito a otras técnicas de control de la calidad en las últimas décadas, permitiendo obtener mejores herramientas para la toma de decisiones. Para ello, en primer lugar se realiza una revisión exhaustiva de las diferentes propuestas existentes en la literatura en torno al precontrol. Posteriormente, se define el problema a resolver y se desarrolla un modelo de programación matemática específico para la obtención de los denominados planes de precontrol óptimos. Se realiza una completa experiencia numérica con software de optimización de propósito general, mediante la que se evidencia la eficacia del modelo propuesto y, al mismo tiempo, se pone de manifiesto la existencia de diferencias significativas entre los resultados proporcionados por los diferentes algoritmos tomados en consideración, debidas en parte a la doble naturaleza no lineal y entera del problema, así como la incapacidad de dichos algoritmos para garantizar la convergencia a un óptimo global, a causa de la existencia de no convexidades. Todo ello justifica el diseño de algoritmos específicos para la obtención de planes de precontrol óptimos, tarea que también se aborda en la presente tesis doctoral. Previamente, se realiza un estudio de las propiedades matemáticas del modelo de optimización construido, que permite ampliar el conocimiento sobre el problema del precontrol óptimo. Este conocimiento es empleado en la elaboración de un algoritmo exacto para la resolución de dicho problema, denominado OPCenum, el cual combina una estrategia enumerativa implícita con una búsqueda local basada en métodos de búsqueda de raíces sin uso de derivadas. El algoritmo es implementado y probado sobre la misma batería de ejemplos que conformaban la experiencia numérica anterior. Las pruebas revelan la eficacia y eficiencia del algoritmo OPCenum como método para la obtención de planes de precontrol óptimos a partir de unos requerimientos dados. La elaboración de una interfaz gráfica para hacer más accesible el algoritmo al usuario final, la adaptación del problema a funciones de distribución asimétricas y a ámbitos como el de la fiabilidad, así como el desarrollo de un enfoque paralelo al acometido aquí en el que se considere el precontrol como herramienta para validar la capacidad del proceso destacan como líneas futuras de investigación que surgen a partir de los resultados obtenidos en la presente tesis doctoral.Giner Bosch, V. (2014). Precontrol óptimo. Caracterización, análisis y técnicas de resolución [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/46373TESI

Bi-objective optimization of a multihead weighing process

[EN] A multihead weighing process is a packaging technology that can be of strategic importance to a company, as it can be a key to competitive advantage in the modern food industry. The improvement in the process quality and sensory quality of food packaged in a multihead weighing process investigated in this paper is relevant to industrial engineering. A bi-objective ad hoc algorithm based on explicit enumeration for the packaging processes in multihead weighers with an unequal supply of the product to the weighing hoppers is developed. The algorithm uses an a priori strategy to generate Pareto-optimal solutions and select a subset of hoppers from the set of available ones in each packing operation. The relative importance of both aforementioned objectives is dynamically managed and adjusted. The numerical experiments are provided to illustrate the performance of the proposed algorithm and find the optimum operational conditions for the process.García-Díaz, JC.; Pulido-Rojano, A.; Giner-Bosch, V. (2017). Bi-objective optimization of a multihead weighing process. European J of Industrial Engineering. 11(3):403-423. doi:10.1504/EJIE.2017.084882S40342311

An Evaluation of the environmental factors for supply chain strategy decisions using grey systems and composite indicators

The purpose of this work is to assess the importance of environmental factors in a supply chain with four partners as a preliminary step to select the competitive strategies and objectives. To achieve this purpose, a real case study was carried out in a footwear supply chain, in which two approaches were used: the grey system theory and uncertainty analysis tools for composite indicators. In order to validate both approaches, a seven-phase research methodology was developed and applied to our case study. In addition, the priorization of environmental factors was calculated individually for each partner. The results allow managers to establish the competitive strategy that best suits the prioritization of the most relevant factors and to define the most appropriate objectives where the supply chain should invest its efforts and resources

Impact of Age on Inflammation-Based Scores among Patients Diagnosed with Stage III Non-Small Cell Lung Cancer

[EN] Background: Inflammatory and nutritional indexes are prognostic factors in non-small cell lung cancer (NSCLC). Furthermore, a low grade of chronic inflammation has been described in the older population (inflammaging). We aimed to evaluate the neutrophil-to-lymphocyte ratio (NLR), the Prognostic Nutritional Index (PNI), the advanced lung cancer inflammation index (ALI), the platelet-to-lymphocyte ratio (PLR), and the Glasgow Prognostic Score (GPS) in young and older patients diagnosed with locally advanced NSCLC to determine if significant differences between these groups exist.Methods:We conducted a retrospective study analyzing the impact of age on the NLR, PNI, ALI, PLR, and GPS among patients diagnosed with stage III NSCLC at Hospital Universitario Doctor Peset between 2010 and 2015.Results:We included 124 patients (84 young, 40 older patients). The median hemoglobin level and leukocyte count were lower in the older patients (p= 0.0158 andp= 0.001, respectively). A higher median C-reactive protein level was also found in this group (p= 0.0095). Regarding specific inflammatory indexes, the PNI, comprising inflammatory and nutritional parameters, was lower among the older patients (p= 0.0463). The median NLR, ALI, and PLR were similar in both age groups. Moreover, no differences between the age groups were found in the percentage of patients showing high versus low NLR (cutoff point, 5) or ALI (cutoff point, 18) or in the different GPS groups.Conclusions:The baseline PNI, hemoglobin level, and lymphocyte count were lower among the older patients; furthermore, CRP was higher, possibly, because of a more prominent inflammatory status in older patients with lung cancer. No other immunological or nutritional analytical variables were different between the age groups.Palomar-Abril, V.; Soria-Comes, T.; Tarazona Campos, S.; Martín Ureste, M.; Giner-Bosch, V.; Maestu-Maiques, IC. (2020). Impact of Age on Inflammation-Based Scores among Patients Diagnosed with Stage III Non-Small Cell Lung Cancer. Oncology. 98(8):528-533. https://doi.org/10.1159/000506204S52853398

Impact of SARS-CoV-2 Infection on Patients with Cancer: Retrospective and Transversal Studies in Spanish Population

[EN] Background: Studies of patients with cancer affected by coronavirus disease 2019 (COVID-19) are needed to assess the impact of the disease in this sensitive population, and the influence of different cancer treatments on the COVID-19 infection and seroconversion. Material and Methods: We performed a retrospective analysis of all patients hospitalized with RT-PCR positive for COVID-19 in our region to assess the prevalence of cancer patients and describe their characteristics and evolution (Cohort 1). Concurrently, a transversal study was carried out in patients on active systemic cancer treatment for symptomatology and seroprevalence (IgG/IgM by ELISA-method) against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (Cohort 2). Results: A total of 215 patients (Cohort 1) were admitted to hospital with a confirmed COVID-19 infection between February 28 and April 30, 2020, and 17 died (7.9%). A medical record of cancer was noted in 43 cases (20%), 6 of them required Intensive care unit ICU attention (14%), and 7 died (16%). There were thirty-six patients (83%) who tested IgG/IgM positive for SARS-CoV-2. Patients on immunosuppressive therapies presented a lower ratio of seroconversion (40% vs. 8%; p = 0.02). In Cohort 2, 166 patients were included in a symptoms-survey and tested for SARS-CoV-2. Any type of potential COVID-19-related symptom was referred up to 67.4% of patients (85.9% vs. 48.2% vs. 73.9%, for patients on chemotherapy, immunotherapy and targeted therapies respectively, p < 0.05). The seroprevalence ratio was 1.8% for the whole cohort with no significant differences by patient or treatment characteristics. Conclusion: Patients with cancer present higher risks for hospital needs for COVID-19 infection. The lack of SARS-CoV-2 seroconversion may be a concern for patients on immunosuppressive therapies. Patients receiving systematic therapies relayed a high rate of potentially COVID-19-related symptoms, particularly those receiving chemotherapy. However, the seroconversion rate remains low and in the range of general population.We thank all the patients who consented to this study, and the frontline healthcare professionals who are involved in patients' care during this pandemic. We also thank the technical assistants: M. Portero Hernandez, A. Real Perez, and M. Ocasar Garcia. VGB's research work is partially supported by the Ministerio de Ciencia e Innovacion of Spain under grant No. PID2019-110442GB-I00.Garde-Noguera, J.; Fernández-Murga, ML.; Giner-Bosch, V.; Domínguez-Márquez, V.; García Sánchez, J.; Soler-Cataluña, JJ.; López Chuliá, F.... (2020). Impact of SARS-CoV-2 Infection on Patients with Cancer: Retrospective and Transversal Studies in Spanish Population. Cancers. 12(12):1-11. https://doi.org/10.3390/cancers12123513S1111212Munster, V. J., Koopmans, M., van Doremalen, N., van Riel, D., & de Wit, E. (2020). A Novel Coronavirus Emerging in China — Key Questions for Impact Assessment. New England Journal of Medicine, 382(8), 692-694. doi:10.1056/nejmp2000929Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineeringhttps://coronavirus.jhu.edu/map.htmlInforme Sobre la Situación COVID-19 en España a 6 April 2020. Equipo COVID-19. RENAVE. CNE. CNM (ISCIII). Informe COVID-19 nº21https://covid19.isciii.es/Report 13: Estimating the Number of Infections and the Impact of Non-Pharmaceutical Interventions on COVID-19 in 11 European Countrieshttps://spiral.imperial.ac.uk:8443/handle/10044/1/77731Rothan, H. A., & Byrareddy, S. N. (2020). The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. Journal of Autoimmunity, 109, 102433. doi:10.1016/j.jaut.2020.102433Liang, W., Guan, W., Chen, R., Wang, W., Li, J., Xu, K., … He, J. (2020). Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. The Lancet Oncology, 21(3), 335-337. doi:10.1016/s1470-2045(20)30096-6Sharpe, A. H., & Pauken, K. E. (2017). The diverse functions of the PD1 inhibitory pathway. Nature Reviews Immunology, 18(3), 153-167. doi:10.1038/nri.2017.108Fisher, R. A. (1922). On the Interpretation of χ 2 from Contingency Tables, and the Calculation of P. Journal of the Royal Statistical Society, 85(1), 87. doi:10.2307/2340521Mehta, C. R., & Patel, N. R. (1983). A Network Algorithm for Performing Fisher’s Exact Test in r × c Contingency Tables. Journal of the American Statistical Association, 78(382), 427. doi:10.2307/2288652Wilcoxon, F. (1945). Individual Comparisons by Ranking Methods. Biometrics Bulletin, 1(6), 80. doi:10.2307/3001968Kuderer, N. M., Choueiri, T. K., Shah, D. P., Shyr, Y., Rubinstein, S. M., Rivera, D. R., … de Lima Lopes, G. (2020). Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. The Lancet, 395(10241), 1907-1918. doi:10.1016/s0140-6736(20)31187-9Zhang, L., Zhu, F., Xie, L., Wang, C., Wang, J., Chen, R., … Zhou, M. (2020). Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China. Annals of Oncology, 31(7), 894-901. doi:10.1016/j.annonc.2020.03.296Winter, A. K., & Hegde, S. T. (2020). The important role of serology for COVID-19 control. The Lancet Infectious Diseases, 20(7), 758-759. doi:10.1016/s1473-3099(20)30322-4Venkatesulu, B. P., Thoguluva Chandrasekar, V., Giridhar, P., Advani, P., Sharma, A., Hsieh, C. E., … Krishnan, S. (2020). A systematic review and meta-analysis of cancer patients affected by a novel coronavirus. doi:10.1101/2020.05.27.20115303Van Assen, S., Holvast, A., Benne, C. A., Posthumus, M. D., van Leeuwen, M. A., Voskuyl, A. E., … Bijl, M. (2010). Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab. Arthritis & Rheumatism, 62(1), 75-81. doi:10.1002/art.25033Rousseau, B., Loulergue, P., Mir, O., Krivine, A., Kotti, S., Viel, E., … Tournigand, C. (2012). Immunogenicity and safety of the influenza A H1N1v 2009 vaccine in cancer patients treated with cytotoxic chemotherapy and/or targeted therapy: the VACANCE study. Annals of Oncology, 23(2), 450-457. doi:10.1093/annonc/mdr141Di Cosimo, S., Malfettone, A., Pérez-García, J. M., Llombart-Cussac, A., Miceli, R., Curigliano, G., & Cortés, J. (2020). Immune checkpoint inhibitors: a physiology-driven approach to the treatment of coronavirus disease 2019. European Journal of Cancer, 135, 62-65. doi:10.1016/j.ejca.2020.05.026Bersanelli, M., Scala, S., Affanni, P., Veronesi, L., Colucci, M. E., Banna, G. L., … Liotta, F. (2020). Immunological insights on influenza infection and vaccination during immune checkpoint blockade in cancer patients. Immunotherapy, 12(2), 105-110. doi:10.2217/imt-2019-0200Pollán, M., Pérez-Gómez, B., Pastor-Barriuso, R., Oteo, J., Hernán, M. A., Pérez-Olmeda, M., … Fernández de Larrea, N. (2020). Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. The Lancet, 396(10250), 535-544. doi:10.1016/s0140-6736(20)31483-5Choe, P. G., Perera, R. A. P. M., Park, W. B., Song, K.-H., Bang, J. H., Kim, E. S., … Oh, M. (2017). MERS-CoV Antibody Responses 1 Year after Symptom Onset, South Korea, 2015. Emerging Infectious Diseases, 23(7), 1079-1084. doi:10.3201/eid2307.170310Cao, W.-C., Liu, W., Zhang, P.-H., Zhang, F., & Richardus, J. H. (2007). Disappearance of Antibodies to SARS-Associated Coronavirus after Recovery. New England Journal of Medicine, 357(11), 1162-1163. doi:10.1056/nejmc070348Wu, L.-P., Wang, N.-C., Chang, Y.-H., Tian, X.-Y., Na, D.-Y., Zhang, L.-Y., … Liang, G.-D. (2007). Duration of Antibody Responses after Severe Acute Respiratory Syndrome. Emerging Infectious Diseases, 13(10), 1562-1564. doi:10.3201/eid1310.070576Kissler, S. M., Tedijanto, C., Goldstein, E., Grad, Y. H., & Lipsitch, M. (2020). Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period. Science, 368(6493), 860-868. doi:10.1126/science.abb579

Classification Models for Predicting a Patient Clinical Status: Discussion on the Case of Chemotherapy-induced Neutropenia Duration

San Matías Izquierdo, S.; Clemente-Císcar, M.; Giner-Bosch, V. (2011). Classification Models for Predicting a Patient Clinical Status: Discussion on the Case of Chemotherapy-induced Neutropenia Duration. Treatment Strategies. Oncology. 2(2):124-127. http://hdl.handle.net/10251/114248S1241272

Sobre el uso del control estadístico de procesos en la monitorización de la mortalidad: una aplicación a países europeos

“Estadística Española”: Número especial de análisis de la mortalidad, Tercer cuatrimestre de 2016[EN] The evolution of mortality is a key global concern from both an economic and social point of view. In particular, being able to detect and predict changes in mortality compared to its expected behaviour as accurately as possible is a desirable goal. In this context, the standardized mortality ratio (SMR) is commonly used in order to measure the mortality of a country with regard to its neighbouring countries at a given moment in time. In this work, we address the study of the evolution of the SMR of a country over time, modelled as a time series. The joint use of time series and statistical process control (SPC) techniques to model and monitor the behaviour of the SMR is explored. Both approaches are relevant and complementary. On one hand, time series are an appropriate tool to study and characterize the evolution of SMR over time and to forecast it. On the other hand, SPC permits detection of significant changes in the trend of the variable being monitored. More precisely, we suggest monitoring the residuals of the fitted time series model using control charts. We present and discuss the results of applying our proposal to mortality data for European countries in a 20-year period. These results show the relevance of our approach and delineate our next research steps. Finally, the use of other approaches combining time series and SPC techniques is also outlined.[ES] La evolución de la mortalidad es un asunto de interés global tanto desde un punto de vista económico como social. En concreto, un objetivo deseable es ser capaces de detectar y predecir cambios en la mortalidad en comparación con su comportamiento esperado de manera tan precisa como sea posible. En este contexto, la tasa de mortalidad estandarizada (SMR) es usada normalmente para medir la mortalidad de un país en relación a sus países vecinos en un momento dado del tiempo. En este trabajo abordamos el estudio de la evolución de la SMR de un país a lo largo del tiempo, modelada como una serie temporal. Se explorará el uso conjunto de técnicas de series temporales y control estadístico de procesos (SPC) para monitorizar el comportamiento de la SMR. Ambos enfoques son pertinentes y complementarios. Por un lado, las series temporales son una herramienta adecuada para estudiar y caracterizar la evolución de la SMR a lo largo del tiempo y realizar previsiones sobre él. Por otro lado, el SPC permite detectar cambios significativos en la tendencia de la variable objeto de monitorización. En concreto, se propone monitorizar los residuos del modelo ajustado de series temporales mediante gráficos de control. Presentamos y discutimos los resultados de aplicar nuestra propuesta a datos de mortalidad de países europeos correspondientes a un periodo de 20 años. Dichos resultados muestran la relevancia de nuestro enfoque y sugieren futuros pasos de investigación. Finalmente, se plantea el uso de otros enfoques que combinen técnicas de series temporales y SPC.This work was supported by a grant from Ministerio de Economía y Competitividad (MTM2013-45381-P)Giner Bosch, V.; Cabrerizo Cabanos, MM.; Debón Aucejo, AM. (2016). On the use of Statistical Process Control in Monitoring Mortality. An Application to European Countries. Estadística Española. 58(191):265-275. http://hdl.handle.net/10251/81423S2652755819

Optimal design of pre-control plans

Abstract Pre-control is a quality tool for quick set-up approvals, especially used in short-run processes. It is based on specifications instead of on the natural variability of the process and uses cumulative counts in order to yield a conclusion. Its main drawbacks are a high false alarm rate and a low power to detect process deviations, under certain circumstances. These issues can be addressed by making the technique more flexible, as shown in previous works. In this paper, we introduce a Mathematical Programming approach in order to optimally determine the value of the pre-control parameters, so that it can meet the user&apos;s requirements while minimizing the sample size of the technique. We propose and develop a mathematical model for optimal pre-control and perform some numerical experiments in order to show its effectiveness

Phase II Trial of Oxaliplatin and Capecitabine After Progression to First-Line Chemotherapy in Androgen-Independent Prostate Cancer Patients

[EN] Introduction: Docetaxel plus prednisone is the current standard of care in first-line chemotherapy for metastatic hormone-refractory prostate cancer. However, there is no agent proven as effective after progression to standard docetaxel-based therapy. Platins and capecitabine have shown activity in this setting. Patients and Methods: A total of 14 patients were included in this prospective, single-center trial. All patients had progressed to first-line docetaxel-based treatment. Patients received oxaliplatin 100 mg/sqm on D1 and capecitabine 1000 mg/sqm/bid on days 1 to 14 every 21 days. Results: Median number of cycles was 3. No unexpected toxicity was observed. Only grade 3 toxicity reported was grade 3 anemia. Of the 14 patients, 3 presented grade 2 neuropathy which was spontaneously resolved. Prostate-specific antigenresponse rate was 57%, with a median time to progression of 14.5 weeks, and overall survival of 24 weeks. Conclusions: In the second-line setting, after receiving docetaxel-based chemotherapy, the combination of oxaliplatin and capecitabine offers promising activity with an excellent safety profile.Gasent Blesa, JM.; Giner Marco, V.; Giner-Bosch, V.; Cerezuela Fuentes, P.; Alberola Candel, V. (2011). Phase II Trial of Oxaliplatin and Capecitabine After Progression to First-Line Chemotherapy in Androgen-Independent Prostate Cancer Patients. American Journal of Clinical Oncology. 34(2):1-5. https://doi.org/10.1097/COC.0b013e3181d6b453S1534