A Decision Support System (DSS) for the Prediction and Selection of Optimum Operational Parameters in Pressure Die-Casting Processes.

A large number of material and process parameters affect both the part quality and the process performance in pressure die-casting (PDC) processes. The complex relations between most of these variables make PDC process optimisation a difficult issue which has been widely studied for many years. Although there are several analytical and numerical models to optimise certain process parameters, it is difficult to establish a specific operational configuration for PDC machines that ensures the joint optimisation of these variables. Therefore, in this study, some of these optimisation models have been implemented in a Decision Support System (DSS) that allows us to define an operational region that establishes a setup of machine parameters that ensures the manufacture of quality parts. By using this DSS, the user can set the values of the input variables related to the casting material, the die, or the casting machine. Then the corresponding calculations are made by the system and the results are expressed in terms of certain output variables such as the maximum filling time, maximum filling fraction, or the plunger velocity profile among others. The DSS allows the user to estimate the influence between input and output variables and find proper values for the input variables to achieve an optimum operational range. Consequently, improved process performance can be achieved taking into account productivity, part quality, and economic aspects.

Analysis of Tube-to-Tubesheet Welding in Carbon Steel Heat Exchangers of a Double Plate Header Box.

The rear wall of the header box serves as a tubesheet in heat exchangers of double plate header box. Tube-to-tubesheet welding must be performed using orbital Gas Tungsten Arc Welding (GTAW) with a head extension, which is passed through the corresponding hole in the front wall (plugsheet) of the header box, where the welding machine is supported. In this project, the effect of parallelism deviations between the plugsheet and the tubesheet of carbon steel header box is analyzed to evaluate its influence on the quality of the tube-to-tubesheet welding. Welded tube (SA-210 Gr. A1) to tubesheet (SA-516 Gr. 70) coupons are manufactured simulating the parallelism deviations previously analyzed in two double plate header boxes of air-cooled heat exchangers using two different preheating temperatures. Macrographic analysis is performed in order to evaluate the weld penetration (minimum leak path) and length of the weld leg in tube-to-tubesheet joints. The results obtained show important variations in those parameters when the parallelism deviations are equal to or greater than -1 mm over the theoretical distance as well as when the distance approaches +1 mm or more. Finally, the incorporation of dimensional controls prior to the welding process is discussed and the implementation of improvements in orbital GTAW equipment is recommended as an optimal solution for this kind of heat exchangers.

[Improvement of the management of outpatient consultations by a direct automatic citation of interconsultations]. / Mejora de la gestión de las consultas externas hospitalarias mediante la cita automática directa de interconsultas.

OBJECTIVE: The delay caused to provide an appointment and the uncertainty of the expected waiting time, are cause for discontent in the patients. The object of this work was to improve the accessibility to the consultation of specialized attention in our health area, decreasing the average waiting time and reduce the number of claims for this reason. METHODS: To measure the quality of the service provided, 5 criteria were developed and evaluated, by means of a cross section, in December 2015 for all patients pending appointment in the Area. Likewise, the complaints and claims collected during the 6 months prior to this date were quantified. As an intervention, a new circuit was designed and implemented in the interconsultation process, protocolizing a direct and automatic citation system. This system also eliminated patients without an appointment, allowing prioritization in preferred cases. At the end of 2016, a new evaluation was made with the same methodology. For the statistical analysis, Student's t and Chisquare were used. RESULTS: In six months the number of patients without appointment was reduced from 4726 to 0. The average waiting time for external consultations improved from 63 to 44.2 days. Patients waiting more than 50 days increased from 41.5% to 74.8%. The number of complaints and claims due to appointment in external consultations decreased from 161 to 80. CONCLUSIONS: Accessibility has improved by reducing the average waiting time and eliminating the list of patients without an appointment, although the number of patients pending appointments for more than 50 days has increased. The number of complaints and claims has been halved.

OBJETIVO: La demora originada para proporcionar una cita y la incertidumbre del tiempo previsto de espera, son causa de descontento en los pacientes. El objetivo de este trabajo fue mejorar la accesibilidad a la consulta de atención especializada en nuestra área de salud, disminuyendo el tiempo medio de espera y reducir el número de reclamaciones por este motivo. METODOS: Para medir la calidad del servicio prestado, se elaboraron 5 criterios que se evaluaron inicialmente mediante un corte transversal, en diciembre de 2015, en todos los pacientes pendientes de cita en el Área. Así mismo se cuantificaron las quejas y reclamaciones recogidas los 6 meses anteriores a esta fecha. Como intervención, se diseñó e implementó un nuevo circuito en el proceso interconsulta, protocolizando un sistema directo y automático de citación. Este sistema eliminaba además los pacientes sin cita, permitiendo la priorización en los casos preferentes. Al final de 2016 se realizó una nueva medición con la misma metodología. Para el análisis estadístico se han usado la t de Student y la Chi cuadrado. RESULTADOS: En seis meses se redujo el número de pacientes sin cita de 4.726 a 0. El tiempo medio de espera en consultas externas pasó de 63 a 44,2 días. Los pacientes en espera de más de 50 días pasaron del 41,5% al 74,8%. El número de quejas y reclamaciones debidas a cita en consultas externas pasó de 161 a 80. CONCLUSIONES: Ha mejorado la accesibilidad al disminuir el tiempo de espera media y se ha eliminado la lista de pacientes sin cita, si bien ha aumentado el número de pacientes pendientes de cita de más de 50 días. Se ha reducido a la mitad el número de quejas y reclamaciones.

Chemotaxonomy of Gonospermum and related genera.

Aerial parts of Gonospermum fruticosum collected at several locations in the Canary Islands afforded, in addition to known compounds, four sesquiterpene alcohols related to costol and a sesquiterpene lactone, whose structures were established on the basis of their spectroscopic data and chemical transformations. Except for Gonospermum species collected on the island of Tenerife, those collected on the island of El Hierro and, in a previous study those from La Gomera, contain sesquiterpene lactones that can be used as chemotaxonomic markers confirming the inclusion of Gonospermum, Lugoa, and species of Tanacetum endemic to the Canary Islands in a genus that does not support the monophyly of Gonosperminae.

Sesquiterpene lactones from Gonospermum gomerae and G. fruticosum and their cytotoxic activities.

Four new sesquiterpene lactones (1-4) and a new sesquiterpene (5) together with 20 known compounds were isolated from two Gonospermum species (G. gomerae Bolle and G. fruticosum Less). Their structures were determined by analysis of spectroscopic data, including 1D and 2D NMR. The cytotoxicity of several new and known natural and semisynthetic sesquiterpene lactones was also assessed against human myeloid leukemia cell lines (HL-60 and U937), human melanoma cells (SK-MEL-1), and human adenocarcinoma (A549).

Comparison of the results of the treatment of adolescents and young adults with standard-risk acute lymphoblastic leukemia with the Programa Español de Tratamiento en Hematología pediatric-based protocol ALL-96.

PURPOSE: Retrospective studies have shown that adolescents and young adults with acute lymphoblastic leukemia (ALL) treated with pediatric protocols have better outcomes than similarly aged patients treated with adult protocols, but prospective studies comparing adolescents and young adults using pediatric schedules are scarce. The ALL-96 protocol was addressed to compare the toxicity and results of a pediatric-based protocol in adolescents (age 15-18 years) and young adults (age 19-30 years) with standard-risk (SR) ALL. PATIENTS AND METHODS: Adolescents (n = 35) and young adults (n = 46) received a standard five-drug/5-week induction course followed by two cycles of early consolidation, maintenance with monthly reinforcement cycles up to 1 year in continuous complete remission (CR) and 1 year with standard maintenance chemotherapy up to 2 years in CR. RESULTS: Adolescents and young adults were comparable in the main pretreatment ALL characteristics. The CR rate was 98% and. after a median follow-up of 4.2 years, 6-year event-free survival (EFS) and overall survival (OS) were 61% (95% CI, 51% to 72%) and 69% (95% CI, 59% to 79%), respectively, with no differences between adolescents and young adults. The hematologic toxicity in consolidation and reinforcement cycles was higher in young adults than in adolescents. Slow response to induction therapy was the only parameter associated with poor EFS (34% v 67%) and OS (40% v 76%). CONCLUSION: The response to the pediatric ALL-96 protocol was identical in adolescents and young adults despite a slight increase in hematologic toxicity observed in adults. This justifies the age-unrestricted use of pediatric regimens to treat patients with SR ALL.

Comparison of intensive chemotherapy, allogeneic, or autologous stem-cell transplantation as postremission treatment for children with very high risk acute lymphoblastic leukemia: PETHEMA ALL-93 Trial.

PURPOSE: The optimal postremission therapy for children with very high-risk (VHR) acute lymphoblastic leukemia (ALL) is not well established. This randomized trial compared three options of postremission therapy: chemotherapy and allogeneic or autologous stem-cell transplantation (SCT). PATIENTS AND METHODS: All 106 VHR-ALL patients received induction with five drugs followed by intensification with three cycles of chemotherapy. Patients in complete remission (CR) with an HLA-identical family donor were assigned to allogeneic SCT (n = 24) and the remaining were randomly assigned to autologous SCT (n = 38) or to delayed intensification followed by maintenance chemotherapy up to 2 years in CR (n = 38). RESULTS: Overall, 100 patients achieved CR (94%). With a median follow-up of 6.5 years, 5-year disease-free survival (DFS) and overall survival (OS) probabilities were 45% (95% CI, 37% to 54%) and 48% (95% CI, 40% to 57%), respectively. The three groups were comparable in the main pretreatment ALL characteristics. Intention-to-treat analysis showed no differences for donor versus no donor in DFS (45%; 95% CI, 27% to 65% v 45%; 95% CI, 37% to 55%) and OS (48%; 95% CI, 30% to 67% v 51%; 95% CI, 43% to 61%), as well as for autologous SCT versus chemotherapy comparisons (DFS: 44%; 95% CI, 29% to 60% v 46%; 95% CI, 32% to 62%; OS: 45%; 95% CI, 31% to 62% v 57%; 95% CI, 43% to 73%). No differences were found within the different subgroups of ALL and neither were differences observed when the analysis was made by treatment actually performed. CONCLUSION: This study failed to prove that, when a family donor is available, allogeneic SCT produces a better outcome than autologous SCT or chemotherapy in children with VHR-ALL.

Comparison of intensive chemotherapy, allogeneic or autologous stem cell transplantation as post-remission treatment for adult patients with high-risk acute lymphoblastic leukemia. Results of the PETHEMA ALL-93 trial.

BACKGROUND AND OBJECTIVES: The optimal post-remission therapy for adults with high-risk acute lymphoblastic leukemia (ALL) is not well established. This multicenter randomized trial by the Spanish PETHEMA Group was addressed to compare three options of post-remission therapy in adults with high-risk ALL: chemotherapy, allogeneic stem cell transplantation (SCT) and autologous SCT. DESIGN AND METHODS: A total of 222 valid high-risk ALL patients entered the trial. All received a standard five-drug/five-week induction course. Patients in complete remission with an HLA-identical family donor were assigned to allogeneic SCT (n=84) and the remaining were randomized to autologous SCT (n=50) or to delayed intensification followed by maintenance chemotherapy up to 2 years in complete remission (n=48). RESULTS: Overall, 183 patients achieved complete remission (82%). With a median follow-up of 70 months, the median disease-free survival and overall survival were 17 and 23 months, respectively. The 5-year disease-free survival and overall survival were 35% (95% CI, 30%-41%) and 34% (95% CI, 28%-39%), respectively. Patients allocated to the chemotherapy, allogeneic and autologous SCT were comparable in the main pre-treatment ALL characteristics and the rate of response to therapy. Intention-to-treat analysis showed no differences between patients according to whether they had or did not have a donor in disease-free survival (39%, 95% CI 30-48% vs. 33%, 95% CI 23-41%) and overall survival (44%, 95% CI 35-52% vs. 35%, 95% CI 25-44%), as well as for autologous SCT vs. chemotherapy comparisons (disease-free survival: 40%, 95% CI 28-52% vs. 51%, 95% CI 37-67%; overall survival: 43%, 95% CI 29-58% vs. 52%, 95% CI 39-65%). No differences were observed when the analysis was made on the basis of the treatment actually performed. INTERPRETATION AND CONCLUSIONS: This study failed to prove that, when a family donor is available, allogeneic SCT produces a better outcome than autologous SCT or chemotherapy in adults with high-risk ALL.

[Prevalence and prognostic significance of myeloid markers in adults with high-risk acute lymphoblastic leukemia]. / Prevalencia y significado pronóstico de los marcadores mieloides en adultos con leucemia aguda linfoblástica de alto riesgo.

BACKGROUND AND OBJECTIVE: The prognostic value of myeloid antigen expression in adult acute lymphoblastic leukemia (ALL) is controversial. The objective of this study was to evaluate the frequency and prognostic significance of myeloid antigen expression in adults with high risk ALL. PATIENTS AND METHOD: Between June 1993 and July 2002, 222 adults patients with high-risk ALL were treated according to the PETHEMA LAL 93 protocol. The frequency of myeloid antigen expression, its association with other clinical and biologic variables and the prognostic significance in terms of complete remission (CR) rate, event free survival (EFS) and overall survival (OS) were analyzed. RESULTS: Myeloid antigen expression was present in 96 out of 222 patients (43%). No association was observed between myeloid antigen expression and the main clinical and biologic characteristics of ALL. Response to treatment was slower in patients expressing myeloid antigens, but no differences were found in CR achievement, EFS or OS. The probability of EFS at 10 years for ALL patients without and with myeloid antigen expression was 35% and 34%, respectively, while the probability of OS at 10 years was 30% and 33%, respectively. This absence of differences in EFS and OS probabilities was also observed when only slow responding patients were analyzed. CONCLUSIONS: In this study, myeloid antigen expression did not have prognostic influence in adult patients with high risk ALL.

Lack of influence of human immunodeficiency virus infection status in the response to therapy and survival of adult patients with mature B-cell lymphoma or leukemia. Results of the PETHEMA-LAL3/97 study.

BACKGROUND AND OBJECTIVES: Short, intensive multiagent chemotherapy has resulted in significant progress in Burkitt's lymphoma and leukemia. A protocol was designed to treat all adult patients with mature B-cell lymphoma or leukemia with the aims of comparing the response to therapy and survival with regards to their HIV infection status. DESIGN AND METHODS: Fifty-three adult patients with advanced stage Burkitt's lymphoma or Burkitt's leukemia were treated. Response to therapy, survival and toxicity were evaluated according to their HIV infection status. RESULTS: The median age of the patients was 53 years (range 15-74). There were no differences in CR rates between HIV-negative (77%) and HIV-positive patients (71%). Only age > 60 years was associated with a lower CR rate (OR 0.18, 95%CI 0.04-0.81, p=0.026). The 2-year overall survival (OS) probability was 51% (95%CI, 38%-64%) for the 53 patients. The OS of HIV-negative and HIV-positive patients did not significantly differ. Only age > 60 years was associated with a shorter OS (OR 5.1, 95%CI 2.0-12.7, p=0.001). The 2-year disease free survival (DFS) for the 40 patients achieving CR was 60% (95%CI, 45%-75%). Age > 60 years was the only identified factor associated with a shorter DFS (OR 5.2, 95%CI 1.4-20, p=0.015). INTERPRETATION AND CONCLUSIONS: This study confirms the effectiveness of intensive strategies in adult patients with advanced stage Burkitt's lymphoma or leukemia. It also shows the feasibility of these strategies in individuals with HIV infection with comparable results. Advanced age proved to be the main adverse prognostic factor for response to therapy and survival.

Prognostic value of karyotypic analysis in children and adults with high-risk acute lymphoblastic leukemia included in the PETHEMA ALL-93 trial.

BACKGROUND AND OBJECTIVES: Cytogenetic analysis is one of the most reliable prognostic factors in acute lymphoblastic leukemia. The objective of this study was to analyze the prognostic value of cytogenetic analysis in children and adults with high-risk acute lymphoblastic leukemia (HR-ALL) included in a prospective multicenter trial. DESIGN AND METHODS: One hundred and thirty patients (44 children and 86 adults) with HR-ALL included in the PETHEMA ALL-93 trial had an adequate cytogenetic study after review. Cytogenetic subgroups were established according to the cancer and acute leukemia group B criteria (unfavorable: 11q23, t(9;22), -7 and +8; normal; miscellaneous: the remaining chromosome abnormalities) and their main clinicobiological features were compared. Univariable and multivariable analyses for complete remission (CR) attainment, event-free survival (EFS) and overall survival (OS) were performed. RESULTS: The mean SD age was 26 14 years. Two were infants (<1 year), 42 were children and 86 adults (19-50 years). The cytogenetic study was normal in 44 (34%) cases. The most frequent chromosomal rearrangement was t(9;22)(q34;q11) (34 cases, 26%, 30 adults), followed by 11q23 (12 cases, 9% -8 children-, including t(4;11)(q21;q23) in 8, 7 children). Patients with t(9;22) were older than the remaining cases, whereas those with 11q23 rearrangements were younger and had higher WBC counts. Multivariable analyses showed two associated factors in adults with a lower frequency of CR and a shorter EFS and OS: t(9;22) and slow response to therapy (assessed by a percentage of blast cells higher than 10% in bone marrow study on day 14). For children with very high-risk ALL, only slow response to therapy (assessed by the presence of blast cells in peripheral blood on day 8) was associated with a negative impact on CR, EFS and OS. INTERPRETATION AND CONCLUSIONS: In adult patients with high-risk acute lymphoblastic leukemia included in the PETHEMA ALL-93 protocol, cytogenetic analysis at diagnosis is a useful independent prognostic marker. The poorest prognosis for patients with t(9;22) justifies the development of specific treatments for these patients. In this small subgroup of children with very high-risk ALL no cytogenetic characteristics was found to influence the results of therapy, slow response to therapy being the only prognostic factor.