ADAPT: an Automatic Diagnosis of Activity and Processes in auTomation environments

In an automated industrial environment, a large volume of data and signals is available, both from sensors and actuators in machinery and from the interaction with operators and users. Operation diagnosis can have multiple applications from a learning point of view (e.g. staff training) or in terms of process assessment. This work proposes a methodology for implementing an Intelligent System by means of any interactive system connected through OPC UA standard. A digital twin of the process supports configuration and validation, prior to commissioning. Activity is interpreted and diagnosed according to the context in which it occurs. Step order in sequence, step duration and sequence duration are analyzed in a use case based on a PLC-controlled robotic cell in which it is operated both in automatic and manual mode for adjusting a linear table’s positioning

Persona Cooperativa en un contexto de transformación educativa y social

El objetivo del presente artículo es definir y caracterizar el perfil de la denominada “Persona Cooperativa” (PC) dentro de las instituciones educativas, facultades universitarias y empresas vinculadas al ámbito educativo cooperativo y dentro del ecosistema cooperativista del País Vasco. Para alcanzar dicho objetivo se realizó una investigación cualitativa mediante el método de la Teoría Fundamentada. Después de constatar que el concepto PC a analizar no es nuevo, la revisión bibliográfica realizada en las principales bases de datos (WOS, Scopus…) no ha aportado una clara definición ni caracterización del perfil. De este modo, se llevaron a cabo 4 entrevistas semiestructuradas, observaciones panorámicas no participantes (14 sesiones, 30 profesionales) y análisis de documentos internos en 3 de las organizaciones participantes en el estudio. El análisis y la triangulación de datos se ha efectuado mediante el método comparativo constante hasta lograr la saturación teórica. El trabajo de investigación ha permitido, por un lado, situar los valores y actitudes individuales, cooperativos y comunitarios como Categoría Central y, por otro, clasificarlo en tres categorías conceptuales principales: ser autosuficiente, ejercer la cooperación y ser emprendedora socio-comunitaria. Entendemos que este trabajo puede contribuir a establecer las bases para el desarrollo del perfil de PC y su evaluación con la implementación de programas educativos asociados a las dimensiones personales, relacionales y socio-comunitarios que lo definen

Cooperative person in a context of educational and social transformation

Nos gustaría agradecer a la Fundación Gizabidea y a la Fundación ULMA por su respaldo y apoyo al proyecto, y a todas aquellas personas y organizaciones que participaron de una manera u otra en el proyecto de investigación.El objetivo del presente artículo es definir y caracterizar el perfil de la denominada “Persona Cooperativa” (PC) dentro de las instituciones educativas, facultades universitarias y empresas vinculadas al ámbito educativo cooperativo y dentro del ecosistema cooperativista del País Vasco. Para alcanzar dicho objetivo se realizó una investigación cualitativa mediante el método de la Teoría Fundamentada. Después de constatar que el concepto PC a analizar no es nuevo, la revisión bibliográfica realizada en las principales bases de datos (WOS, Scopus…) no ha aportado una clara definición ni caracterización del perfil. De este modo, se llevaron a cabo 4 entrevistas semiestructuradas, observaciones panorámicas no participantes (14 sesiones, 30 profesionales) y análisis de documentos internos en 3 de las organizaciones participantes en el estudio. El análisis y la triangulación de datos se ha efectuado mediante el método comparativo constante hasta lograr la saturación teórica. El trabajo de investigación ha permitido, por un lado, situar los valores y actitudes individuales, cooperativos y comunitarios como Categoría Central y, por otro, clasificarlo en tres categorías conceptuales principales: ser autosuficiente, ejercer la cooperación y ser emprendedora socio-comunitaria. Entendemos que este trabajo puede contribuir a establecer las bases para el desarrollo del perfil de PC y su evaluación con la implementación de programas educativos asociados a las dimensiones personales, relacionales y socio-comunitarios que lo definen.The objective of this article is to define and characterize the profile called “Cooperative Person” (CP) in educational institutions, university faculties and enterprises within the cooperative educational ambit of the cooperativist ecosystem in the Basque Country. To achieve this objective, qualitative research was conducted using Grounded Theory. Although this is not a new concept, the literature review of main databases (WOS, Scopus...) has not provided a clear definition or characterization of the profile. Thus, 4 semi-structured interviews, non participant panoramic observations (14 sessions, 30 professionals) and internal document analysis were carried out in 3 of the organizations participating in the study. Triangulation and analysis of data were performed using the constant comparative method, until theoretical saturation was achieved. The research work has allowed, on the one hand, to place individual, cooperative and community values and attitudes as a central category and, on the other, to classify it into three main conceptual categories: to be self sufficient, to exercise cooperation and to be socio-community entrepreneur. We believe that this work can contribute to establishing the basis for the development of the CP profile and its evaluation, with the implementation of educational programs associated with the personal, relational and socio community dimensions that define it the profile.Escuela de Estudios CooperativosFac. de Ciencias Económicas y EmpresarialesTRUEExcma. Diputación Foral de Guipúzcoapu

Detection of genomic alterations in liquid biopsies from patients with non-small cell lung cancer using FoundationOne Liquid CDx: a cost-effectiveness analysis

ObjectiveLiquid biopsy (LB) is a non-invasive technique to detect genetic alterations by next-generation sequencing (NGS) when tissue biopsy is not available. This study aims to estimate in the Spanish setting, the cost-effectiveness of using FoundationOne Liquid CDx (F1L CDx), a novel blood-derived LB test based on NGS, versus non-molecular diagnosis (non-mDx) in patients with advanced non-small cell lung cancer (NSCLC) in whom tissue sampling is not feasible.MethodsA joint model was developed combining a decision-tree with partitioned survival models to calculate the costs and health outcomes over a lifetime horizon, comparing F1L CDx in LB versus non-mDx. Only direct costs (expressed in of 2023) were included and a 3% discount rate for future costs and effects was considered. Health outcomes were expressed in Life Years (LYs) and Quality-Adjusted Life Years (QALYs). Utilities and treatment efficacy were obtained from the literature. An expert panel of 11 Spanish oncologists determined the treatment allocation and validated all model inputs and assumptions. Several sensitivity analyses were performed to assess the robustness of the results.ResultsIn a hypothetical cohort of 1,000 patients, LB using F1L CDx would detect 386 alterations, so those patients could be treated with targeted therapies or enrolled in clinical trials. Cost-effectiveness results showed that F1L CDx provides greater effectiveness than non-mDx (+383.95 LYs and +305.94 QALYs), with an additional cost of 2,898,308. The incremental cost-utility ratio was 9,473/QALY gained. The probabilistic sensitivity analysis confirmed the robustness of the cost-effectiveness results.LimitationsVarious limitations inherent to cost-effectiveness analyses were described.ConclusionLB with F1L CDx test is a cost-effective strategy in Spain for patients with advanced NSCLC without tissue sample available for molecular diagnosis, improving the personalized treatment of these patients

External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma: data from the AGAMENON-SEOM registry

Background: Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer patients based on the ToGA trial. Despite the lack of phase III trials, many clinicians administer trastuzumab with alternative regimens. One meta-analysis suggests that substituting cisplatin for oxaliplatin might lead to greater efficacy and less toxicity. Methods: 594 patients with HER2-positive gastroesophageal adenocarcinoma were recruited from the AGAMENON-SEOM registry. The objective was to evaluate the external validity of clinical trials with chemotherapy and trastuzumab. Results: The regimens used in at least 5% of the patients were XP (27%), oxaliplatin and capecitabine (CAPOX) (26%), oxaliplatin and 5-fluorouracil (FOLFOX) (14%), FP (14%), triplet with anthracycline/docetaxel (7%), and carboplatin-FU (5%). Median exposure to trastuzumab was longer with FOLFOX (11.4 months, 95% CI, 9.1-21.0) versus ToGA regimens (7.5, 6.4-8.5), p < 0.001. Patients with HER2-IHC 3+ cancers had higher response rates than those with IHC 2+/FISH+, odds-ratio 1.97 (95% CI, 1.25-3.09). The results achieved with CAPOX-trastuzumab were comparable to those attained with ToGA regimens. FOLFOX-trastuzumab was superior to ToGA schemes in terms of overall survival (OS), with a greater magnitude of effect in IHC 2+/FISH+ tumors (HR 0.47, 0.24-0.92) compared with IHC 3+ (HR 0.69, 0.49-0.96), and in diffuse (HR 0.37, 0.20-0.69) versus intestinal-type tumors (HR 0.76, 0.54-1.06). Conclusion: We have updated the external validity of clinical trials with trastuzumab in first-line treatment of gastric cancer. Our data confirm the comparable outcomes of ToGA regimens and CAPOX-trastuzumab in clinical practice and point toward a possible benefit of FOLFOX-trastuzumab, contingent on the subtypes typically less sensitive to trastuzumab, to be confirmed in clinical trials

Nomogram-based prediction of survival in patients with advanced oesophagogastric adenocarcinoma receiving first-line chemotherapy: a multicenter prospective study in the era of trastuzumab

Background: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. Methods: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. Results: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5–6.6), 9.4 (95% CI, 8.5–10.6), and 14 months (95% CI, 11.8–16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3–8.1), 12.7 (95% CI, 11.3–14.3), and 18.3 months (95% CI, 14.6–24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591–0.631) and 0.673 (95% CI, 0.636–0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). Conclusions: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design

External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma : data from the AGAMENON-SEOM registry

Background: Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer patients based on the ToGA trial. Despite the lack of phase III trials, many clinicians administer trastuzumab with alternative regimens. One meta-analysis suggests that substituting cisplatin for oxaliplatin might lead to greater efficacy and less toxicity. Methods: 594 patients with HER2-positive gastroesophageal adenocarcinoma were recruited from the AGAMENON-SEOM registry. The objective was to evaluate the external validity of clinical trials with chemotherapy and trastuzumab. Results: The regimens used in at least 5% of the patients were XP (27%), oxaliplatin and capecitabine (CAPOX) (26%), oxaliplatin and 5-fluorouracil (FOLFOX) (14%), FP (14%), triplet with anthracycline/docetaxel (7%), and carboplatin-FU (5%). Median exposure to trastuzumab was longer with FOLFOX (11.4 months, 95% CI, 9.1-21.0) versus ToGA regimens (7.5, 6.4-8.5), p < 0.001. Patients with HER2-IHC 3+ cancers had higher response rates than those with IHC 2+/FISH+, odds-ratio 1.97 (95% CI, 1.25-3.09). The results achieved with CAPOX-trastuzumab were comparable to those attained with ToGA regimens. FOLFOX-trastuzumab was superior to ToGA schemes in terms of overall survival (OS), with a greater magnitude of effect in IHC 2+/FISH+ tumors (HR 0.47, 0.24-0.92) compared with IHC 3+ (HR 0.69, 0.49-0.96), and in diffuse (HR 0.37, 0.20-0.69) versus intestinal-type tumors (HR 0.76, 0.54-1.06). Conclusion: We have updated the external validity of clinical trials with trastuzumab in first-line treatment of gastric cancer. Our data confirm the comparable outcomes of ToGA regimens and CAPOX-trastuzumab in clinical practice and point toward a possible benefit of FOLFOX-trastuzumab, contingent on the subtypes typically less sensitive to trastuzumab, to be confirmed in clinical trials

On the Effect of Triplet or Doublet Chemotherapy in Advanced Gastric Cancer: Results From a National Cancer Registry

Background: There is currently no consensus regarding first-line chemotherapy for patients with advanced gastric cancer (AGC) who are ineligible to receive trastuzumab. The objective of this study was to evaluate the efficacy and tolerance of triplets versus doublets by analyzing a national gastric cancer registry. Patients and Method: Patients with AGC treated with polychemotherapy without associating trastuzumab were included from 2008 through 2016. The effect of triplets versus doublets was compared using 3 methods: Cox proportional hazards regression, propensity score matching (PSM), and coarsened exact matching (CEM). Results: A total of 970 patients were recruited (doublets: n=569; triplets: n=401). In the multivariate Cox model, the use of triplets was associated with better overall survival (OS), with a hazard ratio (HR) of 0.84 (95% CI, 0.72–0.98; P=.035). After PSM, the sample contained 340 pairs. A significant increase in OS, 11.14 months (95% CI, 9.60–12.68) versus 9.60 months (95% CI, 8.44–10.75), was seen in favor of triplets (HR, 0.77; 95% CI, 0.65–0.92; stratified log-rank test, P=.004). The effect appeared to be comparable for anthracycline-based (HR, 0.78; 95% CI, 0.64–0.94) or docetaxel-based triplets (HR, 0.78; 95% CI, 0.60–1.009). The trend was similar after applying the CEM algorithm, with an HR of 0.78 (95% CI, 0.63–0.97; P=.03). Triplet therapy was viable and relative dose intensities exceeded 85%, except for cisplatin in DCX (docetaxel, cisplatin, capecitabine). Triplets had more severe toxicity overall, especially hematologic, hepatic, and mucosal adverse events. Conclusions: With the limitations of a retrospective study that examines a heterogeneous set of chemotherapy regimens, we found that triplets are feasible in daily practice and are associated with a discreet benefit in efficacy at the expense of a moderate increase in toxicity

Lauren subtypes of advanced gastric cancer influence survival and response to chemotherapy: real-world data from the AGAMENON National Cancer Registry.

The choice of chemotherapy in HER2-negative gastric cancer is based on centre's preferences and adverse effects profile. No schedule is currently accepted as standard, nor are there any factors to predict response, other than HER2 status. We seek to evaluate whether Lauren type influences the efficacy of various chemotherapies and on patient overall survival (OS). We have conducted a multicenter study in 31 hospitals. The eligibility criteria include diagnosis of stomach or gastroesophageal junction adenocarcinoma, HER2 negativity, and chemotherapy containing 2-3 drugs. Cox proportional hazards regression adjusted for confounding factors, with tests of 'treatment-by-histology' interaction, was used to estimate treatment effect. Our registry contains 1303 tumours analysable for OS end points and 730 evaluable for overall response rate (ORR). A decrease in ORR was detected in the presence of a diffuse component: odds ratio 0.719 (95% confidence interval (CI), 0.525-0.987), P=0.039. Anthracycline- or docetaxel-containing schedules increased ORR only in the intestinal type. The diffuse type displayed increased mortality with hazard ratio (HR) of 1.201 (95% CI, 1.054-1.368), P=0.0056. Patients receiving chemotherapy with docetaxel exhibited increased OS limited to the intestinal type: HR 0.65 (95% CI, 0.49-0.87), P=0.024, with no increment in OS for the subset having a diffuse component. With respect to progression-free survival (PFS), a significant interaction was seen in the effect of docetaxel-containing schedules, with better PFS limited to the intestinal type subgroup, in the comparison against any other schedule: HR 0.65 (95% CI, 0.50-0.85), P=0.015, and against anthracycline-based regimens: HR 0.64 (95% CI, 0.46-0.88), P=0.046. As a conclusion, in this registry, Lauren classification tumour subtypes predicted survival and responded differently to chemotherapy. Future clinical trials should stratify effect estimations based on histology

Prognostic significance of performing universal HER2 testing in cases of advanced gastric cancer.

Trastuzumab significantly improves overall survival (OS) when added to cisplatin and fluoropyrimidine as a treatment for HER2-positive advanced gastric cancers (AGC). The aim of this study was to evaluate the impact of the gradual implementation of HER2 testing on patient prognosis in a national registry of AGC. This Spanish National Cancer Registry includes cases who were consecutively recruited at 28 centers from January 2008 to January 2016. The effect of missing HER2 status was assessed using stratified Cox proportional hazards (PH) regression. The rate of HER2 testing increased steadily over time, from 58.3 % in 2008 to 92.9 % in 2016. HER2 was positive in 194 tumors (21.3 %). In the stratified Cox PH regression, each 1 % increase in patients who were not tested for HER2 at the institutions was associated with an approximately 0.3 % increase in the risk of death: hazard ratio, 1.0035 (CI 95 %, 1.001-1.005), P = 0.0019. Median OS was significantly lower at institutions with the highest proportions of patients who were not tested for HER2. Patients treated at centers that took longer to implement HER2 testing exhibited worse clinical outcomes. The speed of implementation behaves as a quality-of-care indicator. Reviewed guidelines on HER2 testing should be used to achieve this goal in a timely manner