Continuum modelling using the discrete element method. theory and implementation in an object-oriented software platform

The Discrete Element Method is a relatively new technique that has nowadays and intense research in the field of numerical methods. In its first conception, the method was designed for simulations of dynamic system of particles where each element is considered to be an independent and non-deformable entity that interacts with other particles by the laws of the contact mechanics and moves following the second Newton’s law. This first approach for the DEM has obtained excellent results for granular media simulations or another discontinuouslike case. The existing challenge nowadays for the DEM is to be able to simulate the behaviour on a continuous media discretized by a mesh of particles ruled by the equations of the DEM. Although there exist more adequate methods to solve the continuous problem as they are the different variants of the Finite Element Method, the DEM is expected to have a better behaviour when the failure of the media occurs; in terms of tracking the evolution of the fracture locally between the elements of the discretization and also the post-fractural behaviour of the material. Nowadays, there are several DEM codes that try to solve this problem although there is no one which can assure an accurate solution applicable universally to any case. The objective of the present work is to develop calculation software for the Discrete Element Method included in the platform for numerical methods KRATOS, which is developed in CIMNE. One of the goals of the so-called DEM-Application is to be able to reproduce a wide set of engineering problems; not only the discrete ones such as the excavation or agroalimentary applications but also to reproduce the continuous media, simulating compression test for concrete or asphalt samples for instance. In addition it is desired that the application permits the coupling with another methods, particularly the Finite Element Method. In order to do this, the present work includes the study of all the advances and ideas that, globally in the numerical method field and particularly in CIMNE, have been discussed to give other approaches and to keep improving and developing the to the Discrete Element Method

Análisis arqueomorfológico y dinámica territorial en el Vallés Oriental (Barcelona) de la Protohistoria s. VI-V a.C.) a la alta Edad Media (s. IX-X)

The area of study, located in the Vallès basin, near the city of Barcelona, has undergone an important urbanization process in the last two decades. This fact restrains the retrieving of archaeological data and the development of archaeological surveys and fieldwalking. In this sense, landscape research in urban or peri-urban areas implies important methodological constraints. However, several reports from rescue excavations are available. They are a very useful source for territorial research. The particular topography of the area must also be taken into account. It is characterized by soft slopes resulting from a differentiated seasonal rainfall. Archaeomorphological analysis has been therefore reconsidered in order to adapt its methods and techniques to this particular environment. This paper presents the results of the digital archaeomorfological analysis which have been correlated with historical and archaeological data in order to allow us to characterize the historical road network and territorial organization from a long-term perspective, together with settlement evolution and landscape dynamics in Roman times. The landscape morphology research has been developed from an intensive work involving photo-interpretation and the study of old maps within a GIS environment. This has been especially important because of major landscape changes in large rural areas. The archaeological data resulting from the research over the last years has also been carefully revised in order to plan the archaeological and archaeomorfological surveys developed in several micro-regional sectors.La investigación sobre el paisaje en zonas urbanas o periurbanas implica importantes limitaciones metodológicas. En el presente estudio, el trabajo se centra en un llano pre-litoral próximo a la ciudad de Barcelona, el Vallès Oriental, profundamente urbanizado en las últimas dos décadas, hecho que condiciona la recuperación de nuevos datos arqueológicos y la implementación de programas de prospección arqueológica. Asimismo, la particular topografía que presenta el llano, caracterizado por unos relieves suaves, ha obligado a adaptar la metodología del análisis arqueomorfológico a este contexto geográfico. El artículo presenta los resultados del análisis arqueomorfológico realizado, que han sido cruzados con la documentación histórica y arqueológica para caracterizar —desde una perspectiva diacrónica— la red viaria, la estructuración territorial y la evolución del poblamiento de esta área y, finalmente, determinar las dinámicas del paisaje en época romana. La investigación sobre la morfología del territorio se ha llevado a cabo a partir de un intenso trabajo de fotointerpretación y análisis de la cartografía histórica en entorno SIG, especialmente útil en un paisaje marcado por las importantes trasformaciones del medio rural. Igualmente, los datos generados en los últimos años por la investigación arqueológica han sido revisados de forma detallada, a fin de contribuir a la planificación de las prospecciones arqueológicas y arqueomorfológicas desarrolladas

A local constitutive model for the discrete element method. Application to geomaterials and concrete

This paper presents a local constitutive model for modelling the linear and non linear behavior of soft and hard cohesive materials with the discrete element method (DEM). We present the results obtained in the analysis with the DEM of cylindrical samples of cement, concrete and shale rock materials under a uniaxial compressive strength (UCS) test, different triaxial tests, a uniaxial strain compaction (USC) test and a brazilian tensile strength (BTS) test. DEM results compare well with the experimental values in all cases

Advances in the DEM and coupled DEM and FEM techniques in non linear solid mechanics

In this chapter we present recent advances in the Discrete Element Method (DEM) and in the coupling of the DEM with the Finite Element Method (FEM) for solving a variety of problems in non linear solid mechanics involving damage, plasticity and multifracture situations

Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia

We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20-27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67-4.31) and improved OS (HR=0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data

A novel gene signature unveils three distinct immune- metabolic rewiring patterns conserved across diverse tumor types and associated with outcomes

Existing immune signatures and tumor mutational burden have only modest predictive capacity for the efficacy of immune check point inhibitors. In this study, we developed an immune-metabolic signature suitable for personalized ICI therapies. A classifier using an immune-metabolic signature (IMMETCOLS) was developed on a training set of 77 metastatic colorectal cancer (mCRC) samples and validated on 4,200 tumors from the TCGA database belonging to 11 types. Here, we reveal that the IMMETCOLS signature classifies tumors into three distinct immune-metabolic clusters. Cluster 1 displays markers of enhanced glycolisis, hexosamine byosinthesis and epithelial-to-mesenchymal transition. On multivariate analysis, cluster 1 tumors were enriched in pro-immune signature but not in immunophenoscore and were associated with the poorest median survival. Its predicted tumor metabolic features suggest an acidic-lactate-rich tumor microenvironment (TME) geared to an immunosuppressive setting, enriched in fibroblasts. Cluster 2 displays features of gluconeogenesis ability, which is needed for glucose-independent survival and preferential use of alternative carbon sources, including glutamine and lipid uptake/β-oxidation. Its metabolic features suggest a hypoxic and hypoglycemic TME, associated with poor tumor-associated antigen presentation. Finally, cluster 3 is highly glycolytic but also has a solid mitochondrial function, with concomitant upregulation of glutamine and essential amino acid transporters and the pentose phosphate pathway leading to glucose exhaustion in the TME and immunosuppression. Together, these findings suggest that the IMMETCOLS signature provides a classifier of tumors from diverse origins, yielding three clusters with distinct immune-metabolic profiles, representing a new predictive tool for patient selection for specific immune-metabolic therapeutic approaches

Endoluminal brachytherapy in the treatment of oesophageal cancer. Technique description, case report and review of the literature.

Endoesophageal brachytherapy is a useful technique for the palliative treatment of dysphagia in advanced oesophageal cancer. This technique offers good results on dysphagia control and quality of life.We report the case of a patient treated with this technique presenting complete response to the dysphagia. We describe endoesophageal brachyterapy technique and we comment on the literature

Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team

The lincRNA HOTAIRM1, located in the HOXA genomic region, is expressed in acute myeloid leukemia, impacts prognosis in patients in the intermediate-risk cytogenetic category, and is associated with a distinctive microRNA signature

Altres ajuts: SDCSD from School of Medicine, University of BarcelonaLong non-coding RNAs (lncRNAs) are deregulated in several tumors, although their role in acute myeloid leukemia (AML) is mostly unknown.We have examined the expression of the lncRNA HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) in 241 AML patients. We have correlated HOTAIRM1 expression with a miRNA expression profile. We have also analyzed the prognostic value of HOTAIRM1 expression in 215 intermediate-risk AML (IR-AML) patients.The lowest expression level was observed in acute promyelocytic leukemia (P < 0.001) and the highest in t(6;9) AML (P = 0.005). In 215 IR-AML patients, high HOTAIRM1 expression was independently associated with shorter overall survival (OR:2.04;P = 0.001), shorter leukemia-free survival (OR:2.56; P < 0.001) and a higher cumulative incidence of relapse (OR:1.67; P = 0.046). Moreover, HOTAIRM1 maintained its independent prognostic value within the favorable molecular subgroup (OR: 3.43; P = 0.009). Interestingly, HOTAIRM1 was overexpressed in NPM1-mutated AML (P < 0.001) and within this group retained its prognostic value (OR: 2.21; P = 0.01). Moreover, HOTAIRM1 expression was associated with a specific 33-microRNA signature that included miR-196b (P < 0.001). miR-196b is located in the HOX genomic region and has previously been reported to have an independent prognostic value in AML. miR-196b and HOTAIRM1 in combination as a prognostic factor can classify patients as high-, intermediate-, or low-risk (5-year OS: 24% vs 42% vs 70%; P = 0.004).Determination of HOTAIRM1 level at diagnosis provided relevant prognostic information in IR-AML and allowed refinement of risk stratification based on common molecular markers. The prognostic information provided by HOTAIRM1 was strengthened when combined with miR-196b expression. Furthermore, HOTAIRM1 correlated with a 33-miRNA signatur