Numerical approaches to model and monitor geomechanical reservoir integrity

The emergence of new ideas to obtain energy from the earth subsurface and to store radioactive waste on it impels us to further investigate the response of geological media to forces and temperature variations. For instance, injection of water into wells at high pressures to create fractures and increase permeability of rocks is a widely employed technique to enhance geothermal systems or gas reservoirs. Therefore, increasing our understanding about how such actions influence and are affected by the local stress state of the reservoir and how fractures propagate through it is necessary to efficiently develop extraction projects and, hopefully, to avoid undesired side effects. Also, placing nuclear waste in repositories below the surface monitored by acoustic transmission of seismic signals is currently under investigation. Whereby, an optimal knowledge about how the heterogeneity of the medium and its changes are reflected on the seismic waves is necessary for the correct interpretation of the collected signals. The physics involving these geological processes can be approximately expressed in a mathematical way through the laws of physics and the constitutive relationship of materials deriving in a set of partial differential equation whose complexity depends on the adopted physical model and the rheology of materials to be modelled. As, in most cases, the governing equations are not susceptible to analytical solutions, efficient numerical methods and software are required to simulate realistic problems. We present, by a compilation of current theories, a general mathematical model describing the physics of poro-visco-elasto-plastic geological media. Moreover, on the one hand, we present a computational massively-parallel 3D code to model fluid injection and crack propagation in poro-visco-elasto-plastic rheologies. We reproduce existing 2D benchmarks and give some examples of 3D cases. The results show the importance of the initial stress conditions on the development of failure zones and give a generalization of failure patterns generated from a local increase of pore pressure. Furthermore, we perform simulations of hydraulic fracturing for Well KM-8, UK, showing the significant influence of the permeability of rocks and its changes after fracturing on the development of failure areas. On the other hand, we use the wave propagation software Sofi2D to simulate the seismic monitoring of a deep circular backfilled tunnel with the aim of increasing our ability to understand path effects and, therefore, to infer the situation inside a nuclear waste repository over time. We apply our results on the Full-Scale Emplacement Experiment at the Mont Terri underground rock laboratory.Die Entstehung neuer Ideen zur Gewinnung von Energie aus dem Untergrund der Erde und zur Lagerung radioaktiver Abfälle veranlasst uns dazu, die Reaktion geologischer Materialien auf Kraft- und Temperaturschwankungen weiter zu untersuchen. Beispielsweise ist die Injektion von Wasser in Bohrlöchern bei hohen Drücken, um Brüche zu erzeugen und die Permeabilität von Gesteinen zu erhöhen, eine weit verbreitete Technik, um die Förderrate in geothermischen Systemen oder Kohlenwasserstoffspeichern zu verbessern. Daher ist ein besseres Verständnis, wie sich solche Aktionen auf den lokalen Spannungszustand des Reservoirs auswirken und von diesem beeinflusst werden, und die Art und Weise, wie sich Risse durch dieses ausbreiten, notwendig, um solche Projekte effizient zu entwickeln und unerwünschte Nebenwirkungen bestmöglich zu vermeiden. Momentan wird zudem erwogen, Endlager für radioaktiven Abfall mit Hilfe akustischer Übertragung seismischer Signale zu überwachen. Hierfür ist ein optimaler Wissensstand, über den Einfluss der Heterogenität des Materials und wie diese die seismischen Wellen beeinflusst, notwendig, um die gesammelten Signale korrekt zu interpretieren. Die zugrundeliegende Physik der geologischen Prozesse, kann durch die Gesetze der Physik und die konstitutiven Beziehungen der Materialien, die durch einen Satz partieller Differentialgleichungen abgeleitet werden, angenähert werden. Jedoch hängt deren Komplexität stark von dem verwendeten physikalischen Modell und der Rheologie der zu modellierenden Materialien ab. Da die maßgebenden Gleichungen in den meisten Fällen nicht analytisch lösbar sind, sind effiziente numerische Methoden und Software erforderlich, um die genannten Probleme realitätsnah zu simulieren. Durch eine Zusammenfassung aktueller Theorien, präsentieren wir in dieser Arbeit ein allgemeines mathematisches Model, welches die Physik poro-visko-elasto-plastischer geologischer Materialien beschreibt. Zum Einen stellen wir einen neuen, massiv-parallelen 3D Code vor, um Fluid Injektionen und Rissausbreitung in poro-visko-elasto-plastischen Rheologien zu modellieren. Mit Diesem können wir bestehende 2D Benchmark-Tests reproduzieren und einige Beispiele in 3D vorstellen. Die Resultate zeigen den Einfluss der initialen Spannungsbedingungen auf die Entwicklung von Schwächezonen und erlauben eine Generalisierung von, durch lokalen Porendruckanstieg ausgelösten, Schwächemustern. Weiterhin haben wir Simulationen hydraulischer Frakturierung für Well KM-8, UK, durchgeführt, die den signifikanten Einfluss von Gesteinspermeabilität und dessen Änderungen nach der Frakturierung auf die Entwicklung des Versagensbereiches, anzeigen. Zum Anderen nutzen wir die Wellenausbreitungs-Software Sofi2D zur Simulation seismischer Beobachtungen eines tiefen, runden, verfüllten Tunnels, um unser Verständnis von Pfadeffekten zu verbessern und dadurch auf die Situation in Lagern radioaktiven Abfalls rückschließen zu können. Wir wenden unsere Resultate auf das Full- Scale Emplacement Experiment des Mont Terri Untergrund-Felslabors an

Demo 166. Diferente "expansión" de gases y vapores ilustrada con un frasco de Franklin vertical

Se presenta una demostración de aula que muestra que el vapor de un líquido tiene mucha mayor tendencia a expandirse por calentamiento que un gas, y que la presión de vapor es muy sensible a la temperatura porque tiene una dependencia exponencial con esta. Además se muestra que un aumento de temperatura provoca un desplazamiento del equilibrio hacia estados de mayor entropía.A classroom demonstration is presented showing that the vapor of a liquid has a much greater tendency to expand on heating than a gas, and that vapor pressure is very sensitive to temperature because it has an exponential dependence on temperature. Furthermore, it is shown that an increase in temperature causes a displacement of the equilibrium towards states of larger entropy

Efficacy and safety of native versus pegylated Escherichia coli asparaginase for treatment of adults with high-risk, Philadelphia chromosome-negative acute lymphoblastic leukemia

Native or pegylated (PEG) asparaginase (ASP) are commonly used in treatment of acute lymphoblastic leukemia (ALL), but have been scarcely compared in the same trial in adult patients. Native vs. PEG-ASP administered according to availability in each center were prospectively evaluated in adults with high-risk ALL. Ninety-one patients received native ASP and 35 PEG-ASP in induction. No significant differences were observed in complete remission, minimal residual disease levels after induction and after consolidation, disease-free survival, and overall survival. No significant differences in grades 3–4 toxicity were observed in the induction period, although a trend for higher hepatic toxicity was observed in patients receiving PEG-ASP. In this trial the type of ASP did not influence patient response and outcome.Supported in part with the grants PI10/01417 from Fondo de Investigaciones Sanitarias and RD12/0036/0029 from RTICC, Instituto de Salud Carlos III, 2014 SGR225(GRE), CERCA Program, Generalitat de Catalunya, Spain, and a funding from ‘La Caixa’ Foundation

Novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia

A high proportion of patients with acute myeloid leukemia who achieve minimal residual disease (MRD) negative status ultimately relapse because a fraction of pathological clones remains undetected by standard methods. We designed and validated a high-throughput sequencing method for MRD assessment of cell clonotypes with mutations of NPM1, IDH1/2 and/or FLT3-SNVs. For clinical validation, 106 follow-up samples from 63 patients in complete remission were studied by NGS, evaluating the level of mutations detected at diagnosis. The predictive value of MRD status by NGS, multiparameter flow cytometry, or quantitative PCR was determined by survival analysis. The method achieved a sensitivity of 10-4 for SNV mutations and 10-5 for insertions/deletions and could be used in acute myeloid leukemia patients who carry any mutation (86% in our diagnosis data set). NGS-determined MRD positive status was associated with lower disease-free survival (hazard ratio [HR] 3.4, p=0.005) and lower overall survival (HR 4.2, p<0.001). Multivariate analysis showed that MRD positive status by NGS was an independent factor associated with risk of death (HR 4.54, p =0.005) and the only independent factor conferring risk of relapse (HR 3.76, p =0.012). This NGS based method simplifies and standardizes MRD evaluation, with high applicability in acute myeloid leukemia. It also improves upon flow cytometry and quantitative PCR to predict acute myeloid leukemia outcome and could be incorporated in clinical settings and clinical trials.This study was supported by the Subdirección General de Investigación Sanitaria (Instituto de Salud Carlos III, Spain) grants PI13/02387 and PI16/01530, and the CRIS against Cancer foundation grant 2014/0120. M.L. holds a postdoctoral fellowship of the Spanish Ministry of Economy and Competitiveness (FPDI-2013-16409). P.R.P. holds a postdoctoral fellowship of the Spanish of Instituto de Salud Carlos III: Contrato Predoctoral de Formación en Investigación en Salud i-PFIS (IFI 14/00008).S

Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome–negative adult lymphoblastic leukemia

The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome–negative (Ph−) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph− adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation were assigned to receive delayed consolidation and maintenance therapy up to 2 years in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to-treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95% confidence interval) cumulative incidence of relapse (CIR), overall survival (OS), and event-free survival probabilities for the whole series were 43% ± 7%, 49% ± 7%, and 40% ± 6%, respectively, with CIR and OS rates of 45% ± 8% and 59% ± 9% for patients assigned to chemotherapy and of 40% ± 12% and 38% ± 11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph− adult ALL patients up to 60 years with adequate MRD response after induction and consolidation. Better postremission alternative therapies are especially needed for patients with poor MRD clearance

Outcomes and prognostic factors of adults with refractory or relapsed T-cell acute lymphoblastic leukemia included in measurable residual disease-oriented trials

Despite high complete remission (CR) rates with frontline therapy, relapses are frequent in adults with T-cell acute lymphoblastic leukemia (T-ALL) with limited salvage options. We analyzed the outcomes and prognostic factors for CR to salvage therapy and overall survival (OS) of patients with R/R T-ALL included in two prospective measurable residual disease-oriented trials. Seventy-five patients (70 relapsed, 5 refractory) were identified. Relapses occurred in bone marrow, isolated or combined in 50 patients, and in the central nervous system (CNS; isolated or combined) in 20. Second CR was attained in 30/75 patients (40%). Treatment with FLAG-Ida and isolated CNS relapse were independently associated with a higher CR rate after first salvage therapy. The median OS was 6.2 (95% confidence interval [CI], 3.9–8.6) months, with a 4-year OS probability of 18% (95% CI, 9%–27%). No differences in survival were observed according to the treatment with hematopoietic stem cell transplantation in patients in CR after first salvage therapy. Multivariable analysis showed a ≥12-month interval between first CR and relapse, CR after first salvage therapy and isolated CNS relapse as favorable prognostic factors for OS with hazard ratios (HR) (95% CI) of 1.931 (1.109–3.362), 2.958 (1.640–5.334), and 2.976 (1.157–7.655), respectively. This study confirms the poor outcomes of adults with R/R T-ALL among whom FLAG-Ida was the best of the rescue therapies evaluated. Late relapse, CR after first rescue therapy and isolated CNS relapse showed prognostic impact on survival. More effective rescue therapies are needed in adults with R/R T-ALL.La Caixa" Foundation and ISCIII, Grant/ Award Number: PI19/01828; Generalitat de Catalunya (GRC), Grant/Award Number: 2017 SGR28

The EU Center of Excellence for Exascale in Solid Earth (ChEESE): Implementation, results, and roadmap for the second phase

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Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Sin / Sense

Sexto desafío por la erradicación de la violencia contra las mujeres del Institut Universitari d’Estudis Feministes i de Gènere «Purificación Escribano» de la Universitat Jaume

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic