Symmetries and Invariants for Non-Hermitian Hamiltonians

We discuss Hamiltonian symmetries and invariants for quantum systems driven by non-Hermitian Hamiltonians. For time-independent Hermitian Hamiltonians, a unitary or antiunitary transformation AHA that leaves the Hamiltonian H unchanged represents a symmetry of the Hamiltonian, which implies the commutativity [H, A] = 0 and, if A is linear and time-independent, a conservation law, namely the invariance of expectation values of A. For non-Hermitian Hamiltonians, H comes into play as a distinct operator that complements H in generalized unitarity relations. The above description of symmetries has to be extended to include also A-pseudohermiticity relations of the form AH = H A. A superoperator formulation of Hamiltonian symmetries is provided and exemplified for Hamiltonians of a particle moving in one-dimension considering the set of A operators that form Klein's 4-group: parity, time-reversal, parity&time-reversal, and unity. The link between symmetry and conservation laws is discussed and shown to be richer and subtler for non-Hermitian than for Hermitian Hamiltonians.This research was funded by Basque Country Government (grant number IT986-16), MINECO/FEDER, UE (grant number FIS2015-67161-P). M.A. Simon acknowledges support by the Basque Government predoctoral program (grant number PRE-2017-2-0051)

Fundamento y diseño de un proyecto de evaluación de la integración educativa de los niños con necesidades especiales por su deficiencia visual

Este artículo pretende dar a conocer una investigación de evaluación de la educación integrada con niños ciegos y deficientes visuales en España que se está realizando por la O.N.C.E. con un grupo de profesores de la Universidad Autónoma de Madrid. En él se hace un resumen de los objetivos y naturaleza de la investigación evaluativa emprendida, valorativa, iluminativa y formativa, y un análisis del diseño, variables y metodología usada en la investigaciónThis article feports a research work on the evaluation of educational integration with blind and visually handicapped children in Spain. The research is being conducted by the O.N.C.E. in collaboration with a group o teachers of the Universidad Autónoma de Madrid. It outlines the objectives and nature of the evaluative study undertaken (valuative, instructive and formative) and analyzes the design, thé variables and the methodology used in the stud

Does an early mobilization and immediate home-based self-therapy exercise program displace proximal humeral fractures in conservative treatment? Observational study

Background: Nonoperative management of proximal humeral fractures (PHFs) is the most common treatment, but its functional outcome may improve with early mobilization. In frail osteoporotic patients, quick recovery of prefracture independency is mandatory. This study assessed fracture displacement in PHFs managed with conservative treatment after early mobilization and a home-based self-exercise program. Methods: We retrospectively analyzed the radiologic displacement of fracture fragments of PHFs treated conservatively with early mobilization and a home-based self-exercise program. Results: Included were 99 patients with 26 one-part, 32 two-part, 32 three-part, and 9 four-part PHFs managed conservatively, followed by early mobilization and a home-based self-exercise program. In the x-ray examinations, the head displaced from varus into valgus 55° ± 23° to 42° ± 22°, in the normal range of anatomic values. The medial hinge displaced from medial to the diaphysis (+1 ± 6 mm) to lateral to the head (-0.6 ± 6 mm). The greater tuberosity displaced cranially from -1 ± 7 mm to 2 ± 5 mm. The Constant score at the 1-year follow-up was 79.69 ± 16.3. Discussion and conclusions: The home-based self-exercise program for conservative treatment of PHFs displaces the head-diaphysis angle and the medial hinge toward anatomic reduction, but there is a risk of greater tuberosity cranial displacement. Functional results are fairly good, allowing frail patients to keep on with their independency and life style. Because a large number of patients might need further physiotherapy, the quality of the home-based self-exercises should be supervised. Keywords: Proximal humeral fracture; conservative treatment; displaced; early mobilization; home-based exercise; osteoporotic; physiotherapy

Integrated flow cytometry and sequencing to reconstruct evolutionary patterns from dysplasia to acute myeloid leukemia

Clonal evolution in acute myeloid leukemia (AML) originates long before diagnosis and is a dynamic process that may affect survival. However, it remains uninvestigated during routine diagnostic workups. We hypothesized that the mutational status of bone marrow dysplastic cells and leukemic blasts, analyzed at the onset of AML using integrated multidimensional flow cytometry (MFC) immunophenotyping and fluorescence-activated cell sorting (FACS) with next-generation sequencing (NGS), could reconstruct leukemogenesis. Dysplastic cells were detected by MFC in 285 of 348 (82%) newly diagnosed patients with AML. Presence of dysplasia according to MFC and World Health Organization criteria had no prognostic value in older adults. NGS of dysplastic cells and blasts isolated at diagnosis identified 3 evolutionary patterns: stable (n = 12 of 21), branching (n = 4 of 21), and clonal evolution (n = 5 of 21). In patients achieving complete response (CR), integrated MFC and FACS with NGS showed persistent measurable residual disease (MRD) in phenotypically normal cell types, as well as the acquisition of genetic traits associated with treatment resistance. Furthermore, whole-exome sequencing of dysplastic and leukemic cells at diagnosis and of MRD uncovered different clonal involvement in dysplastic myelo-erythropoiesis, leukemic transformation, and chemoresistance. Altogether, we showed that it is possible to reconstruct leukemogenesis in ∼80% of patients with newly diagnosed AML, using techniques other than single-cell multiomics.This work was supported by grants from the Área de Oncología del Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red (CIBER-ONC) (CB16/12/00369, CB16/12/00233, CB16/12/00489, and CB16/12/00284), Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS numbers PI16/01661, PI16/00517, and PI19/01518), and the Plan de Investigación de la Universidad de Navarra (PIUNA 2014-18). This work was supported internationally by the Cancer Research UK, FCAECC, and AIRC under the Accelerator Award Program (EDITOR)

Enseñanza de la Lingüística desde una perspectiva trilingüe

El presente trabajo recoge la investigación llevada a cabo en la asignatura “Lingüística General II” (31721), 6 ECTS de formación básica del segundo curso de los grados en lenguas modernas (español, inglés, francés, catalán y árabe) que se ofertan en la Facultad de Filosofía y Letras de la Universidad de Alicante (UA). La asignatura, impartida en inglés, valenciano y castellano desde hace cuatro años a unos doscientos estudiantes, combina la formación teórica con actividades prácticas a partes iguales. Continuando con la labor que iniciamos el curso pasado, la red de investigación creada para trabajar sobre esta materia, central para el área de Lingüística General de la UA, presenta aquí tanto el diseño y revisión de prácticas en las tres lenguas vehiculares como la evaluación que el alumnado realiza sobre el desarrollo de estas actividades en el aula, a fin de introducir las mejoras necesarias

Proyecto docente innovador desarrollado en Grado en Ingeniería en Diseño Industrial y Desarrollo de Producto para la consecución de un Prototipo Funcional mediante trabajo en equipo

[ES] Se propone un método docente innovador para fomentar el trabajo en equipo a la vez que se adquiere habilidades en nuevas tecnologías de interés para el ingeniero de diseño industrial y del producto. Inicialmente a los estudiantes se les propone realizar una investigación siguiendo una metodología de aprendizaje inverso, invitándoles a analizar experimentalmente cómo funcionan muchos de los aparatos tecnológicos que los rodean. Se trata de redescubrir la curiosidad innata de aprendizaje desmontando un producto para ver de qué está hecho y qué mecanismos lo hacen funcionar. Además, durante estas jornadas teórico-prácticas se les muestra materiales, instrumentos y metodologías para realizar prototipos funcionales, como son materiales luminiscentes, escáneres 3D, arcillas de modelado y tecnologías novedosas de código abierto dedicadas al prototipado. Las posteriores evaluaciones y la experiencia adquirida con esta metodología demuestra que la metodología implantada consigue favorecer el trabajo en equipo a la vez que se recupera el entusiasmo por un aprendizaje nutrido desde la curiosidad. La mayoría de los estudiantes coincidieron en lo valioso que les resultó el conocimiento adquirido, incluso han podido aprovechar estas experiencias para desarrollar un modelo funcional para sus respectivos PFG.Aroca Martínez, A.; Calles Díaz, H.; Chisbert Victory, D.; Cremades Navarro, MÁ.; Diago De Rozas, R.; Esplugues Calabuig, D.; Férez Navarro, M.... (2016). Proyecto docente innovador desarrollado en Grado en Ingeniería en Diseño Industrial y Desarrollo de Producto para la consecución de un Prototipo Funcional mediante trabajo en equipo. En In-Red 2016. II Congreso nacional de innovación educativa y docencia en red. Editorial Universitat Politècnica de València. https://doi.org/10.4995/INRED2016.2016.440

Impact of measurable residual disease by decentralized flow cytometry: a PETHEMA real-world study in 1076 patients with acute myeloid leukemia

The role of decentralized assessment of measurable residual disease (MRD) for risk stratification in acute myeloid leukemia (AML) remains largely unknown, and so it does which methodological aspects are critical to empower the evaluation of MRD with prognostic significance, particularly if using multiparameter flow cytometry (MFC). We analyzed 1076 AML patients in first remission after induction chemotherapy, in whom MRD was evaluated by MFC in local laboratories of 60 Hospitals participating in the PETHEMA registry. We also conducted a survey on technical aspects of MRD testing to determine the impact of methodological heterogeneity in the prognostic value of MFC. Our results confirmed the recommended cutoff of 0.1% to discriminate patients with significantly different cumulative-incidence of relapse (-CIR- HR:0.71, P < 0.001) and overall survival (HR: 0.73, P = 0.001), but uncovered the limited prognostic value of MFC based MRD in multivariate and recursive partitioning models including other clinical, genetic and treatment related factors. Virtually all aspects related with methodological, interpretation, and reporting of MFC based MRD testing impacted in its ability to discriminate patients with different CIR. Thus, this study demonstrated that “real-world” assessment of MRD using MFC is prognostic in patients at first remission, and urges greater standardization for improved risk-stratification toward clinical decisions in AML.This study was supported by the Centro de Investigación Biomédica en Red – Área de Oncología - del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369, CB16/12/00233, CB16/12/00284 and CB16/12/00400), Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS No. PI16/01661, PI16/00517 and PI18/01946), Gerencia Regional de Salud de CyL (GRS 1346/A/16) and the Plan de Investigación de la Universidad de Navarra (PIUNA 2014-18). This study was supported internationally by the Cancer Research UK, FCAECC and AIRC under the Accelerator Award Program EDITOR

Impact of FLT3–ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study

FLT3–ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of FLT3–ITD and its ratio in a series of 2901 adult patients treated intensively in the pre-FLT3 inhibitor era and reported in the PETHEMA registry. A total of 579 of these patients (20%) harbored FLT3–ITD mutations. In multivariate analyses, patients with an FLT3–ITD allele ratio (AR) of >0.5 showed a lower complete remission (CR rate) and OS (HR 1.47, p = 0.009), while AR > 0.8 was associated with poorer RFS (HR 2.1; p 0.5). Using the maximally selected log-rank statistics, we established an optimal cutoff of FLT3–ITD AR of 0.44 for OS, and 0.8 for RFS. We analyzed the OS and RFS according to FLT3–ITD status in all patients, and we found that the group of FLT3–ITD-positive patients with AR 0.44, allo-HSCT was superior to auto-HSCT in terms of OS and RFS. This study provides more evidence for a better characterization of patients with AML harboring FLT3–ITD mutations.This study was fundedby Instituto de Salud Carlos III (ISCIII) through the project PI19/01518 and PI19/00730 and co- funded by the European Union, the CRIS Against Cancer Foundation, grant 2018/001, and by the Instituto de Investigación Hospital 12 de Octubre (IMAS12). APeer reviewe

Long-Term Outcomes After Autologous Versus Allogeneic Stem Cell Transplantation in Molecularly-Stratified Patients With Intermediate Cytogenetic Risk Acute Myeloid Leukemia: A PETHEMA Study

PETHEMA (Programa Español de Tratamientos en Hematología) and GETH (Grupo Espa~nol de Trasplante Hematopoyético y Terapia Celular) Cooperative GroupsAcute myeloid leukemia (AML) with intermediate risk cytogenetics (IRcyto) comprises a variety of biological entities with distinct mutational landscapes that translate into differential risks of relapse and prognosis. Optimal postremission therapy choice in this heterogeneous patient population is currently unsettled. In the current study, we compared outcomes in IRcyto AML recipients of autologous (autoSCT) (n = 312) or allogeneic stem cell transplantation (alloSCT) (n = 279) in first complete remission (CR1). Molecular risk was defined based on CEBPA, NPM1, and FLT3-ITD mutational status, per European LeukemiaNet 2017 criteria. Five-year overall survival (OS) in patients with favorable molecular risk (FRmol) was 62% (95% confidence interval [CI], 50-72) after autoSCT and 66% (95% CI, 41-83) after matched sibling donor (MSD) alloSCT (P = .68). For patients of intermediate molecular risk (IRmol), MSD alloSCT was associated with lower cumulative incidence of relapse (P < .001), as well as with increased nonrelapse mortality (P = .01), as compared to autoSCT. The 5-year OS was 47% (95% CI, 34-58) after autoSCT and 70% (95% CI, 59-79) after MSD alloSCT (P = .02) in this patient subgroup. In a propensity-score matched IRmol subcohort (n = 106), MSD alloSCT was associated with superior leukemia-free survival (hazard ratio [HR] 0.33, P = .004) and increased OS in patients alive 1 year after transplantation (HR 0.20, P = .004). These results indicate that, within IRcyto AML in CR1, autoSCT may be a valid option for FRmol patients, whereas MSD alloSCT should be the preferred postremission strategy in IRmol patients.Supported by a Río Hortega academic clinical fellowship (CM19/00194) from the Instituto de Salud Carlos III, Spain (E.R.A.). Additional funding has been provided by CIBERONC grants to J.P.S. (CB16/12/00480), M.M.S. (CB16/12/00369) and B.V. (CB16/12/00233)