Clinical validation of the EndoPredict test in node-positive, chemotherapy-treated ER+/HER2− breast cancer patients: results from the GEICAM 9906 trial

INTRODUCTION: EndoPredict (EP) is an RNA-based multigene test that predicts the likelihood of distant recurrence in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2–negative (HER2−) breast cancer (BC) who are being treated with adjuvant endocrine therapy. Herein we report the prospective-retrospective clinical validation of EP in the node-positive, chemotherapy-treated, ER+/HER2− BC patients in the GEICAM 9906 trial. METHODS: The patients (N = 1,246) were treated either with six cycles of fluorouracil, epirubicin and cyclophosphamide (FEC) or with four cycles of FEC followed by eight weekly courses of paclitaxel (FEC-P), as well as with endocrine therapy if they had hormone receptor–positive disease. The patients were assigned to EP risk categories (low or high) according to prespecified cutoff levels. The primary endpoint in the clinical validation of EP was distant metastasis-free survival (MFS). Metastasis rates were estimated using the Kaplan-Meier method, and multivariate analysis was performed using Cox regression. RESULTS: The molecular EP score and the combined molecular and clinical EPclin score were successfully determined in 555 ER+/HER2− tumors from the 800 available samples in the GEICAM 9906 trial. On the basis of the EP, 25% of patients (n = 141) were classified as low risk. MFS was 93% in the low-risk group and 70% in the high-risk group (absolute risk reduction = 23%, hazard ratio (HR) = 4.8, 95% confidence interval (CI) = 2.5 to 9.5; P < 0.0001). Multivariate analysis showed that, in this ER+/HER2− cohort, EP results are an independent prognostic parameter after adjustment for age, grade, lymph node status, tumor size, treatment arm, ER and progesterone receptor (PR) status and proliferation index (Ki67). Using the predefined EPclin score, 13% of patients (n = 74) were assigned to the low-risk group, who had excellent outcomes and no distant recurrence events (absolute risk reduction vs high-risk group = 28%; P < 0.0001). Furthermore, EP was prognostic in premenopausal patients (HR = 6.7, 95% CI = 2.4 to 18.3; P = 0.0002) and postmenopausal patients (HR = 3.3, 95% CI = 1.3 to 8.5; P = 0.0109). There were no statistically significant differences in MFS between treatment arms (FEC vs FEC-P) in either the high- or low-risk groups. The interaction test results between the chemotherapy arm and the EP score were not significant. CONCLUSIONS: EP is an independent prognostic parameter in node-positive, ER+/HER2− BC patients treated with adjuvant chemotherapy followed by hormone therapy. EP did not predict a greater efficacy of FEC-P compared to FEC alone

Validity of Body Shape Questionnaire (BSQ) in Mexican women / Validez del Body Shape Questionnaire (BSQ) en mujeres mexicanas

Abstract. The aim of this study was to validate the instrument Body Shape Questionnaire (BSQ) in female Mexican population, created to assess body dissatisfaction. 472 women participated, 256 were students and formed the control group ('X = 15.9, DE = 3.2)  and 216 patients with Eating Disorders (ED) ('X = 20.5,  DE = 3.9)  with an age range of 13 to 30 years. The results showed excellent internal consistency (a = .98) and a 2-factor structure that explained 63.8% of the total variance. These were: 1) normative body uncomfort (α=.95), and 2) pathological body uncomfort (α=.94). Regarding the discriminant and predictive validity, the BSQ showed good ability to classify individuals with eating disorders, depending on body dissatisfaction, noting that such capacity is greater when discriminating between Anorexia, Bulimia and control (λ de Wilks = .485, χ2(gl=1)= 278.830, p≤ .001). Finally we explored 6 different cut off points, of which the 110-was proved to be the most appropriate according to their values ​​of sensitivity (84.3%) and specificity (84.4%). In conclusion, the BSQ is a useful questionnaire to detect body dissatisfaction in Mexican women. Keywords: Validity, Body Shape Questionnaire, women, body dissatisfaction. Resumen. El objetivo de la presente investigación fue validar el instrumento en población mexicana femenina Body Shape Questionnaire (BSQ), creado con la finalidad de evaluar la insatisfacción corporal. Participaron 472 mujeres, 256 eran estudiantes ('X = 15.9, DE = 3.2) y conformaron el grupo control y 216 pacientes con Trastorno del Comportamiento Alimentario (TCA) ('X = 20.5,  DE = 3.9) con un rango de edad de 13 a 30 años. Los resultados mostraron una excelente consistencia interna (a =  .98), así como una estructura de 2 factores que explicaron el 63.8% de la varianza total. Estos fueron: 1) Malestar corporal normativo (α=.95) y 2) Malestar  corporal patológico (α=.94). Respecto a la validez discriminante y predictiva, el BSQ mostró una buena capacidad de clasificar a individuos con TCA, en función de la insatisfacción corporal, y se observó que dicha capacidad es mayor cuando discrimina entre Anorexia, Bulimia y control (λ de Wilks = .485, χ2(gl=1)= 278.830, p≤ .001). Finalmente se exploraron 6 diferentes puntos de corte, de los cuales 110 fue el que demostró ser el más apropiado, de acuerdo a sus valores de sensibilidad (84.3%) y especificidad (84.4%). En conclusión el BSQ es un cuestionario de gran utilidad para detectar la insatisfacción corporal en  mujeres mexicanas. Palabras clave: Validez, Body Shape Questionnaire, mujeres, insatisfacción corporal

The Obestatin/GPR39 System Is Up-regulated by Muscle Injury and Functions as an Autocrine Regenerative System

Background: Satellite cell activation is orchestrated by several signals, which induce their differentiation into skeletal muscle fibers. Results: Obestatin and the GPR39 receptor exert an autocrine role on the control of myogenesis. Conclusion: Our data indicate that obestatin/GPR39 is an injury-regulated signal that functions as a myogenic regenerative system. Significance: Strategies to enhance obestatin-mediated signaling could be useful in treating trauma-induced muscle injuries and skeletal muscle myopathies

Nanostructured Steels

Chapter 8 Nanostructured SteelsNanostructured metals with grain sizes smaller than 100 nm usually exhibit strengths which can be more than twice higher than their coarse-grained counterparts. The “smaller is stronger” effect is generally understood in terms of the Hall-Petch effect of grain size strengthening, or the capability of grain boundaries to obstruct the motion of dislocations as carriers of plastic deformation. Nanostructured steels take benefit of reductions in the grain size to show improved tensile strength, hardness and in-service properties. The steel nanostructures are usually multi-phase and hierarchical, maintaining or even improving the stress-ductility trade-off. The increasing demands for stronger, tougher, wear resistant and heat-tolerant materials have led to the development of new families of steels where the length scale that controls such properties is in the nanometer range. This chapter provides an overview of the current status of the most technologically relevant bulk nanostructured steels, describing the approaches to metallurgical design, processing routes, mechanical properties, in-use behavior and industrial applications.The authors acknowledge financial support from the Spanish Ministerio de Economia y Competitividad (MINECO) in the form of a coordinate project (MAT2016-80875-C3-1-R) and the Research Fund for Coal and Steel of the European Commission under the contract SuperHigh (RFSR-CT-2014-00019)

A Constitutive Relationship between Fatigue Limit and Microstructure in Nanostructured Bainitic Steels

The recently developed nanobainitic steels show high strength as well as high ductility. Although this combination seems to be promising for fatigue design, fatigue properties of nanostructured bainitic steels are often surprisingly low. To improve the fatigue behavior, an understanding of the correlation between the nanobainitic microstructure and the fatigue limit is fundamental. Therefore, our hypothesis to predict the fatigue limit was that the main function of the microstructure is not necessarily totally avoiding the initiation of a fatigue crack, but the microstructure has to increase the ability to decelerate or to stop a growing fatigue crack. Thus, the key to understanding the fatigue behavior of nanostructured bainite is to understand the role of the microstructural features that could act as barriers for growing fatigue cracks. To prove this hypothesis, we carried out fatigue tests, crack growth experiments, and correlated these results to the size of microstructural features gained from microstructural analysis by light optical microscope and EBSD-measurements. Finally, we were able to identify microstructural features that influence the fatigue crack growth and the fatigue limit of nanostructured bainitic steels

Ductility of Nanostructured Bainite

Nanostructured bainite is a novel ultra-high-strength steel-concept under intensive current research, in which the optimization of its mechanical properties can only come from a clear understanding of the parameters that control its ductility. This work reviews first the nature of this composite-like material as a product of heat treatment conditions. Subsequently, the premises of ductility behavior are presented, taking as a reference related microstructures: conventional bainitic steels, and TRIP-aided steels. The ductility of nanostructured bainite is then discussed in terms of work-hardening and fracture mechanisms, leading to an analysis of the three-fold correlation between ductility, mechanically-induced martensitic transformation, and mechanical partitioning between the phases. Results suggest that a highly stable/hard retained austenite, with mechanical properties close to the matrix of bainitic ferrite, is advantageous in order to enhance ductility

Chino Básico 2 - TR196 - 202102

El curso de Chino básico 2 está basado en el enfoque comunicativo que permite al estudiante comprender información y expresarse de manera oral y escrita acerca de temas cotidianos y de su entorno personal, así como familiarizarse con los aspectos históricos y culturales de China, utilizando el vocabulario y las estructuras gramaticales básicas del idioma. Este curso permitirá al estudiante interiorizar el sistema fonético del chino para poder empezar y familiarizarse con la escritura de caracteres. De esta manera, se obtendrá el conocimiento básico de la lengua y la cultura china. Al mismo tiempo, desarrollará su capacidad auditiva y lectora que le permitirá rendir el examen de suficiencia de chino (HSK 1) de forma satisfactoria. Además, contribuye al desarrollo de la competencia general comunicación escrita y competencias específicas Segundas lenguas ambas a nivel 1