Therapeutic targets and microenvironment in sequential biopsies of classical Hodgkin lymphoma at diagnosis and relapse

Classical Hodgkin lymphoma is dominated by the non-neoplastic microenvironment, while the neoplastic Hodgkin-Reed-Sternberg cells compose only a minority of cells in the lymphoma tissue. Both the Hodgkin-Reed-Sternberg cells due to their expression of CD30 and PD-L1 and the microenvironment with abundant T cells and expression of PD1 are specifically targeted by new treatment concepts. We aimed to understand the dynamics of therapeutic targets in patients treated with conventional chemotherapy. We analyzed sequential biopsy specimens obtained at diagnosis and at relapse from the same patient for morphology, immunophenotype, and microenvironmental components. The morphological subtype changed between primary and relapse biopsy in 20% of cases. The immunophenotype was stable with respect to CD30, CD3, and LMP1 but variable with respect to CD15 and CD20 expression. Gene expression revealed 8 upregulated and 20 downregulated genes at relapse (p <= 0.05) with a consistent logarithmic fold change direction in at least 75% of all cases. For PD1, we found discrepant results between gene expression analysis (decrease at relapse) and number of PD1-positive cells assessed by immunohistochemistry (unchanged at relapse). PD-L1 in the neoplastic cells appeared unchanged between primary diagnosis and relapse. The expression of the therapeutic targets CD30, PD1, and PD-L1 can reliably be assessed in tumor specimen at first diagnosis and is unchanged under conventional chemotherapy

Proceedings of the 2nd Workshop on Flavor Symmetries and Consequences in Accelerators and Cosmology (FLASY12)

These are the proceedings of the 2nd Workshop on Flavor Symmetries and Consequences in Accelerators and Cosmology, held 30 June 2012 - 4 July 2012, Dortmund, Germany.Comment: Order 400 pages, several figures including the group picture v2: corrected author list and contributio

Hydraulic engineering in the 21st century: Where to?

For centuries, hydraulic engineers were at the forefront of science. The last forty years marked a change of perception in our society with a focus on environmental sustainability and management, particularly in developed countries. Herein, the writer illustrates his strong belief that the future of hydraulic engineering lies upon a combination of innovative engineering, research excellence and higher education of quality. This drive continues a long tradition established by eminent scholars like Arthur Thomas IPPEN, John Fisher KENNEDY and Hunter ROUSE

Masonry dams : analysis of the historical profiles of Sazilly, Delocre and Rankine

The significant advances in masonry dam design that took place in the second half of the 19th century are analyzed and discussed within the context of the historical development of dam construction. Particular reference is made to the gravity dam profiles proposed by Sazilly, Delocre and Rankine, who pioneered the application of engineering concepts to dam design, basing the dam profile on the allowable stresses for the conditions of empty and full reservoir. These historical profiles are analyzed taking into consideration the present safety assessment procedures, by means of a numerical application developed for this purpose, based on limit analysis equilibrium methods, which considers the sliding failure mechanisms, the most critical for these structures. The study underlines the key role of uplift pressures, which was only addressed by Lévy after the accident of Bouzey dam, and provides a critical understanding of the original design concepts, which is essential for the rehabilitation of these historical structures.This work has been funded by FCT (Portuguese Foundation for Science and Technology) through the PhD grant SFRH/BD/43585/2008, for which the first author is grateful

Validación del Cuestionario de Creencias Centrales de los Trastornos de la Personalidad (CCE-TP) en población colombiana

Se construyó un cuestionario para evaluar creencias centrales asociadas con los trastornos de la personalidad, fundamentadas en el Modelo de la Terapia Cognitiva. Se realizó el análisis estructural y la validez de contenido de la prueba en población universitaria de la ciudad de Medellín, Colombia. La muestra fue representativa y elegida al azar a través de un procedimiento polietápico. Un número de 809 estudiantes universitarios contestaron el cuestionario de creencias centrales de los trastornos de la personalidad (CCE-TP). Se realizó un análisis factorial exploratorio de la prueba, reagrupándose los ítems en 14 factores (F) que representan el 61,3% de la varianza. F1: CCE-TP antisocial (8 ítems, a 0,839); F2: CCE-TP esquizotípico/límite (8 ítems, a 0,846); F3: CCE-TP histriónico/patrón seductor (6 ítems, a 0,833); F4: CCE-TP paranoide (6 ítems, a 0,836); F5: CCE-TP por evitación / autopercepción negativa (5 ítems, a 0,755); F6: CCE-TP por dependencia (5 ítems, a 0,797); F7: CCE-TP histriónico/ dependencia emocional (4 ítems, a 0,755); F8: CCETP obsesivo-compulsivo/perfeccionista (4 ítems, a 0,808); F9: CCE-TP por evitación/hipersensible (4 ítems, a 0,766); F10: CCE-TP obsesivo-compulsivo/ crítico frente a los demás (3 ítems, a 0,851); F11: CCE-TP narcisista (4 ítems, a 0,717); F12: CCE-TP pasivo-agresivo / temor a ser dominado (3 ítems, a 0,719); F13: CCE-TP pasivo-agresivo/crítico frente a la autoridad (3 ítems, a 0,685), y F14: CCE-TP esquizoide (2 ítems, a 0,774). El alfa de Cronbach de la prueba fue de 0,931

Validación del Cuestionario de Creencias Centrales de los Trastornos de la Personalidad (CCE-TP) en población colombiana

Se construyó un cuestionario para evaluar creencias centrales asociadas con los trastornos de la personalidad, fundamentadas en el Modelo de la Terapia Cognitiva. Se realizó el análisis estructural y la validez de contenido de la prueba en población universitaria de la ciudad de Medellín, Colombia. La muestra fue representativa y elegida al azar a través de un procedimiento polietápico. Un número de 809 estudiantes universitarios contestaron el cuestionario de creencias centrales de los trastornos de la personalidad (CCE-TP). Se realizó un análisis factorial exploratorio de la prueba, reagrupándose los ítems en 14 factores (F) que representan el 61,3% de la varianza. F1: CCE-TP antisocial (8 ítems, a 0,839); F2: CCE-TP esquizotípico/límite (8 ítems, a 0,846); F3: CCE-TP histriónico/patrón seductor (6 ítems, a 0,833); F4: CCE-TP paranoide (6 ítems, a 0,836); F5: CCE-TP por evitación / autopercepción negativa (5 ítems, a 0,755); F6: CCE-TP por dependencia (5 ítems, a 0,797); F7: CCE-TP histriónico/ dependencia emocional (4 ítems, a 0,755); F8: CCETP obsesivo-compulsivo/perfeccionista (4 ítems, a 0,808); F9: CCE-TP por evitación/hipersensible (4 ítems, a 0,766); F10: CCE-TP obsesivo-compulsivo/ crítico frente a los demás (3 ítems, a 0,851); F11: CCE-TP narcisista (4 ítems, a 0,717); F12: CCE-TP pasivo-agresivo / temor a ser dominado (3 ítems, a 0,719); F13: CCE-TP pasivo-agresivo/crítico frente a la autoridad (3 ítems, a 0,685), y F14: CCE-TP esquizoide (2 ítems, a 0,774). El alfa de Cronbach de la prueba fue de 0,931