TP53, ATRX alterations, and low tumor mutation load feature IDH-wildtype giant cell glioblastoma despite exceptional ultra-mutated tumors

Background: Giant cell glioblastoma (gcGBM) is a rare morphological variant of IDH-wildtype (IDHwt) GBM that occurs in young adults and have a slightly better prognosis than "classic" IDHwt GBM. Methods: We studied 36 GBMs, 14 with a histopathological diagnosis of gcGBM and 22 with a giant cell component. We analyzed the genetic profile of the most frequently mutated genes in gliomas and assessed the tumor mutation load (TML) by gene-targeted next-generation sequencing. We validated our findings using The Cancer Genome Atlas (TCGA) data. Results: p53 was altered by gene mutation or protein overexpression in all cases, while driver IDH1, IDH2, BRAF, or H3F3A mutations were infrequent or absent. Compared to IDHwt GBMs, gcGBMs had a significant higher frequency of TP53, ATRX, RB1, and NF1 mutations, while lower frequency of EGFR amplification, CDKN2A deletion, and TERT promoter mutation. Almost all tumors had low TML values. The high TML observed in only 2 tumors was consistent with POLE and MSH2 mutations. In the histopathological review of TCGA IDHwt, TP53-mutant tumors identified giant cells in 37% of the cases. Considering our series and that of the TCGA, patients with TP53-mutant gcGBMs had better overall survival than those with TP53wt GBMs (log-rank test, P < .002). Conclusions: gcGBMs have molecular features that contrast to "classic" IDHwt GBMs: unusually frequent ATRX mutations and few EGFR amplifications and CDKN2A deletions, especially in tumors with a high number of giant cells. TML is frequently low, although exceptional high TML suggests a potential for immune checkpoint therapy in some cases, which may be relevant for personalized medicine

An?lisis de medidas que implementadas por productores ganaderos durante un periodo de verano prolongado en Guanacaste, Costa Rica

Ponencia presentada en: VII Congresso Latinoamericano de Sistemas Agroflorestais para a Producao Pecu?ria Sustent?velEn las ?ltimas d?cadas, los efectos del cambio clim?tico han ocasionado ?pocas secas cada vez m?s extensas y/o periodos de lluvias m?s cortos para la regi?n del Pacifico Norte de Costa Rica. Estudios indican que la mayor?a de eventos extremos secos en esa regi?n se encuentran asociados al fen?meno meteorol?gico de El Ni?o (ENOS). Para el presente estudio, se tom? como referencia el periodo comprendido entre junio del 2009 y abril del 2010 por presentarse un verano seco muy prolongado (8 meses) debido a ENOS, lo que origin? un d?ficit de agua de hasta un 35% seg?n reportes del Instituto Meteorol?gico Nacional de Costa Rica(IMN). Para esto, los sistemas de producci?n se vieron en la necesidad de emplear diferentes medidas de adaptaci?n. Tres sistemas de fincas fueron identificados: 1) fincas de producci?n intensiva; uso de bancos forrajeros, pasturas mejoradas y bebederos, 2) fincas de producci?n semi intensiva; con uso de bancos forrajeros y bebederos 3) fincas con producci?n extensiva; con bajo o nulo uso de bancos forrajeros, pasturas mejoradas y bebederos. Las variables que m?s explicaron la funci?n de descarga o salida de animales por parte de los productores como ajuste en la carga animal en orden de significancia fueron la implementaci?n de bancos forrajeros (P=0.0007), pasturas mejoradas de alta densidad arb?rea (P=0.0016) y la disponibilidad que tienen los animales hacia sus bebederos (P=0.0032)

C?lculo de la huella h?drica para producir un litro de leche en fincas ganaderas en Jinotega y Matigu?s, Nicaragua

Ponencia presentada en: VII Congresso Latinoamericano de Sistemas Agroflorestais para a Producao Pecu?ria Sustent?velAl sector pecuario se le atribuye ser el responsable del 8 % del consumo mundial de agua y probablemente su mayor fuente de contaminaci?n. La Huella h?drica es considerada como un indicador de uso de agua. El presente estudio tiene por objetivo estimar la huella h?drica, cantidad de agua usada para producir un litro de leche, en fincas ganaderas de los municipios de Matigu?s y Jinotega en Nicaragua. Previo inventario y georefenciaci?n de 30 fincas lecheras en ambos municipios, 10 fincas al azar fueron seleccionadas en cada una de las zonas de estudio. En dichas fincas se determin? i) su tipolog?a, con base a caracter?sticas de la finca; ii) consumo de agua, directo e indirecto; y iii) uso de agua con base a la descripci?n y cuantificaci?n del uso de agua de las diferentes actividades que usan agua en la fase de producci?n de leche. An?lisis estad?sticos b?sicos, de conglomerados y multivariados fueron usados en el an?lisis de los datos. Entre los resultados se tiene que el consumo directo de agua por parte de vacas en producci?n es aproximadamente el 7,5 % de su peso vivo y que la huella h?drica para la producci?n de un litro de leche fue de 950 en las fincas ganaderas de Matig?as y 1500 litros de agua en Jinotega. Aunque los resultados son coherentes con c?lculos realizados y/o proyectados por otros estudios, es importante recalcar que se necesita mayor tiempo de evaluaci?n y un mayor tama?o de la muestra para tener datos m?s ajustados

Home range estimation within complex restricted environments: importance of method selection in detecting seasonal change

Estimating the home ranges of animals from telemetry data can provide vital information on their spatial behaviour, which can be applied by managers to a wide range of situations including reserve design, habitat management and interactions between native and non-native species. Methods used to estimate home ranges of animals in spatially restricted environments (e.g. rivers) are liable to overestimate areas and underestimate travel distances by including unusable habitat (e.g. river bank). Currently, few studies that collect telemetry data from species in restricted environments maximise the information that can be gathered by using the most appropriate home-range estimation techniques. Simulated location datasets as well as radio-fix data from 23 northern pike (Esox lucius) were used to examine the efficiency of home-range and travel estimators, with and without correction for unusable habitat, for detecting seasonal changes in movements. Cluster analysis most clearly demonstrated changes in range area between seasons for empirical data, also showing changes in patchiness, and was least affected by unusable-environment error. Kernel analysis showed seasonal variation in range area more clearly than peripheral polygons or ellipses. Range span, a linear estimator of home range, had no significant seasonal variation. Results from all range area estimators were smallest in autumn, when cores were least fragmented and interlocation movements smallest. Cluster analysis showed that core ranges were largest and most fragmented in summer, when interlocation distances were most variable, whereas excursion-sensitive methods (e.g. kernels) recorded the largest outlines in spring, when interlocation distances were largest. Our results provide a rationale for a priori selection of home-range estimators in restricted environments. Contours containing 95% of the location density defined by kernel analyses better reflected excursive activity than ellipses or peripheral polygons, whereas cluster analyses better defined range cores in usable habitat and indicate range fragmentation

A comparison of physicians' end-of-life decision making for non-western migrants and Dutch natives in the Netherlands

Background: Non-western migrants have a different cultural background that influences their attitudes towards healthcare. As the first wave of this relatively young group is growing older, we investigated, for the first time, whether end-of-life decision-making practices for non-western migrants differ from Dutch natives. Methods: In 2005, we sent questionnaires to physicians who attended deaths identified from the central death registry of Statistics Netherlands (n = 9651; non-western migrants: n = 627, total response: 78%). We performed multivariate logistic regression analyses adjusted for age, sex and cause of death. Results: Of all deaths of non-western origin, 54% were non-sudden, whereas 67% of all deaths with a Dutch origin were non-sudden (P = 0.00). A relatively large number of non-suddenly deceased persons of non-western origin had died under the age of 65 (53%) as compared to Dutch natives (15%). Euthanasia was performed in 2.4% of all non-suddenly deceased persons in the non-western migrant group as compared to 2.7% in the native Dutch group (adjusted odds ratio = 0.82, P = 0.63). Alleviation of symptoms with a potential life-shortening effect was somewhat lower for non-western migrants (30% vs. 38%; adjusted odds ratio = 0.78, P = 0.07). Physicians decided to forgo potentially life-prolonging treatment in comparable rates (26% vs. 23%; adjusted odds ratio = 1.1, P = 0.73). Yet, the type of treatments forgone and underlying reasons differed. Conclusion: Euthanasia was not less common among non-suddenly deceased non-western migrants as compared to Dutch natives. However, intensive symptom alleviation was used less frequently and forgoing potentially life-prolonging treatment involved different characteristics. These findings suggest that cultural factors may affect end-of-life decision making