Tradicionalmente se ha concedido un papel subordinado a la mujer en las capitulaciones matrimoniales, documento básico en la regulación del régimen económico de la familia. Sin embargo, no eran raras ...las ocasiones en que la mujer alcanzaba protagonismo. El examen de varios centenares de capitulaciones del Alto Aragón nos ha permitido sacar a la luz esa realidad. Son muchos los casos en que sus progenitores u otros familiares la eligen como heredera, no siendo óbice la existencia de hermanos varones. Protagonismo también en las capitulaciones pactadas mediante la figura del agermanamiento, en el que la mujer aportaba la herencia y el varón la dote. Finalmente, protagonismo gracias a la viudedad foral, a la que se podía renunciar y que en ocasiones era sustituida por el “año de manto”, figura semejante al any de plor catalán y valenciano.
Les Pyrénées témoignent de la vigueur des échanges : les populations y commercent en toutes circonstances. Les sources font état d’échanges sur chacun des versants et entre le nord et le sud de la ...chaîne, et mettent en évidence un négoce transpyrénéen intéressant des marchés plus larges où la montagne et ses hommes ne participent qu’au transit des produits. Si une première approche permet d’entrevoir globalement le trafic, un certain nombre de questions se pose sur sa nature précise, l’influence des marches de part et d’autre des Pyrénées ou le rôle des marchands. Réunissant des chercheurs venus des deux côtés des Pyrénées, ces journées se fixent comme objectif de tester toutes les approches du sujet sous l’angle de l’histoire économique, sociale, culturelle, anthropologique et juridique.
Provider: - Institution: Gredos. Repositorio Documental de la Universidad de Salamanca - Data provided by Europeana Collections- Family conflict was a common experience in past families close as it ...is today. This study is based on the reason that led to family breaking in the XVIII Century Aragon and the lines society prescribed to avoid a total dissolution of a family kin. The most common causes annalyzed for these breakdowns were marriage plans, inheritances and domestic violence, all gathered in different lawsuits. Aragonese law affects to these situations in a different way that Castilian law did. The particular interpretations of Aragonese lawyers printed in the lawsuits their perception of human condition.- Rara es la familia que en un grado u otro, en un momento determinado no experimenta o ha vivido cierta tensión y conflicto entre sus componentes, ayer como hoy. Los motivos por los que aquellos surgieron en el Aragón del siglo XVIII, su incidencia y las distintas soluciones empleadas para ponerles fin centran un estudio en sintonía con las últimas corrientes historiográficas. Junto a una casuística bastante común basada principalmente, aunque no sólo, en enlaces conflictivos, malos tratos familiares y disputas por herencias y bienes, la peculiar legislación aragonesa aporta una serie de matices propios que contribuyen a perfilar con mayor nitidez algunos de estos problemas inherentes a la condición humana en todo lugar y momento.- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Herederos de una larga tradición de intercambios comerciales entre las dos vertientes pirenaicas, los pequeños comerciantes procedentes de Francia continuaban teniendo una fuerte presencia en el ...Norte de Aragón a fines del siglo XVIII. Procedentes de los valles limítrofes, a donde retornaban regularmente, algunos se especializaron en la venta ambulante. Tras elegir como centro de operaciones alguna de las localidades más populosas de la comarca – Barbastro, Monzón, Fraga o Tamarite de Litera–, en la que en ocasiones abrían un pequeño establecimiento, recorrían sus pueblos, ofertando casa a casa sus mercancías. En muchos casos, combinaban una actividad artesanal –fabricación de cedazos o calderos– con la venta de su producto y de otros géneros que podían ir desde los textiles al ganado porcino e incluso pequeñas cantidades de cereales. Sus clientes, modestos campesinos, compraban por lo general al fiado y el cobro de las deudas se vía facilitado por la existencia de unas relaciones de confianza recíproca. En apariencia modesta, este tipo de actividad comercial tenía una gran importancia en un mundo eminentemente rural al que le facilitaba el acceso al mercado.
Provider: - Institution: Gredos. Repositorio Documental de la Universidad de Salamanca - Data provided by Europeana Collections- La monarquía de los Austrias, como es de sobra conocido, topó con ...enormes dificultades en el gobierno de los estados de la Corona de Aragón. Los fueros y libertades de los distintos territorios impedían un ejercicio efectivo de la autoridad real y ello fue particularmente acusado en los casos del principado catalán y del reino aragonés. Por lo que a Aragón se refiere, el esquema de la modernidad podría resumirse del modo siguiente: frente a un siglo XVI en que el reino puso todo tipo de trabas al ejercicio de la autoridad real, en la centuria del seiscientos la monarquía había vencido cualquier resistencia y podía gobernar con la aquiescencia de la clase dirigente aragonesa.- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Abstract 4599
To prospectively analyze change over time in minimal residual disease (MRD) in a cohort of 84 untreated patients diagnosed with CD20+ B-CLL who received from October 2007 to December ...2010 six cycles of R-FC (Rituximab 375 mg/m2 IV in cycle 1 and 500 mg/m2 in cycles 2–6; F: 25 mg/m2, and C: 250 mg/m2 on days 1–3; every 28 days). Patients who achieved response were treated with rituximab 375 mg/m2 every 2 months for 3 years.
EDTA-anticoagulated peripheral blood (PB) and bone marrow (BM) samples were taken at diagnosis, after 3 and 6 cycles of R-FC, and every 6 months during the maintenance phase. MRD was centrally assessed by four-color multiparameter flow cytometry using the following antibody combinations: CD22/CD23/CD19/CD5, CD81/CD22/CD19/CD5, CD20/CD38/CD19/CD5, and CD20/CD79b/CD19/CD5. An acquisition was performed by selection of CD19+ cells/SSC including at least 200,000 events, reaching a sensitivity level of 0.01% (10-4).
PB/BM samples for assessing MRD were available from 28 of the 84 patients after 3 cycles of R-FC and from 79 patients after the 6 induction cycles, and 43 (58%) of the 74 patients on maintenance reached the interim study at 18 months of maintenance (9 cycles). Correlation between PB and BM was 57%, 68%, and 86% at the three study time points. After three R-FC cycles, 16 patients (56.8%) had a MRD- in PB, but only 4 patients (14%) also had MRD- in BM. After six R-FC cycles, 58 patients (73.3%) had a negative study in PB, and 41.7% also in BM. Among the 24 patients analyzed after the third cycle with BM+, 11 achieved negativization after 6 cycles, and MRD was negative in PB in 10 of 12 patients. After 18 months of maintenance, 11 patients (26.2%) converted to MRD- in PB/BM, and a single patient (2.4%) converted to MRD+.
Six cycles of R-FC achieved better MRD- rates in PB and BM as compared to 3 cycles. Addition of rituximab as maintenance after R-FC increased the number of MRD-negative in BM, and in consequence the MRD-negative CRs. A good correlation was not found between MRD values in blood and bone marrow in the induction phase. However, these levels improved in the maintenance phase due to an increase in the number of cases with RMD-negative in BM witch were negatives in PB during induction phase.
Off Label Use: R in Maintenance.
Abstract 2448
Combination of Rituximab (R) with fludarabine (F) and cyclophosphamide (C) as first line treatment of B-CLL, results in a high complete response rate, improved progression free and ...overall survival compared with FC in randomised trials (Hallek et al, Blood 2009). However, more than 30% of patients relapse or show disease progression at 3–4 years after FR or FCR treatment (Byrd et al., Blood 2005; Keating et al., J Clin Oncol 2005). We report on the efficacy and safety results of an interim analysis after one year of Rituximab maintenance (Rm) following FCR in previously untreated CLL patients (pts). Methods and Patients. Between October 2007 and June 2009, a cohort of 84 physically fit pts with CD20 positive CLL received treatment with 6 cycles of FCR (R:375mg/m2 iv cycle-1 and 500mg/m2 iv, cycles 2–6; F:25mg/m2 iv, days 1–3; and C:250mg/m2 iv days 1–3; every 28 days). After 3 months of clinical response evaluation, pts achieving a response were treated with R: 375mg/m2 iv every 2 months for 3 years. Anti-infective prophylaxis included trimethoprim-sulfamethoxazole and acyclovir during treatment and until CD4 positive lymphocyte reached 0.3×109/L. Pts achieving a complete response (CR) and negative minimal residual disease (MRD) in peripheral blood (PB) and bone marrow (BM) after 4 courses of FCR, were allowed to stop FC and complete 2 courses of R and continue with Rm. The median age was 59.5 (range 37–70), 32% were females, 6% were Rai low risk, 69% intermediate risk and 25% high risk stage. IGHV status was unmutated in 64.4%, CD38 positive (>30%) in 47.6% and ZAP-70 positive (>20%) in 57.3% of pts. The incidence of genetic abnormalities by FISH for del 6q, del 11q (ATM), trisomy 12, del 13q and del 17p (p53) was 3.5%, 26.1%,15,4%, 50% and 4.7% respectively. MRD was evaluated by multicolor flow cytometry (sensitivity: 1 CLL cell positive in 10000 leukocytes). The primary end point was to evaluate the response rates and adverse events (AEs) profile of FCR and Rm treatments. Secondary endpoints included progression free and overall survival, correlation of response with MRD after FCR and Rm treatments. The mean number of FCR cycles was 5.3, and the complete treatment was administered in 80% of pts.
We present the results of a planned interim analysis after 1 year (6 cycles) of Rm following FCR as induction treatment. Of 90 pts screened from 29 centres, 84 were assigned (6 failed eligible criteria) to FCR and were evaluable for response. On an intent to treat analysis, overall response, CR, partial response (PR), non response and progression rates were 95.2%, 73.8%, 21.4%, 3.6% and 1.2% respectively. Of 79 pts evaluable for BM-MRD status, MRD-negative CR, MRD-positive CR, MRD-negative PR and MRD-positive PR rates were 57%, 21.5%, 7.6% and 13.9% respectively. The most common AEs after FCR were rituximab infusion (65.1%), myelotoxicity (33.7%) in 29 pts and infections (34%) with 1 serious AEs (SAEs)(1 exitus by viral myocarditis). In addition, there were 12 non hematological SAEs. Seventy five out of 84 pts continued with Rm treatment, 9 were withdrawn by progression (1), toxicity (5) and investigator decision (3). As of June 2010, 70 out 75 eligible pts had initiated Rm and 37 (49.3%) had completed 1 year of Rm (6 cycles) and were evaluable for response. Of them, 24 (64.8%) pts were in MRD-negative CR and only 1 pts converted to MRD-positive CR; 8 (21, 6%) pts were in MRD-positive CR and 3 converted to MRD-Negative CR, while 5 (13.5%) continued in MRD-positive CR with a sustained decreasing number of CLL cells in BM. Five pts were in MRD-positive PR and of them, 4 were in sustained PR with BM-MRD response and one pts presented clinical progression. In summary, 70.2% reached MRD-negative CR and 97.3% were in sustained response. The most common AEs after Rm were grade 3/4 neutropenia between cycles in 6 (16.7%) pts, infections in 15 (41.7%) pts and there were 2 (5.6%) SAEs (2 pneumonia) reported in this population.
Based on these preliminary results, the addition of rituximab maintenance following FCR is feasible and effective in untreated CLL pts and increases the quality of clinical responses by obtaining a higher number of MRD-negative CR cases with an acceptable safety profile.
Garcia-Marco: ROCHE: Consultancy, Honoraria, Research Funding. Off Label Use: Rituximab is not approved as maintenance therapy. Leon: ROCHE: Employment.
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