Plasma Level of Mmp-9 as Predictive Factor for Response and Progression Free Survival in Patients Treated with Bevacizumab (Bev) and Pegylated Liposomal Doxorubicin (Pld): Sakk 24/06

Background: There is currently no identified marker predicting benefit from Bev in patients with breast cancer (pts). We monitored prospectively 6 angiogenesis-related factors in the blood of advanced stage pts treated with a combination of Bev and PLD in a phase II trial of the Swiss Group for Clinical Cancer Research, SAKK.Methods: Pts received PLD (20 mg/m2) and Bev (10 mg/kg) every 2 weeks for a maximum of 12 administrations, followed by Bev monotherapy until progression or severe toxicity. Blood samples were collected at baseline, during treatment and at treatment discontinuation. Enzyme-linked immunosorbent assays (Quantikine, R&DSystems and Reliatech) were used to measure vascular endothelial growth factor (VEGF), placental growth factor (PlGF), matrix metalloproteinase 9 (MMP-9) and soluble VEGF receptors -1, -2 and -3. The natural log-transformed (ln) data for each factor was analyzed by analysis of variance (ANOVA) model to investigate differences between the mean values of the subgroups of interest (where a = 0.05), based on the best tumor response by RECIST.Results: 132 samples were collected in 41 pts. The mean of baseline ln MMP-9 levels was significantly lower in pts with tumor progression than those with tumor response (p=0.0202, log fold change=0.8786) or disease control (p=0.0035, log fold change=0.8427). Higher MMP-9 level was a significant predictor of superior progression free survival (PFS): p=0.0417, hazard ratio=0.574, 95% CI=0.336-0.979. In a multivariate cox proportional hazards model, containing performance status, disease free interval, number of tumor sites, visceral involvement and prior adjuvant chemotherapy, using stepwise regression baseline MMP-9 was still a statistically 117P Table 1. SOLTI-0701* AC01B07* NU07B1* SOR+CAP N=20 PL+CAP N=33 SOR+ GEM/CAP N=23 PL+ GEM/CAP N=27 SOR+PAC N=48 PL+PAC N=46 Baseline characteristics Age, median (range), y 49 (32-72) 53 (30-78 54 (32-69) 57 (31-82) 50 (27-80) 52 (23-74) AJCC stage, n (%) IIIB/IIIC 3 (15) 6 (18) 0 (0) 3 (11) 8 (17) 9 (20) IV 17 (85) 27 (82) 23 (100) 24 (89) 40 (83) 37 (80) Metastatic site, n (%) Non-visceral 3 (15) 6 (18) 7 (30) 6 (22) 9 (19) 17 (37) Visceral 17 (85) 27 (82) 16 (70) 21 (78) 39 (81) 29 (63) Prior metastatic chemo, n (%) 8 (40) 15 (45) 21 (91) 25 (93) - - Efficacy PFS, median, mo 4.3 2.5 3.1 2.6 5.6 5.5 HR (95% CI)_ 0.60 (0.31, 1.14) 0.57 (0.30, 1.09) 0.86 (0.50, 1.45) 1-sided P value_ 0.055 0.044 0.281 Overall survival, median, mo 17.5 16.1 Pending 14.7 18.2 HR (95% CI)_ 0.98 (0.50, 1.89) 1.11 (0.64, 1.94) 1-sided P value_ 0.476 0.352 Safety N=20 N=33 N=22 N=27 N=46 N=46 Tx-emergent Grade 3/4, n (%) 15 (75) 16 (48) 20 (91) 17 (63) 36 (78) 16 (35) Grade 3§ hand-foot skin reaction/ syndrome 8 (40) 5 (15) 8 (36) 0 (0) 14 (30) 2 (4) *Efficacy results based on intent-to-treat population and safety results based on safety population (pts who received study drug[s]); _Cox regression within each subgroup; _log-rank test within each subgroup; §maximum toxicity grade for hand-foot skin reaction/syndrome; AJCC, American Joint Committee on Cancer mittedabstractsª The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com Downloaded from annonc.oxfordjournals.org at Bibliotheque Cantonale et Universitaire on June 6, 2011 significant factor (p=0.0266). The results of the other measured factors were presented elsewhere.Conclusions: Higher levels of MMP-9 could predict tumor response and superior PFSin pts treated with a combination of Bev and PLD. These exploratory results justify further investigations of MMP-9 in pts treated with Bev combinations in order to assess its role as a prognostic and predictive factor.Disclosure: K. Zaman: Participation in advisory board of Roche; partial sponsoring ofthe study by Roche (the main sponsor was the Swiss Federation against Cancer (Oncosuisse)). B. Thu¨rlimann: stock of Roche; Research grants from Roche. R. vonMoos: Participant of Advisory Board and Speaker honoraria

Gamma Knife radiosurgery after previous microvascular decompression decreases the chances of pain free in classical trigeminal neuralgia

Purpose: To evaluate the safety-efficacy of Gamma Knife surgery (GKS) as a second treatment for classical trigeminal neuralgia (CTN), and the influence of prior microvascular decompression (MVD). Methods: Between July 1992 and November 2010, 737 patients have been operated with GKRS for ITN and prospectively evaluated in Timone University Hospital in Marseille, France. Among these, 54 patients had a previous history of MVD. Radiosurgery using a Gamma Knife (model B or C or Perfexion) was performed on the basis of on both MR and CT targeting. A single 4 mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 3.9-11.9) anteriorly to the emergence of the nerve (retrogasserian target). A median maximum dose of 85 Gy (range 70-90) was delivered. Here, the 45 patients with previous MVD and a follow-up longer than one year are evaluated (the patients with megadolichobasilar artery compression and multiple sclerosis were excluded). Results: The median age in this series was 56.75 years (range 28.09-82.39). The median follow-up period was 39.48 months (range 14.10-144.65). All the patients had a past history of surgery, with at least one previous failed MVD, but also radiofrequency lesion (RFL) in 16 patients (35.6%), balloon microcompression in 7 (15.6%) and glycerol rhizotomy in 1 (2.2%). Thirty-five patients (77.8%) were initially pain free after GKS within a median time of 14 days (range 0, 180). Patients from this group had less probability of being pain free compared to our global population of essential trigeminal neuralgia without previous MVD history (p=0.010, hazard ratio of 0.64). Their probability of remaining pain free at 3, 5, 7 and 10 years was 66.5%, 59.1%, 59.1% and 44.3%, respectively. Twelve patients (34.3%) initially pain free experienced a recurrence with a median delay of 31.21 months (range 3.40-89.93). The hypoesthesia actuarial rate at 1 year was 9.1% and remained stable till 12 years with a median delay of onset of 8 months (range 8-8). Conclusions: Retrogasserian GKS proofed to be safe and effective on the long-term basis even after failed previous MVD. Even if the initial result of pain free was only 77.8%, the toxicity was low with only 9.1% hypoesthesia. No patient reported a bothersome hypoesthesia. The probability of maintaining pain relief in the long-term was of 44.3% at 10 years.

Aplicación para la gestión de un sistema de incidencias de un almacén robotizado

Aquest projecte té com objectiu fer un sistema d’incidències pel control d’un magatzem robotitzat i del cost que comporta la resolució d’aquestes. D’aquesta manera es pretén canviar un mètode de treball rudimentari, passant a un altre totalment estructurat que serveixi per millorar el actual. Per això s’ha creat una aplicació basada en la tecnologia JSF, què permet aconseguir els nostres objectius. L’aplicació inclou una base de dades feta en PostGres SQL on es guardarà tota la informació que s’utilitza en la nostra aplicació. En aquesta memòria s’ha volgut explicar quins han estat els diferents passos que es van donar per poder assolir tots els nostres objectius. En la primera part realitzem una introducció a la situació del problema que es vol solucionar i descriurem els objectius que en hem marcat. Seguidament s’analitzen els requeriments i es detalla com s’implementen les diferents parts de l’aplicació. Per acabar parlem sobre el procés de testing realitzat que ens assegura el correcte funcionament del programa. Resumint, el objectiu principal d’aquest projecte consisteix en crear una eina que a la vegada que facilita la feina dels treballadors del magatzem, serveixi per al control de tot el sistema de treball als directius de l’empresa.

Aplicación de los convenios de la Organización Internacional del Trabajo a través de la jurisprudencia de los tribunales españoles

El presente trabajo de final carrera, como su título indica, “Aplicación de los convenios de la OIT a través de la jurisprudencia de los tribunales españoles”, se ciñe al estudio de la aplicación de los Convenios ratificados por el Estado español en los procesos judiciales que les han sido de aplicación. Los referidos Convenios son, en esencia, tratados internacionales sujetos al régimen jurídico que establece el Derecho Internacional Público y, atendiendo a éste, se rigen por la voluntad de las partes. Cada Estado miembro y firmante, establece el alcance que tendrá cada Convenio, el cual entrará en vigor cuando este Estado receptor lo haya ratificado. Resulta interesante el estudio de las normas de la OIT, principalmente los Convenios, pues son las únicas normas que, una vez ratificadas, tienen el peso de norma sustantiva y los tribunales proceden y deben proceder a su aplicación como tal. De ello, se deduce que existe un mínimo de garantías en el Derecho de Trabajo Internacional, las cuales, afectan a las condiciones laborales de los trabajadores de la mayor parte de los países y como objetivo ambicioso, se debería procurar y conseguir que su aplicación, como norma mínima, fuera en todos los Estados de planeta. Para ello, se realiza un estudio genérico de la aplicación jurisprudencial de los Convenios de la OIT ratificados por España, para finalmente concretar con un Convenio determinado, siendo el mismo, el Convenio número 155, sobre Seguridad y Salud de los Trabajadores y Medio Ambiente de Trabajo, en su aplicación en reclamaciones por daños y perjuicios, así como en recargo de las prestaciones económicas de la Seguridad Social, entre otras, todo ello, derivado de las consecuencias producidas por accidentes de trabajo. Recientemente se ha publicado el instrumento de Ratificación del Convenio número 187, (BOE 04.08.09), sobre el marco promocional para la seguridad y salud en el trabajo, si bien, su entrada en vigor para España será el próximo 5 de mayo de 2010; el mismo, hace hincapié en la importancia de promover de forma continua una cultura nacional de prevención en materia de seguridad y salud, el cual, también tendrá en un futuro su aplicación en el ámbito laboral como norma sustantiva.

Sobre la puesta en marcha del nuevo sistema de financiación regional: proyecciones para 2009 y algunas reflexiones

This paper presents an estimate of the financial results of the new Spanish system of regional financing in 2009. According to these estimates, some regions will experience sharp reductions in their adjusted financing per capita between 2007 and 2009 which may be very difficult to accept. This would mean that there will be strong pressures for the reform of the new system from the very beginning. To avoid, or at least mitigate, this problem it would be helpful to introduce some changes in the bill currently being discussed by the Parliament. The necessary changes would not alter the nucleus of the recent agreement.

Modelado de una cámara de onda milimétrica

En aquest projecte s'ha dissenyat i simulat una càmera d'ones mil·limètriques mitjançant "Spinning Reflectors" amb l'objectiu d'estudiar la qualitat de les imatges obtingudes, així com determinar la configuració de reflectors acceptable per a la nostra càmera. Per al seu disseny, s'ha realitzat el model d'una antena Cassegrain amb botzina alimentadora a FEKO i s'han simulat els diagrames de radiació corresponents als diferents angles de rotació d'ambdós reflectors al voltant de l'eix en el qual estan situats. Finalment, a partir del principi de funcionament de la nostra càmera, s'ha exposat la seva implementació física i s'ha representat en Matlab la seva PSF (Point Spread Function) i la imatge d'un objecte arbitrari d'acord amb les tècniques de formació d'imatges.

Growing up with bilateral hippocampal atrophy: from childhood to teenage.

The respective roles of the medial temporal lobe (MTL) structures in memory are controversial. Some authors put forward a modular account according to which episodic memory and recollection-based processes are crucially dependent on the hippocampal formation whereas semantic acquisition and familiarity-based processes rely on the adjacent parahippocampal gyri. Others defend a unitary view. We report the case of VJ, a boy with developmental amnesia of most likely perinatal onset diagnosed at the age of 8. Magnetic resonance imaging (MRI), including quantitative volumetric measurements of the hippocampal formation and of the entorhinal, perirhinal, and temporopolar cortices, showed severe, bilateral atrophy of the hippocampal formation, fornix and mammillary bodies; by contrast, the perirhinal cortex was within normal range and the entorhinal and temporopolar cortex remained within two standard deviations (SDs) from controls' mean. We examined the development of his semantic knowledge from childhood to teenage as well as his recognition and cued recall memory abilities. On tasks tapping semantic memory, VJ increased his raw scores across years at the same rate as children from large standardisation samples, except for one task; he achieved average performance, consistent with his socio-educational background. He performed within normal range on 74% of recognition tests and achieved average to above average scores on 42% of them despite very severe impairment on 82% of episodic recall tasks. Both faces and landscapes-scenes gave rise to above average scores when tested with coloured stimuli. Cued recall, although impaired, was largely superior to free recall. This case supports a modular account of the MTL with episodic, but not semantic memory depending on the hippocampal formation. Furthermore, the overall pattern of findings is consistent with evidence from both brain-damaged and neuroimaging studies indicating that recollection requires intact hippocampal formation and familiarity relies, at least partly, on the adjacent temporal lobe cortex.

Mejora del medio ambiente y nivel de desarrollo: elementos explicativos de las diferentes opciones en los programas de desarrollo rural (2007-2013) de la Unión Europea

Los programas de desarrollo rural del actual período de programación (2007-13) se han estructurado en 4 ejes. El eje 2 correspondiente a la Mejora del medio ambiente y del entorno rural es, con casi la mitad de los recursos públicos, el principal. El objetivo de este artículo es estudiar los elementos que explican los diferentes niveles de gasto adjudicados a este eje, que oscilan entre el 82,5% y el 25% del gasto público total según Estado Miembro. Se aprecia que el nivel de gasto en el eje 2 está correlacionado con el nivel de renta pero no guarda relación alguna con los indicadores que la Comisión Europea ha establecido en la priorización del la problemática e interés agroambiental de los diferentes territorios europeos.

Helical tomotherapy or intensity-modulated radiation therapy in the treatment of anal cancer: experience of Geneva and Lausanne

Background: To assess the early clinical outcomes and toxicities in patients treated with high precision radiation therapy (RT) consisting of helical tomotherapy (HT) or intensity-modulated radiation therapy (IMRT) for anal cancer. Materials and Methods: Since March 2006, 30 patients with stage I-IIIB anal squamous-cell carcinoma were treated curatively by IMRT or HT alone (n = 2) or by concomitant chemotherapy and IMRT or HT (n = 28). Median age was 59 years (range, 36−83 years) and the female/male ratio was 2.3 (21/9). Primary tumor site was anal canal, anal margin, or both in 26, 1, and 3 patients, respectively. Anal tumor, pelvic and inguinal nodes were irradiated with a median dose of 36 Gy using HT, or 5- or 7-field IMRT in 18 and 12 patients, respectively; After a planned gap of 1−2 weeks (median 1 week), a median boost dose of 23.4 Gwas delivered to the tumor and/or involved nodes using 3DRT (n = 24) or HT/IMRT (n = 6). The total delivered dose ranged between 59.4 and 64.8 Gy (median, 59.4 Gy). Concomitant chemotherapy consisted of mitomycin C alone (n = 1), mitomycin C and 5-fluorouracil (n = 17) or capecitabin (n = 10) in 28 patients. Common Terminology Criteria for Adverse Events v3.0 scale was used to score acute and late toxicities. Results: All but one patient, who developed progressive local and distant disease at the end of RT, achieved a complete response. Twelve months following RT, one patient had a recurrence at the primary tumor site, salvaged with brachytherapy. After a median follow-up of 7.5 months (range, 1−35 months), no deaths were observed. The 2-year actuarial locoregional control and probability of disease control without colostomy rates were 82% and 79%, respectively. RT was well tolerated without any unplanned treatment interruptions. Grade 1 or 2 acute adverse events consisted of skin toxicity in 8 and 22 patients, diarrhea in 18 and 3 patients, and cystitis in 9 and 2 patients; respectively. Only one patient developed grade 3 mucosal necrosis at the end of the treatment, requiring diverting colostomy. No difference in terms of acute toxicity was observed between patients treated with HT or IMRT. None of the 22 patients with a follow-up of more than 3 months developed grade 3 or more late toxicity. Conclusions: Our preliminary results suggest that HT or IMRT combined with concomitant chemotherapy for anal cancer is effective, and associated with favorable rates of toxicity compared with historical series. Further follow-up is warranted to assess late toxicity.

Tackling Violence at Home 09-10 Action Plan

Tackling Violence at Home

Tackling Sexual Violence and Abuse 09-10 Action Plan

Tackling Sexual Violence and Abuse

Statistics on Smoking Cessation Services in Northern Ireland: 08/09: Pre Release Access List

2008/09 Pre-Release Access List