Vemurafenib in patients with BRAF(V600) mutation-positive melanoma with symptomatic brain metastases: final results of an open-label pilot study.

BACKGROUND & AIM: Brain metastases are frequent in patients with metastatic melanoma, indicating poor prognosis. We investigated the BRAF kinase inhibitor vemurafenib in patients with advanced melanoma with symptomatic brain metastases. METHODS: This open-label trial assessed vemurafenib (960mg twice a day) in patients with BRAF(V600) mutation-positive metastatic melanoma with non-resectable, previously treated brain metastases. The primary end-point was safety. Secondary end-points included best overall response rate, and progression-free and overall survival. RESULTS: Twenty-four patients received vemurafenib for a median treatment duration of 3.8 (0.1-11.3) months. The majority of discontinuations were due to disease progression (n=22). Twenty-three of 24 patients reported at least one adverse event (AE). Grade 3 AEs were reported in four (17%; 95% confidence interval [CI], 4.7-37.4%) patients and included cutaneous squamous cell carcinoma in four patients. Median progression-free survival was 3.9 (95% CI, 3.0-5.5) months, and median survival was 5.3 (95% CI, 3.9-6.6) months. An overall partial response (PR) at both intracranial and extracranial sites was achieved in 10 of 24 (42%; 95% CI, 22.1-63.4) evaluable patients, with stable disease in nine (38%; 95% CI, 18.8-59.4) patients. Of 19 patients with measurable intracranial disease, seven (37%) achieved >30% intracranial tumour regression, and three (16%; 95% CI, 3.4-39.6%) achieved a confirmed PR. Other signs of improvement included reduced need for corticosteroids and enhanced performance status. CONCLUSIONS: Vemurafenib can be safely used in patients with advanced symptomatic melanoma that has metastasised to the brain and can result in meaningful tumour regression.

Open source business strategies in the domain of embedded systems

El tema de este estudio es el aumento de la comprensión teórica y empírica de la estrategia de negocio de código abierto en el dominio de sistemas embebidos por investigar modelos de negocios de código abierto, retos, recursos y capacidades operativas y dinámicas.

Open Door Newsletter of the Library, Summer 2006

The Open Door newsletter is produced by the Iowa Commission for the Blind. It is published twice a year with information about the library programs and what is going on.

Open Door Newsletter of the Library, Winter 2003

The Open Door newsletter is produced by the Iowa Commission for the Blind. It is published twice a year with information about the library programs and what is going on.

Open Door Newsletter of the Library, Winter 2003

The Open Door newsletter is produced by the Iowa Commission for the Blind. It is published twice a year with information about the library programs and what is going on.

Open Door Newsletter of the Library, Winter 2004

The Open Door newsletter is produced by the Iowa Commission for the Blind. It is published twice a year with information about the library programs and what is going on.

Open Door Newsletter of the Library, Summer 2004

The Open Door newsletter is produced by the Iowa Commission for the Blind. It is published twice a year with information about the library programs and what is going on.

Open Door Newsletter of the Library, Winter 2005

The Open Door newsletter is produced by the Iowa Commission for the Blind. It is published twice a year with information about the library programs and what is going on.

Open Door Newsletter of the Library, Summer 2005

The Open Door newsletter is produced by the Iowa Commission for the Blind. It is published twice a year with information about the library programs and what is going on.

Open Door Newsletter of the Library, Winter 2006

The Open Door newsletter is produced by the Iowa Commission for the Blind. It is published twice a year with information about the library programs and what is going on.

Investigation of Luther City Council Violation of Open Meetings Law, 2006

Case File 0603454 The Ombudsman received a complaint on August 29, 2006 alleging violations of the Iowa Open Meetings Law by the Luther City Council (Council) in its meeting on August 2, 2006. Based upon my review of the complaint, I identified the following allegations for investigation: • The Council violated Iowa Code section 21.5 by failing to announce the reason session on the August 2, 2006 meeting agenda. • The Council violated Iowa Code section 21.5 by holding a closed session for an impermissible reason. • The Council violated Iowa Code section 21.5(2) by discussing unrelated issues in the closed session.

A new approach in the treatment of high flow native AV fistula: the open-pore external scaffolding prosthesis

Objective: The vascular access steal syndrome is a complication occurring in 1-6% after native arterio-venous (AV) fistulas, often due to huge diameter of the vein. This results in very high flow, which could also be responsible for cardiac overload. The aim of this study is to evaluate the efficiency of a new approach in the treatment of this pathology using open-pore external scaffolding prosthesis.Methods: This a retrospective review of all patients presenting symptomatic high flow after native AV fistula between January 2007 and December 2009 in 3 vascular centers. Pre-operative duplex exam confirmed the diagnosis of high flow. The operation consisted in preparation of the whole fistula, measurement of the flow and section on the venous side. The vein was wrapped with this 6 to 8 mm open-pore external scaffolding prosthesis (ProVena, BBraun, Germany) according to its diameter and to the flow and then sutured. Measurement of the flow was repeated. Patients were followed by duplex exam at 1 week and at 1, 3, 6 and 12 months. Procedural success was defined as complete implantation of the prosthesis and reduction of the flow. Primary outcomes were reduction of the flow and recovery of the symptoms and secondary endpoint was patency of the fistula.Results: During the study period, 14 patients, with a mean age of 65・8 years old, have been operated with this technique.There were 2 native forearmfistulas and 12 on the armwith a mean pre-operative flow of 2600 ml/min (1800-3800). The mode of presentation was pain in 6 patients, neurological disorders in 10 and necrosis in 4. Moreover, 3 patients had cardiac insufficiency due to high flow in the fistula. The procedure was technically successful in 100% of cases. Re-intervention was necessary in 2 patients due to hematoma. Recovery of the initial symptoms occurred in 13 patients (93%). The mean flow reduction was 1200 ml/min (600-2000). In 1 patient, a persistent steal syndrome despite flow reduction to 1400 ml/min resulted in fistula closure 2 months later. At a mean follow-up of 22 months (4-35), all remaining patients (13/14) presented a patent fistula without recurrence.Conclusion: This new approach seems to be safe and effective in the treatment of symptomatic high flow native AV fistulas by significantly reducing the flow and avoiding closure of the vascular access. Longer follow-up with more patients are necessary to evaluate the risk of recurrence.

Sistema de Informação Geográfica na Internet para apoio à gestão de Infra-estruturas, baseado em ferramentas Open Source

A gestão de infra-estruturas é um processo de coordenação, avaliação sistemática e manutenção efectiva das infra-estruturas relacionadas com os serviços básicos. A gestão eficaz de infra-estruturas exige que a disposição dos equipamentos no meio urbano seja conhecida, bem como sua relação com o uso do solo. Sendo a gestão de infra-estruturas uma questão de natureza espacial, é natural pensar na utilização de um Sistema de Informação Geográfica como ferramenta com potencial de grande utilidade, pois permite a georreferenciação de dados espaciais e sua interligação com atributos alfanuméricos, para além da realização de análises complexas e a possibilidade de simular diversos cenários de modo a propiciar uma tomada de decisão eficaz. O elevado custo das licenças e a especificidade de utilização a nível técnico, tornam-se obstáculos na criação e manutenção de dados geográficos. Contudo os recentes desenvolvimentos em tecnologias da Internet têm contribuído para o acesso, publicação, exploração e distribuição da Informação Geográfica. A utilização de SIG distribuídos na Internet (WebGIS), nomeadamente na vertente livre, pode ser uma solução adequada visto que coloca funcionalidades de SIG ao alcance de utilizadores, através de um simples browser, sem necessidade de investimentos em relação a software ou mesmo em formação técnica especializada. Assim, com este projecto pretende-se a criação de um sistema de Informação geográfico na Internet, utilizando softwares livres, que disponibiliza toda a informação geográfica e alfanumérica das infra-estruturas construídas e sob a responsabilidade do Ministério das Infra-estruturas e Economia Marítima, permitindo a visualização e a realização de pesquisas e operações de análise.