999 resultados para re-indexing ULJ
Resumo:
A presença de serviços públicos nos aglomerados populacionais suscita diferentes arti-culações e rearranjos socioterritoriais e promove a sua dinamização e especialização, fomenta a economia local e contribui, direta e indiretamente, para a coesão, o desen-volvimento, a atratividade, a competitividade e a resiliência dos territórios. Nas últimas décadas, as lógicas da oferta e da procura dos serviços públicos têm evoluído rapida-mente, passando de um modelo de gestão fechado e burocrático, para um modelo mais aberto, diversificado, simplificado e participativo. Com elas, surgiram (novos) de-safios na sua gestão, que vão desde a sua sustentabilidade económica até aos impac-tos sociais e territoriais resultantes da modernização, sem esquecer a maior (e cres-cente) exigência do cidadão. Estas mutações têm repercussões na filosofia da sua or-ganização e no modus operandi, com uma crescente orientação para as necessidades da procura e a satisfação do utente, procurando, em simultâneo, reduzir os custos e aumentar a produtividade e a qualidade dos serviços prestados, com base em políticas de inovação e em parcerias e governação em rede. Na prática, estas alterações condu-zem a processos diferenciados, que têm passado pela fusão, reconversão ou mesmo encerramento de serviços públicos. Num contexto de crise económico-financeira, como o que se vive em Portugal, e aten-dendo às mutações ocorridas na oferta e na procura de serviços públicos de educação, saúde, eventos de vida, defesa e segurança e justiça, importa refletir sobre os concei-tos inerentes a estes serviços e sintetizar as principais dinâmicas nesse período de tempo, tendo como pressupostos que, por um lado, o território é um elemento dife-renciador na prestação e na utilização de serviços e que, por outro lado, estes serviços, pela sua natureza estratégica para a sociedade e para a economia, exigem a definição de políticas e de estratégias territoriais consentâneas e inclusivas. Esta investigação centra a sua análise em dois âmbitos geográficos. Numa primeira fa-se, à escala de Portugal continental, onde se obtém um retrato atual da espacialização dos serviços públicos referidos acima. Em seguida, após a criação de uma metodologia inovadora baseada em análises e modelação de informação geográfica para a tipifica-ção dos diferentes tipos de territórios, são identificados três casos de estudo regionais, com características distintas. Assim, são estudados territórios metropolita-nos/densamente urbanizados (constituídos pelos concelhos de Lisboa, Almada, Seixal, Palmela, Sesimbra e Setúbal), eixo urbano-rural (Évora, Portel, Viana do Alentejo, Vidi-gueira, Cuba e Beja) e territórios profundamente rurais (Barrancos, Moura, Serpa e Mértola), para os quais foi realizado um inquérito à população, com o objetivo de compreender a utilização que fazem dos serviços públicos e quais as suas expetativas em relação aos mesmos. Os resultados obtidos para as análises nacional e regionais são acompanhados por uma reflexão sobre a territorialização das políticas de serviços públicos, as quais incidem em matérias relacionadas com o seu planeamento e, sobre-tudo, com a sua gestão.
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PURPOSE OF REVIEW: Amplification and overexpression of the epidermal growth factor receptor (EGFR) gene are a hallmark of primary glioblastoma (45%), making it a prime target for therapy. In addition, these amplifications are frequently associated with oncogenic mutations in the extracellular domain. However, efforts at targeting the EGFR tyrosine kinase using small molecule inhibitors or antibodies have shown disappointing efficacy in clinical trials for newly diagnosed or recurrent glioblastoma. Here, we review recent insights into molecular mechanisms relevant for effective targeting of the EGFR pathway. RECENT FINDINGS: Molecular workup of glioblastoma tissue of patients under treatment with small molecule inhibitors has established drug concentrations in the tumor tissue, and has shed light on the effectiveness of target inhibition and respective effects on pathway signaling. Further, functional analyses of interaction of small molecule inhibitors with distinct properties to bind to the active or inactive form of EGFR have provided new insights that will impact the choice of drugs. Finally, vaccination approaches targeting the EGFRvIII mutant featuring a tumor-specific antigen have shown promising results that warrant larger controlled clinical trials. SUMMARY: A combination of preclinical and clinical studies at the molecular level has provided new insights that will allow refining strategies for targeting the EGFR pathway in glioblastoma.
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BACKGROUND: In patients with outer retinal degeneration, a differential pupil response to long wavelength (red) versus short wavelength (blue) light stimulation has been previously observed. The goal of this study was to quantify differences in the pupillary re-dilation following exposure to red versus blue light in patients with outer retinal disease and compare them with patients with optic neuropathy and with healthy subjects. DESIGN: Prospective comparative cohort study. PARTICIPANTS: Twenty-three patients with outer retinal disease, 13 patients with optic neuropathy and 14 normal subjects. METHODS: Subjects were tested using continuous red and blue light stimulation at three intensities (1, 10 and 100 cd/m2) for 13 s per intensity. Pupillary re-dilation dynamics following the brightest intensity was analysed and compared between the three groups. MAIN OUTCOME MEASURES: The parameters of pupil re-dilation used in this study were: time to recover 90% of baseline size; mean pupil size at early and late phases of re-dilation; and differential re-dilation time for blue versus red light. RESULTS: Patients with outer retinal disease showed a pupil that tended to stay smaller after light termination and thus had a longer time to recovery. The differential re-dilation time was significantly greater in patients with outer retinal disease (median = 28.0 s, P < 0.0001) compared with controls and patients with optic neuropathy. CONCLUSIONS: A differential response of pupil re-dilation following red versus blue light stimulation is present in patients with outer retinal disease but is not found in normal eyes or among patients with visual loss from optic neuropathy.
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Rituximab is an effective treatment of rheumatoid arthritis (RA), which has been approved for the treatment of moderate to severe disease in patients with an inadequate response to anti-TNF therapies. Rituximab differs from other available biological agents for RA by way of its unique mode of action and unrivalled long dosing interval. The efficacy of rituximab subsides progressively over time and re-therapy is generally required to maintain long term disease control. The timing of re-treatment is currently not well established and varies widely in clinical practice. The present document is a concise recommendation regarding re-treatment with rituximab, based on validated outcomes such as the DAS28 and the EULAR response criteria. The recommendation was established through consensus between practitioners familiar with rituximab therapy in RA. Optimisation of the rituximab re-treatment schedule may improve patient outcomes and balance risks and benefits for the individual patient.
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Patients affected with intra-thoracic recurrences of primary or secondary lung malignancies after a first course of definitive radiotherapy have limited therapeutic options, and they are often treated with a palliative intent. Re-irradiation with stereotactic ablative radiotherapy (SABR) represents an appealing approach, due to the optimized dose distribution that allows for high-dose delivery with better sparing of organs at risk. This strategy has the goal of long-term control and even cure. Aim of this review is to report and discuss published data on re-irradiation with SABR in terms of efficacy and toxicity. Results indicate that thoracic re-irradiation may offer satisfactory disease control, however the data on outcome and toxicity are derived from low quality retrospective studies, and results should be cautiously interpreted. As SABR may be associated with serious toxicity, attention should be paid for an accurate patients' selection.