Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma.

BACKGROUND: Sorafenib (Sb) is a multiple kinase inhibitor targeting both tumour cell proliferation and angiogenesis that may further act as a potent radiosensitizer by arresting cells in the most radiosensitive cell cycle phase. This phase I open-label, noncontrolled dose escalation study was performed to determine the safety and maximum tolerated dose (MTD) of Sb in combination with radiation therapy (RT) and temozolomide (TMZ) in 17 patients with newly diagnosed high-grade glioma. METHODS: Patients were treated with RT (60 Gy in 2 Gy fractions) combined with TMZ 75 mg m(-2) daily, and Sb administered at three dose levels (200 mg daily, 200 mg BID, and 400 mg BID) starting on day 8 of RT. Thirty days after the end of RT, patients received monthly TMZ (150-200 mg m(-2) D1-5/28) and Sb (400 mg BID). Pharmacokinetic (PK) analyses were performed on day 8 (TMZ) and on day 21 (TMZ&Sb) (Clinicaltrials ID: NCT00884416). RESULTS: The MTD of Sb was established at 200 mg BID. Dose-limiting toxicities included thrombocytopenia (two patients), diarrhoea (one patient) and hypercholesterolaemia (one patient). Sb administration did not affect the mean area under the curve(0-24) and mean Cmax of TMZ and its metabolite 5-amino-imidazole-4-carboxamide (AIC). Tmax of both TMZ and AIC was delayed from 0.75 (TMZ alone) to 1.5 h (combined TMZ/Sb). The median progression-free survival was 7.9 months (95% confidence interval (CI): 5.4-14.55), and the median overall survival was 17.8 months (95% CI: 14.7-25.6). CONCLUSIONS: Although Sb can be combined with RT and TMZ, significant side effects and moderate outcome results do not support further clinical development in malignant gliomas. The robust PK data of the TMZ/Sb combination could be useful in other cancer settings.

Assessing the Glaucoma Quality of Life-15 (GCL-15) Questionnaire, Goldmann Tonometry and Moorfields Motion Displacement Test in Glaucoma Case Finding

Purpose: To compare the performance Glaucoma Quality of Life-15 (GQL-15) Questionnaire, intraocular pressure measurement (IOP Goldmann tonometry) and a measure of visual field loss using Moorfields Motion Displacement Test (MDT) in detecting glaucomatous eyes from a self referred population. Methods: The GQL-15 has been suggested to correlate with visual disability and psychophysical measures of visual function in glaucoma patients. The Moorfields MDT is a multi location perimetry test with 32 white line stimuli presented on a grey background on a standard laptop computer. Each stimulus is displaced between computer frames to give the illusion of "apparent motion". Participants (N=312, 90% older than 45 years; 20.5% family history of glaucoma) self referred to an advertised World Glaucoma Day (March 2009) Jules Gonin Eye Hospital, Lausanne Switzerland. Participants underwent a clinical exam (IOP, slit lamp, angle and disc examination by a general ophthalmologist), 90% completed a GQL-15 questionnaire and over 50% completed a MDT test in both eyes. Those who were classified as abnormal on one or more of the following (IOP >21 mmHg/ GQL-15 score >20/ MDT score >2/ clinical exam) underwent a follow up clinical examination by a glaucoma specialist including imaging and threshold perimetry. After the second examination subjects were classified as "healthy"(H), "glaucoma suspect" (GS) (ocular hypertension and/or suspicious disc, angle closure with SD) or "glaucomatous" (G). Results: One hundred and ten subjects completed all 4 initial examinations; of these 69 were referred to complete the 2nd examination and were classified as; 8 G, 24 GS, and 37 H. MDT detected 7/8 G, and 7/24 GS, with false referral rate of 3.8%. IOP detected 2/8 G and 8/24 GS, with false referral rate of 8.9%. GQL-15 detected 4/8 G, 16/24 GS with a false referral rate of 42%. Conclusions: In this sample of participants attending a self referral glaucoma detection event, the MDT performed significantly better than the GQL-15 and IOP in discriminating glaucomatous patients from healthy subjects. Further studies are required to assess the potential of the MDT as a glaucoma screening tool.

Decomposição e liberação de N, P e K de esterco bovino e de cama de frango isolados ou misturados

A utilização de resíduos orgânicos de origem animal na adubação das culturas demanda informações sobre a dinâmica de decomposição e mineralização de nutrientes neles contidos. Este trabalho objetivou avaliar a decomposição e a liberação de N, P e K dos resíduos orgânicos esterco bovino e cama de frango isolados ou misturados, em Argissolo Vermelho-Amarelo, da região de Tabuleiros Costeiros paraibanos. O experimento foi conduzido em delineamento experimental de blocos casualizados, utilizando-se o método das sacolas de decomposição (litterbag), com os tratamentos arranjados em esquema fatorial 3 × 2 × 6, referentes a três resíduos orgânicos: esterco bovino (EB), cama de frango (CF) e a mistura desses resíduos na proporção de 1:1, denominada de esterco misto (EM); duas camadas de incorporação (0-10 e 10-20 cm); e seis períodos de avaliação (0, 30, 90, 150, 210 e 270 dias após a aplicação - DAA) com três repetições. Os resultados revelaram que a profundidade de incorporação não influenciou a decomposição dos resíduos EB e EM, que essa foi mais rápida na CF (0,0035 g dia-1), mais lenta no EB (0,0010 g dia-1) e ocorreu numa velocidade intermediária no EM (0,0020 g dia-1). Houve liberação mais rápida de N no EM (0,0011 g dia-1), de P no EB (0,0040 g dia-1) e de K na CF (0,0025 g dia-1), com tendência de aumento na liberação de N na CF e de P em todos os resíduos com a incorporação desses na camada de 10-20 cm. Após 270 DAP, estimou-se que a liberação de nutrientes pelos resíduos EB, CF e EM, em relação ao teor inicial, foi de 5,0; 15,0; e 28,0 %, para N; 80,0; 68,0; e 47,0 %, para P; e 20,0; 53,0; e 32,0 %, para K. Em valores absolutos, esses percentuais representaram, respectivamente, 19,0; 103,5; e 149,5 kg ha-1 de N; 28,0; 18,0; e 15,0 kg ha-1 de P; e 75,0; 493,0; e 209,0 kg ha-1 de K. Os resíduos orgânicos se evidenciaram fontes inadequadas para suprir isoladamente a demanda nutricional de culturas de ciclo curto nesses solos.

Solubilização Potencial de Fosfatos Mediada pela Microbiota Rizosférica de Eucalipto Cultivado em Topossequência Típica da Zona da Mata Mineira

O uso de fosfatos naturais, aliado ao adequado manejo de microrganismos do solo solubilizadores de fosfato, é uma alternativa para reduzir os custos da adubação fosfatada. No entanto, ambas as práticas requerem a avaliação prévia do potencial da microbiota rizosférica em solubilizar fontes de P pouco reativas em condições de campo. O objetivo deste trabalho foi avaliar o potencial da microbiota do solo de solubilizar os fosfatos de Ca, Fe, Al, além dos fosfatos naturais de Araxá e Catalão em amostras de solo rizosférico e não rizosférico de plantio do hibrido Eucalyptus grandis × E. urophylla, localizados em três pontos de uma topossequência típica da Zona da Mata de Minas Gerais. Adicionalmente, avaliou-se a atividade de fosfatases ácidas e alcalinas sob as mesmas condições experimentais. A microbiota rizosférica das plantas do topo e da baixada apresentou maior potencial de solubilização de fosfato de Ca (5.745,09 e 6.452,80 μg de P, respectivamente), enquanto o solo da encosta não apresentou diferenças entre as fontes inorgânicas testadas. O fosfato de Catalão foi a fonte de fosfato natural com maior potencial de solubilização (1.209,71 μg de P) pela microbiota do solo nas condições avaliadas. O pH final do meio de cultura correlacionou-se negativamente com os valores de P solubilizado, indicando que a acidificação do ambiente foi um dos mecanismos de solubilização utilizados pela microbiota rizosférica in vitro. A atividade das fosfatases ácida e alcalina foi maior na rizosfera de plantas do topo, área com maior teor de matéria orgânica. Não foi observada correlação clara entre o potencial de solubilização de fosfato ou a atividade das fosfatases com o diâmetro médio à altura do peito das árvores do plantio. Este estudo demonstra o efeito da topografia no potencial de solubilização da microbiota do solo, que é influenciada positivamente pelo teor de matéria orgânica do solo.

Solvent vapours in incubators: a source of exposure among neonates?

Hygiene practices in neonatal units require the use of disinfecting solutions containing ethanol or isopropanol. Newly disinfected hands or soaked swabs introduced inside the incubators may emit vapours leading to alcohol exposures to the neonates. Alcohol emissions from hands and other occasional sources (e.g. soaked disinfecting swabs) lead to measurable levels of vapours inside incubators. Average isopropanol and ethanol concentrations ranging from 33.1 to 171.4 mg/m(3) (13.8 to 71.4 ppm) and from 23.5 to more than 146 mg/m3 (9.8 to > 6 ppm) respectively were measured inside occupied incubators (n = 11, measurement time about 230 min) in a neonatal unit of the Centre Hospitalier Universitaire Vaudois in Lausanne during regular activity. Exposure concentrations in a wide range of possible situations were then investigated by modeling using the one-box dispersion model. Theoretical modeling suggested typical isopropanol peaks and average concentrations ranging between 10(2) and 10(3) mg/m(3) (4.10(1) to 4.10(2)ppm), and 10(1) to 10(2) mg/m(3) (4 to 4.10(1) ppm), respectively. Based on our results we suggest several preventive measures to reduce the neonates' exposures to solvent vapours.

Diretrizes curriculares nacionais para o ensino médio: avaliação de documento

Este texto pretende oferecer algumas contribuições para o debate sobre as mudanças propostas pelas Diretrizes Curriculares Nacionais elaboradas para a reforma do ensino médio no Brasil. Na primeira parte, avalia-se o cenário político e econômico, como contexto gerador da última etapa de reformas no âmbito da educação, nos anos 90. Pretende-se questionar a opção por um modelo de reforma de estrutura (no caso brasileiro mais restrita ao Programa de Reforma da Educação Profissionalizante - PROEP) e de currículo, cujos temas encontram justificativa no contexto econômico, social, cultural e político contemporâneo. Discute-se a utilização de um "modelo" que toma por base experiências desenvolvidas em outros países, e por referência teórico-metodológica as orientações internacionais de organismos multilaterais, desconsiderando as peculiaridades e injunções do sistema administrativo-político brasileiro, medida política essa que pode aumentar a tensão e a distância normalmente existentes entre programas de governo e a possibilidade de sua concretude na rede escolar. Na segunda parte, discute-se a Resolução do Conselho Nacional de Educação, da Câmara de Educação Básica, n. 3, de 16.6.98, que institui as Diretrizes Curriculares Nacionais para o ensino médio, bem como as Bases Legais - Parte I - dos Parâmetros Curriculares Nacionais para o Ensino Médio. A análise do discurso oficial toma como referência metodológica a proposição de Bardin (1977, p. 209) para os modelos de análise estrutural, procurando-se relevar os valores implícitos e as conotações dos textos legais

Autoreactive T cells bypass negative selection and respond to self-antigen stimulation during infection.

Central and peripheral tolerance prevent autoimmunity by deleting the most aggressive CD8(+) T cells but they spare cells that react weakly to tissue-restricted antigen (TRA). To reveal the functional characteristics of these spared cells, we generated a transgenic mouse expressing the TCR of a TRA-specific T cell that had escaped negative selection. Interestingly, the isolated TCR matches the affinity/avidity threshold for negatively selecting T cells, and when developing transgenic cells are exposed to their TRA in the thymus, only a fraction of them are eliminated but significant numbers enter the periphery. In contrast to high avidity cells, low avidity T cells persist in the antigen-positive periphery with no signs of anergy, unresponsiveness, or prior activation. Upon activation during an infection they cause autoimmunity and form memory cells. Unexpectedly, peptide ligands that are weaker in stimulating the transgenic T cells than the thymic threshold ligand also induce profound activation in the periphery. Thus, the peripheral T cell activation threshold during an infection is below that of negative selection for TRA. These results demonstrate the existence of a level of self-reactivity to TRA to which the thymus confers no protection and illustrate that organ damage can occur without genetic predisposition to autoimmunity.

Iowa Department of Transportation Major Items - Preliminary Quantity Report, January 16, 2013; With Addendums

Weekly letting report.

Iowa Department of Transportation Major Items - Preliminary Quantity Report, February 19, 2013; With Addendums

Weekly letting report.

Quick Reads, September 18, 2012

IDPH Quick Reads is an electronic newsletter produced by the Director’s Office at the Iowa Department of Public Health. IDPH Quick Reads are published every three to four weeks.

A novel method of dynamic culture surface expansion improves mesenchymal stem cell proliferation and phenotype.

Repeated passaging in conventional cell culture reduces pluripotency and proliferation capacity of human mesenchymal stem cells (MSC). We introduce an innovative cell culture method whereby the culture surface is dynamically enlarged during cell proliferation. This approach maintains constantly high cell density while preventing contact inhibition of growth. A highly elastic culture surface was enlarged in steps of 5% over the course of a 20-day culture period to 800% of the initial surface area. Nine weeks of dynamic expansion culture produced 10-fold more MSC compared with conventional culture, with one-third the number of trypsin passages. After 9 weeks, MSC continued to proliferate under dynamic expansion but ceased to grow in conventional culture. Dynamic expansion culture fully retained the multipotent character of MSC, which could be induced to differentiate into adipogenic, chondrogenic, osteogenic, and myogenic lineages. Development of an undesired fibrogenic myofibroblast phenotype was suppressed. Hence, our novel method can rapidly provide the high number of autologous, multipotent, and nonfibrogenic MSC needed for successful regenerative medicine.

[Voyage en Italie : 1824-1830]. , Eglise Stradone S. Ambrogio : [vue perspective de l'atrium] : [dessin] / h. L. [Henri Labrouste]

Référence bibliographique : Weigert, 209

List of Bid Proposal Holders, May 21, 2013

List of Bid Proposal Holders