Erosividade das chuvas em Uruguaiana, RS, determinada pelo índice EI30, com base no período de 1963 a 1991

A erosividade representa o potencial que as chuvas têm de provocar erosão hídrica no solo. O índice EI30 é um método de determinação dessa erosividade das chuvas e é calculado, para cada chuva individual e erosiva, pelo produto da energia cinética total da chuva e sua intensidade máxima em 30 min. O objetivo deste trabalho foi calcular a erosividade das chuvas do município de Uruguaiana, RS, para subsidiar aplicações práticas em conservação do solo. A partir de pluviogramas diários, foram separados, para cada chuva individual e erosiva, os segmentos com a mesma intensidade, registrados em planilha, digitados e analisados com o programa Chuveros, que calculou o índice EI30. Foram analisadas 978 chuvas erosivas de Uruguaiana, no período de 1963 a 1991, sendo encontrados valores de precipitação média anual de 1.399,8 mm ano-1 e erosividade média anual das chuvas de 8.875 MJ mm ha-1 h-1. Esse é o valor do Fator "R" (erosividade das chuvas) para ser usado na Equação Universal de Perdas de Solo, para predição das perdas de solo por erosão hídrica em Uruguaiana, RS. O período de outubro a abril apresentou 67 e 77,5 % da precipitação e da erosividade anual, respectivamente, sendo por isso necessários maiores cuidados quanto ao manejo dos solos agrícolas. O mês de fevereiro é o de maior potencial erosivo, com 1.403 MJ mm ha-1 h-1. O município de Uruguaiana apresentou 49,2 % do total das chuvas no padrão avançado, 24,5 no padrão intermediário e 26,3 % no padrão atrasado. A erosividade média anual de Uruguaiana pode ser igualada ou superada pelo menos uma vez a cada dois anos. O EI30 médio mensal de Uruguaiana e seu entorno podem ser estimados usando as relações apresentadas com o coeficiente de chuvas, permitindo utilizar dados pluviométricos. O modelo matemático que apresentou a melhor correlação entre o EI30 médio mensal e o coeficiente de chuvas Rc foi o quadrático (r = 0,9948).

Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up.

BACKGROUND: Postmenopausal women with hormone receptor-positive early breast cancer have persistent, long-term risk of breast-cancer recurrence and death. Therefore, trials assessing endocrine therapies for this patient population need extended follow-up. We present an update of efficacy outcomes in the Breast International Group (BIG) 1-98 study at 8·1 years median follow-up. METHODS: BIG 1-98 is a randomised, phase 3, double-blind trial of postmenopausal women with hormone receptor-positive early breast cancer that compares 5 years of tamoxifen or letrozole monotherapy, or sequential treatment with 2 years of one of these drugs followed by 3 years of the other. Randomisation was done with permuted blocks, and stratified according to the two-arm or four-arm randomisation option, participating institution, and chemotherapy use. Patients, investigators, data managers, and medical reviewers were masked. The primary efficacy endpoint was disease-free survival (events were invasive breast cancer relapse, second primaries [contralateral breast and non-breast], or death without previous cancer event). Secondary endpoints were overall survival, distant recurrence-free interval (DRFI), and breast cancer-free interval (BCFI). The monotherapy comparison included patients randomly assigned to tamoxifen or letrozole for 5 years. In 2005, after a significant disease-free survival benefit was reported for letrozole as compared with tamoxifen, a protocol amendment facilitated the crossover to letrozole of patients who were still receiving tamoxifen alone; Cox models and Kaplan-Meier estimates with inverse probability of censoring weighting (IPCW) are used to account for selective crossover to letrozole of patients (n=619) in the tamoxifen arm. Comparison of sequential treatments to letrozole monotherapy included patients enrolled and randomly assigned to letrozole for 5 years, letrozole for 2 years followed by tamoxifen for 3 years, or tamoxifen for 2 years followed by letrozole for 3 years. Treatment has ended for all patients and detailed safety results for adverse events that occurred during the 5 years of treatment have been reported elsewhere. Follow-up is continuing for those enrolled in the four-arm option. BIG 1-98 is registered at clinicaltrials.govNCT00004205. FINDINGS: 8010 patients were included in the trial, with a median follow-up of 8·1 years (range 0-12·4). 2459 were randomly assigned to monotherapy with tamoxifen for 5 years and 2463 to monotherapy with letrozole for 5 years. In the four-arm option of the trial, 1546 were randomly assigned to letrozole for 5 years, 1548 to tamoxifen for 5 years, 1540 to letrozole for 2 years followed by tamoxifen for 3 years, and 1548 to tamoxifen for 2 years followed by letrozole for 3 years. At a median follow-up of 8·7 years from randomisation (range 0-12·4), letrozole monotherapy was significantly better than tamoxifen, whether by IPCW or intention-to-treat analysis (IPCW disease-free survival HR 0·82 [95% CI 0·74-0·92], overall survival HR 0·79 [0·69-0·90], DRFI HR 0·79 [0·68-0·92], BCFI HR 0·80 [0·70-0·92]; intention-to-treat disease-free survival HR 0·86 [0·78-0·96], overall survival HR 0·87 [0·77-0·999], DRFI HR 0·86 [0·74-0·998], BCFI HR 0·86 [0·76-0·98]). At a median follow-up of 8·0 years from randomisation (range 0-11·2) for the comparison of the sequential groups with letrozole monotherapy, there were no statistically significant differences in any of the four endpoints for either sequence. 8-year intention-to-treat estimates (each with SE ≤1·1%) for letrozole monotherapy, letrozole followed by tamoxifen, and tamoxifen followed by letrozole were 78·6%, 77·8%, 77·3% for disease-free survival; 87·5%, 87·7%, 85·9% for overall survival; 89·9%, 88·7%, 88·1% for DRFI; and 86·1%, 85·3%, 84·3% for BCFI. INTERPRETATION: For postmenopausal women with endocrine-responsive early breast cancer, a reduction in breast cancer recurrence and mortality is obtained by letrozole monotherapy when compared with tamoxifen montherapy. Sequential treatments involving tamoxifen and letrozole do not improve outcome compared with letrozole monotherapy, but might be useful strategies when considering an individual patient's risk of recurrence and treatment tolerability. FUNDING: Novartis, United States National Cancer Institute, International Breast Cancer Study Group.

Single-step extraction of fluconazole from plasma by ultra-filtration for the measurement of its free concentration by high performance liquid chromatography.

High performance liquid chromatography (HPLC) is the reference method for measuring concentrations of antimicrobials in blood. This technique requires careful sample preparation. Protocols using organic solvents and/or solid extraction phases are time consuming and entail several manipulations, which can lead to partial loss of the determined compound and increased analytical variability. Moreover, to obtain sufficient material for analysis, at least 1 ml of plasma is required. This constraint makes it difficult to determine drug levels when blood sample volumes are limited. However, drugs with low plasma-protein binding can be reliably extracted from plasma by ultra-filtration with a minimal loss due to the protein-bound fraction. This study validated a single-step ultra-filtration method for extracting fluconazole (FLC), a first-line antifungal agent with a weak plasma-protein binding, from plasma to determine its concentration by HPLC. Spiked FLC standards and unknowns were prepared in human and rat plasma. Samples (240 microl) were transferred into disposable microtube filtration units containing cellulose or polysulfone filters with a 5 kDa cut-off. After centrifugation for 60 min at 15000g, FLC concentrations were measured by direct injection of the filtrate into the HPLC. Using cellulose filters, low molecular weight proteins were eluted early in the chromatogram and well separated from FLC that eluted at 8.40 min as a sharp single peak. In contrast, with polysulfone filters several additional peaks interfering with the FLC peak were observed. Moreover, the FLC recovery using cellulose filters compared to polysulfone filters was higher and had a better reproducibility. Cellulose filters were therefore used for the subsequent validation procedure. The quantification limit was 0.195 mgl(-1). Standard curves with a quadratic regression coefficient > or = 0.9999 were obtained in the concentration range of 0.195-100 mgl(-1). The inter and intra-run accuracies and precisions over the clinically relevant concentration range, 1.875-60 mgl(-1), fell well within the +/-15% variation recommended by the current guidelines for the validation of analytical methods. Furthermore, no analytical interference was observed with commonly used antibiotics, antifungals, antivirals and immunosuppressive agents. Ultra-filtration of plasma with cellulose filters permits the extraction of FLC from small volumes (240 microl). The determination of FLC concentrations by HPLC after this single-step procedure is selective, precise and accurate.

mTORC2 regulates PGE(2)-mediated endothelial cell survival and migration

Prostaglandin E-2 (PGE(2)) promotes angiogenesis by in part inducing endothelial cell survival and migration. The present study examined the role of mTOR and its two complexes, mTORC1 and mTORC2, in PGE(2)-mediated endothelial cell responses. We used small interfering RNA (siRNA) to raptor or rictor to block mTORC1 or mTORC2, respectively. We observed that down-regulation of mTORC2 but not mTORC1 reduced baseline and PGE(2)-induced endothelial cell survival and migration. At the molecular level, we found that knockdown of mTORC2 inhibited PGE2-mediated Rac and Akt activation two important signaling intermediaries in endothelial cell migration and survival, respectively. In addition, inhibition of mTORC2 by prolonged exposure of endothelial cells to rapamycin also prevented PGE2-mediated endothelial cell survival and migration confirming the results obtained with the siRNA approach. Taken together these results show that mTORC2 but not mTORC1 is an important signaling intermediary in PGE2-mediated endothelial cell responses.

Encapsulated, genetically engineered cells, secreting glucagon-like peptide-1 for the treatment of non-insulin-dependent diabetes mellitus.

Non-insulin-dependent, or type II, diabetes mellitus is characterized by a progressive impairment of glucose-induced insulin secretion by pancreatic beta cells and by a relative decreased sensitivity of target tissues to the action of this hormone. About one third of type II diabetic patients are treated with oral hypoglycemic agents to stimulate insulin secretion. These drugs however risk inducing hypoglycemia and, over time, lose their efficacy. An alternative treatment is the use of glucagon-like peptide-1 (GLP-1), a gut peptidic hormone with a strong insulinotropic activity. Its activity depends of the presence of normal blood glucose concentrations and therefore does not risk inducing hypoglycemia. GLP-1 can correct hyperglycemia in diabetic patients, even in those no longer responding to hypoglycemic agents. Because it is a peptide, GLP-1 must be administered by injection; this may prevent its wide therapeutic use. Here we propose to use cell lines genetically engineered to secrete a mutant form of GLP-1 which has a longer half-life in vivo but which is as potent as the wild-type peptide. The genetically engineered cells are then encapsulated in semi-permeable hollow fibers for implantation in diabetic hosts for constant, long-term, in situ delivery of the peptide. This approach may be a novel therapy for type II diabetes.

The role of epilepsy in early language development in a child with a congenital lesion in the right hemisphere

Early epilepsy is known to worsen the developmental prognosis of young children with a congenital focal brain lesion, but its direct role is often very difficult to delineate from the other variables. This requires prolonged periods of follow-up with simultaneous serial electrophysiological and developmental assessments which are rarely obtained. We studied a male infant with a right prenatal infarct in the territory of the right middle cerebral artery resulting in a left spastic hemiparesis, and an epileptic disorder (infantile spasms with transient right hemihypsarrhythmia and focal seizures) from the age of 7 months until the age of 4 years. Pregnancy and delivery were normal. A dissociated delay of early language acquisition affecting mainly comprehension without any autistic features was documented. This delay was much more severe than usually expected in children with early focal lesions, and its evolution, with catch-up to normal, was correlated with the active phase of the epilepsy. We postulate that the epilepsy specifically amplified a pattern of delayed language emergence, mainly affecting lexical comprehension, reported in children with early right hemisphere damage.

Associação de deltametrina com Acarophenax lacunatus e seu impacto sobre o desenvolvimento de Rhyzopertha dominica

O objetivo deste trabalho foi avaliar a associação do inseticida deltametrina, aplicado em grãos de trigo, com o ácaro parasita Acarophenax lacunatus e seu impacto sobre o desenvolvimento de Rhyzopertha dominica. Grãos de trigo (13% de teor de água) foram tratados com diferentes doses de deltametrina (0,00, 0,125, 0,25, 0,375, 0,50, 0,625, 0,75, 0,875 e 1,00 mg i.a. kg-1). As unidades experimentais consistiram de placas de Petri contendo 30 g de grãos tratados, ou não, com o inseticida, infestados com 30 adultos de R. dominica. Cinco dias depois da infestação, foram inoculados cinco ácaros parasitas por unidade experimental, em sete repetições. As unidades experimentais foram armazenadas por 60 dias depois da infestação em câmara climatizada ajustada a 30±1°C, 60±5% UR e escotofase de 24 horas. A taxa instantânea de crescimento de R. dominica apresentou índices negativos para as doses de deltametrina maiores que 0,25 mg i.a. kg-1. A. lacunatus associado a doses de deltametrina menores que 0,5 mg i.a. kg-1 reduz as fases imaturas de R. dominica.

Heavy Agricultural Loads on Pavements and Bridges, HR-1073, 1999

During the harvest season in Iowa, it is common to have single axle loads on secondary roads and bridges that are excessive (typical examples are grain carts) and well beyond normal load limits. Even though these excessive loads occur only during a short time of the year, they may do significant damage to pavements and bridges. In addition, the safety of some bridges may be compromised because of the excessive loads, and sometimes there may be little indication to the users that damage may be imminent. At this time there are no Iowa laws regulating axle loads allowed for agricultural equipment. This study looks at the potential problems this may cause on secondary roads and timber stringer bridges. Both highway pavement and timber bridges are evaluated in this report. A section (panel) of Iowa PCC paved county road was chosen to study the effects of heavy agricultural loads on pavements. Instrumentation was applied to the panel and a heavily loaded grain cart was rolled across. The collected data were analyzed for any indication of excessive stresses of the concrete. The second study, concerning excessive loads on timber stringer bridges, was conducted in the laboratory. Four bridge sections were constructed and tested. Two of the sections contained five stringers and two sections had three stringers. Timber for the bridges came from a dismantled bridge, and deck panels were cut from new stock. All timber was treated with creosote. A hydraulic load was applied at the deck mid-span using a foot print representing a tire from a typical grain cart. Force was applied until failure of the system resulted. The collected data were evaluated to provide indications of load distribution and for comparison with expected wheel loads for a typical heavily loaded single axle grain cart. Results of the pavement tests showed that the potential of over-stressing the pavement is a possibility. Even though most of the tension stress levels recorded were below the rupture strength of the concrete, there were a few instances where the indicated tension stress level exceeded the concrete rupture strength. Results of the bridge tests showed that when the static ultimate load capacity of the timber stringer bridge sections was reached, there was sudden loss of capacity. Prior to reaching this ultimate capacity, the load sharing between the stringers was very uniform. The failure was characterized by loss of flexural capacity of the stringers. In all tests, the ultimate test load exceeded the wheel load that would be applied by an 875 bushel single axle grain cart.

Examen des principes de la constitution civile du clergé, ou du Réglement décrété par l'Assemblée nationale de France sur les formes extérieures du culte catholique ([Reprod.]) / par M. l'Evêque de Viviers

Collection : Les archives de la Révolution française ; 8.875

Impacts of climate change on Swiss biodiversity: An indicator taxa approach

We present a new indicator taxa approach to the prediction of climate change effects on biodiversity at the national level in Switzerland. As indicators, we select a set of the most widely distributed species that account for 95% of geographical variation in sampled species richness of birds, butterflies, and vascular plants. Species data come from a national program designed to monitor spatial and temporal trends in species richness. We examine some opportunities and limitations in using these data. We develop ecological niche models for the species as functions of both climate and land cover variables. We project these models to the future using climate predictions that correspond to two IPCC 3rd assessment scenarios for the development of 'greenhouse' gas emissions. We find that models that are calibrated with Swiss national monitoring data perform well in 10-fold cross-validation, but can fail to capture the hot-dry end of environmental gradients that constrain some species distributions. Models for indicator species in all three higher taxa predict that climate change will result in turnover in species composition even where there is little net change in predicted species richness. Indicator species from high elevations lose most areas of suitable climate even under the relatively mild B2 scenario. We project some areas to increase in the number of species for which climate conditions are suitable early in the current century, but these areas become less suitable for a majority of species by the end of the century. Selection of indicator species based on rank prevalence results in a set of models that predict observed species richness better than a similar set of species selected based on high rank of model AUC values. An indicator species approach based on selected species that are relatively common may facilitate the use of national monitoring data for predicting climate change effects on the distribution of biodiversity.