In vitro assessment of the pulmonary toxicity and gastric availability of lead-rich particles from a lead recycling plant

Epidemiological studies in urban areas have linked increasing respiratory and cardiovascular pathologies with atmospheric particulate matter (PM) from anthropic activities. However, the biological fate of metal-rich PM industrial emissions in urban areas of developed countries remains understudied. Lead toxicity and bioaccessibility assessments were therefore performed on emissions from a lead recycling plant, using complementary chemical acellular tests and toxicological assays, as a function of PM size (PM(10-2.5), PM(2.5-1) and PM(1)) and origin (furnace, refining and channeled emissions). Process PM displayed differences in metal content, granulometry, and percentage of inhalable fraction as a function of their origin. Lead gastric bioaccessibility was relatively low (maximum 25%) versus previous studies; although, because of high total lead concentrations, significant metal quantities were solubilized in simulated gastrointestinal fluids. Regardless of origin, the finest PM(1) particles induced the most significant pro-inflammatory response in human bronchial epithelial cells. Moreover, this biological response correlated with pro-oxidant potential assay results, suggesting some biological predictive value for acellular tests. Pulmonary effects from lead-rich PM could be driven by thiol complexation with either lead ions or directly on the particulate surface. Finally, health concern of PM was discussed on the basis of pro-inflammatory effects, accellular test results, and PM size distribution.

The Acute STroke Registry and Analysis of Lausanne (ASTRAL): design and baseline analysis of an ischemic stroke registry including acute multimodal imaging.

BACKGROUND AND PURPOSE: Stroke registries are valuable tools for obtaining information about stroke epidemiology and management. The Acute STroke Registry and Analysis of Lausanne (ASTRAL) prospectively collects epidemiological, clinical, laboratory and multimodal brain imaging data of acute ischemic stroke patients in the Centre Hospitalier Universitaire Vaudois (CHUV). Here, we provide design and methods used to create ASTRAL and present baseline data of our patients (2003 to 2008). METHODS: All consecutive patients admitted to CHUV between January 1, 2003 and December 31, 2008 with acute ischemic stroke within 24 hours of symptom onset were included in ASTRAL. Patients arriving beyond 24 hours, with transient ischemic attack, intracerebral hemorrhage, subarachnoidal hemorrhage, or cerebral sinus venous thrombosis, were excluded. Recurrent ischemic strokes were registered as new events. RESULTS: Between 2003 and 2008, 1633 patients and 1742 events were registered in ASTRAL. There was a preponderance of males, even in the elderly. Cardioembolic stroke was the most frequent type of stroke. Most strokes were of minor severity (National Institute of Health Stroke Scale [NIHSS] score ≤ 4 in 40.8% of patients). Cardioembolic stroke and dissections presented with the most severe clinical picture. There was a significant number of patients with unknown onset stroke, including wake-up stroke (n=568, 33.1%). Median time from last-well time to hospital arrival was 142 minutes for known onset and 759 minutes for unknown-onset stroke. The rate of intravenous or intraarterial thrombolysis between 2003 and 2008 increased from 10.8% to 20.8% in patients admitted within 24 hours of last-well time. Acute brain imaging was performed in 1695 patients (97.3%) within 24 hours. In 1358 patients (78%) who underwent acute computed tomography angiography, 717 patients (52.8%) had significant abnormalities. Of the 1068 supratentorial stroke patients who underwent acute perfusion computed tomography (61.3%), focal hypoperfusion was demonstrated in 786 patients (73.6%). CONCLUSIONS: This hospital-based prospective registry of consecutive acute ischemic strokes incorporates demographic, clinical, metabolic, acute perfusion, and arterial imaging. It is characterized by a high proportion of minor and unknown-onset strokes, short onset-to-admission time for known-onset patients, rapidly increasing thrombolysis rates, and significant vascular and perfusion imaging abnormalities in the majority of patients.

Retinal degeneration progression changes lentiviral vector cell targeting in the retina.

In normal mice, the lentiviral vector (LV) is very efficient to target the RPE cells, but transduces retinal neurons well only during development. In the present study, the tropism of LV has been investigated in the degenerating retina of mice, knowing that the retina structure changes during degeneration. We postulated that the viral transduction would be increased by the alteration of the outer limiting membrane (OLM). Two different LV pseudotypes were tested using the VSVG and the Mokola envelopes, as well as two animal models of retinal degeneration: light-damaged Balb-C and Rhodopsin knockout (Rho-/-) mice. After light damage, the OLM is altered and no significant increase of the number of transduced photoreceptors can be obtained with a LV-VSVG-Rhop-GFP vector. In the Rho-/- mice, an alteration of the OLM was also observed, but the possibility of transducing photoreceptors was decreased, probably by ongoing gliosis. The use of a ubiquitous promoter allows better photoreceptor transduction, suggesting that photoreceptor-specific promoter activity changes during late stages of photoreceptor degeneration. However, the number of targeted photoreceptors remains low. In contrast, LV pseudotyped with the Mokola envelope allows a wide dispersion of the vector into the retina (corresponding to the injection bleb) with preferential targeting of Müller cells, a situation which does not occur in the wild-type retina. Mokola-pseudotyped lentiviral vectors may serve to engineer these glial cells to deliver secreted therapeutic factors to a diseased area of the retina.

Utilização do target costing na determinação do preço de venda: O caso da Alvo, s.a.

Com a crescente competitividade no mundo empresarial, os preços dos produtos passaram a exercer um papel fundamental na expansão e sobrevivência das empresas. Consequentemente, hoje em dia é o mercado que determina o preço de venda de um produto, devendo a empresa produzir ao menor custo possível para garantir o retorno financeiro desejado. O objectivo do trabalho é verificar se os procedimentos de Target Costing podem ser aplicados nas Pequenas e Médias Empresas industriais, em São Vicente, cuja actividade também se destina à produção de produtos alimentícios. Como produto teste foi selecionado o produto A, confecçionado pela empresa Alvo, SA. Para atingirmos os objectivos foram utilizadas várias técnicas e métodos de pesquisa, tais como: levantamento bibliográfico, entrevista, conversas informais, questionário, levantamento de dados nos documentos financeiros da empresa ALVO, SA. Para entendermos e aplicarmos o processo de Target Costing recorreu-se à literatura do mesmo. Foi aplicado um questionário para ver a percepção dos clientes da empresa objecto de estudo, quanto ao preço que considerariam ideal pagar por cada quilograma do produto A adquirida. A entrevista realizada com o director geral da ALVO, SA acompanhada com os dados obtidos do departamento de contabilidade serviram como um meio de conhecer a empresa e o seu funcionamento, realçando informações sobre a fixação do preço venda dos seus produtos, a gestão de custos, entre outros. Antes de testar, através de um caso prático, a aplicação do Target Costing, verificou-se, primeiramente, sua aplicação em termos teóricos, testando os seus princípios e premissas para o produto A, na Empresa ALVO, SA. Como resultado constactou-se que os procedimentos de Target Costing podem ser aplicados, tanto na teoria como na prática, nas Pequenas e Médias Empresas industriais, em São Vicente, cuja actividade se destina a produção do produto A. With the increasing competition in the business world, the prices of products have come to play a key role in the expansion and survival of businesses. Consequently, today the selling price of a product is determined by the market so companies should produce at the lowest possible cost to ensure the desired financial return. The purpose of this paper work is to verify if the Target Costing’s procedure can be applied in small and medium business enterprises in São Vicente, whose activity is production of food. For that, product A was selected for tests. In order to achieve these objectives, some techniques and research methods like bibliographic analysis, interviews, informal conversations, questionnaires and analysis of the financial documents of ALVO, SA that is the subject of this case study, were utilized. With the intention of understanding and applying the Target Costing process we also resorted to a detailed reading of related bibliography. A questionnaire was applied in order to know the customers’ opinions about the ideal price for each kilogram of product A. The interview with the managing director of ALVO, SA, combined with the data obtained in the accounting department, was also used as a way to know the company, and it ’s functioning, highlight ing items such as: selling price format ion, cost management, among other aspects. Before testing, through a practical case study, the use of the Target Costing, the theoretical application was firstly verified by testing its principles and assumptions. Secondly, the application of the Target Costing’s process was shown step by step concerning product A at ALVO SA company. As a result we came to the conclusion that procedures used with Target Costing can be applied, in theory and in practice, in small or medium-sized industrial enterprises, in São Vicente, where product A is being manufactured.

"Leonardi Aretini commentarii de bello punico.

Acquis le 22 avril 1824 de madame Vial avec les mss. latin 11393 et italien 1076, pour le prix global de 100 francs; cf. B.n.F., département des Manuscrits, Archives Modernes 492ter, registre des acquisitions du département des Manuscrits 1821-1830, f. 137 "Leonardi Aretini in commentarios de primo bello punico, un vol. fol."; — ex-libris mutilé d'une main italienne du XVIe s. "Ioannis Baptae [...]" (1)