A compartmental model of hepatic disposition kinetics: 1. Model development and application to linear kinetics

The conventional convection-dispersion model is widely used to interrelate hepatic availability (F) and clearance (Cl) with the morphology and physiology of the liver and to predict effects such as changes in liver blood flow on F and Cl. The extension of this model to include nonlinear kinetics and zonal heterogeneity of the liver is not straightforward and requires numerical solution of partial differential equation, which is not available in standard nonlinear regression analysis software. In this paper, we describe an alternative compartmental model representation of hepatic disposition (including elimination). The model allows the use of standard software for data analysis and accurately describes the outflow concentration-time profile for a vascular marker after bolus injection into the liver. In an evaluation of a number of different compartmental models, the most accurate model required eight vascular compartments, two of them with back mixing. In addition, the model includes two adjacent secondary vascular compartments to describe the tail section of the concentration-time profile for a reference marker. The model has the added flexibility of being easy to modify to model various enzyme distributions and nonlinear elimination. Model predictions of F, MTT, CV2, and concentration-time profile as well as parameter estimates for experimental data of an eliminated solute (palmitate) are comparable to those for the extended convection-dispersion model.

Cationic drug pharmacokinetics in diseased livers determined by fibrosis index, hepatic protein content, microsomal activity, and nature of drug

The disposition kinetics of six cationic drugs in perfused diseased and normal rat livers were determined by multiple indicator dilution and related to the drug physicochemical properties and liver histopathology. A carbon tetrachloride (CCl4)induced acute hepatocellular injury model had a higher fibrosis index (FI), determined by computer-assisted image analysis, than did an alcohol-induced chronic hepatocellular injury model. The alcohol-treated group had the highest hepatic alpha(1)- acid glycoprotein, microsomal protein (MP), and cytochrome P450 (P450) concentrations. Various pharmacokinetic parameters could be related to the octanol-water partition coefficient (log P-app) of the drug as a surrogate for plasma membrane partition coefficient and affinity for MP or P450, the dependence being lower in the CCl4-treated group and higher in the alcohol-treated group relative to controls. Stepwise regression analysis showed that hepatic extraction ratio, permeability-surface area product, tissue-binding constant, intrinsic clearance, partition ratio of influx (k(in)) and efflux rate constant (k(out)), and k(in)/k(out) were related to physicochemical properties of drug (log P-app or pK(a)) and liver histopathology (FI, MP, or P450). In addition, hepatocyte organelle ion trapping of cationic drugs was evident in all groups. It is concluded that fibrosis-inducing hepatic disease effects on cationic drug disposition in the liver may be predicted from drug properties and liver histopathology.

Catheter effects in organ perfusion experiments

In a typical isolated organ perfusion experiment, a substance is injected upstream of an organ and then collected at some distance downstream. To reach the organ from the injection site, and then from the organ to the collector, a solute passes through catheters, usually tubes with circular cross-sections. Catheters cause distortion to the concentration-time profile of the perfusion. In this paper, we analyse catheter distribution kinetics from a mathematical point of view, develop the function most suitable for modeling this distribution and successfully apply this function to experimental data. (C) 2002 Academic Press.

Routine ultrasound screening in diabetic pregnancies

Objectives To assess the detection rate of congenital fetal malformations and specific problems related to routine ultrasound screening in women with pre-existing diabetes. Methods A retrospective study was carried out to assess the performance of routine ultrasound screening in women with pre-existing diabetes (Types 1 and 2) within a tertiary institution. The incidence, type and risk factors for congenital fetal malformations were determined. The detection rate of fetal anomalies for diabetic women was compared with that for the low-risk population. Factors affecting these detection rates were evaluated. Results During the study period, 12 169 low-risk pregnant women and 130 women with pre-existing diabetes had routine ultrasound screening performed within the institution. A total of 10 major anomalies (7.7%) and three minor anomalies (2.3%) were present in the fetuses of the diabetic women. Central nervous system and cardiovascular system anomalies accounted for 60% of the major anomalies. Peri-conceptional hemoglobin A 1 c of more than 9% was associated with a high prevalence of major anomalies (14311000). Women who had fetuses with major anomalies bad a significantly higher incidence of obesity (78% vs. 37%; P < 0.05). Ultrasound examination of these diabetic pregnancies showed high incidences of suboptimal image quality (37%), incomplete examinations, and repeat examinations (17%). Compared to the 'low-risk' non-diabetic population from the same institution, the relative risk for a major congenital anomaly among the diabetic women was 5.9-fold higher (95% confidence interval, 2.9-11.9). The detection rate for major fetal anomalies was significantly lower for diabetic women (30% vs. 73%; P < 0.01), and the mean body mass index for the diabetic group was significantly higher (29 vs. 23 kg/m(2); P < 0.001). Conclusion The incidence of congenital anomalies is higher in diabetic pregnancies. Unfortunately, the detection rate for fetal anomalies by antenatal ultrasound scan was significantly, worse than that for the low-risk population. This is likely to be related to the maternal body habitus and unsatisfactory examinations. Methods to overcome these difficulties are discussed.

delta N-15 values of tropical savanna and monsoon forest species reflect root specialisations and soil nitrogen status

A large number of herbaceous and woody plants from tropical woodland, savanna, and monsoon forest were analysed to determine the impact of environmental factors (nutrient and water availability, fire) and biological factors (microbial associations, systematics) on plant delta(15)N values. Foliar delta(15)N values of herbaceous and woody species were not related to growth form or phenology, but a strong relationship existed between mycorrhizal status and plant delta(15)N. In woodland and savanna, woody species with ectomycorrhizal (ECM) associations and putative N-2-fixing species with ECM/arbuscular (AM) associations had lowest foliar delta(15)N values (1.0-0.6parts per thousand), AM species had mostly intermediate delta(15)N values (average +0.6parts per thousand), while non-mycorrhizal Proteaceae had highest delta(15)N values (+2.9 to +4.1parts per thousand). Similar differences in foliar delta(15)N were observed between AM (average 0.1 and 0.2parts per thousand) and non-mycorrhizal (average +0.8 and +0.3parts per thousand) herbaceous species in woodland and savanna. Leguminous savanna species had significantly higher leaf N contents (1.8-2.5% N) than non-fixing species (0.9-1.2% N) indicating substantial N acquisition via N-2 fixation. Monsoon forest species had similar leaf N contents (average 2.4% N) and positive delta(15)N values (+0.9 to +2.4parts per thousand). Soil nitrification and plant NO3- use was substantially higher in monsoon forest than in woodland or savanna. In the studied communities, higher soil N content and nitrification rates were associated with more positive soil delta(15)N and plant delta(15)N. In support of this notion, Ficus, a high NO3- using taxa associated with NO3- rich sites in the savanna, had the highest delta(15)N values of all AM species in the savanna. delta(15)N of xylem sap was examined as a tool for studying plant delta(15)N relations. delta(15)N of xylem sap varied seasonally and between differently aged Acacia and other savanna species. Plants from annually burnt savanna had significantly higher delta(15)N values compared to plants from less frequently burnt savanna, suggesting that foliar N-15 natural abundance could be used as marker for assessing historic fire regimes. Australian woodland and savanna species had low leaf delta(15)N and N content compared to species from equivalent African communities indicating that Australian biota are the more N depauperate. The largest differences in leaf delta(15)N occurred between the dominant ECM Australian and African savanna (miombo) species, which were depleted and enriched in N-15, respectively. While the depleted delta(15)N of Australian ECM species are similar to those of previous reports on ECM species in natural plant communities, the N-15-enriched delta(15)N of African ECM species represent an anomaly.

Developmental anomalies in the tooth plates and jaw bones of lungfish

Lungfish of the tooth-plated lineage, both fossil and living, may be affected by alterations in the permanent tooth plates and associated jaw bones as they grow. In a few taxa, the unusual structures may be so common that they must be considered as normal for those species, or as a variation of the normal condition. In others the condition is rare, affecting only a few individuals. Variations, or anomalies, may appear in the growing tissues of the lungfish tooth plate at any time in the life cycle, although they usually appear early in development. Once the changes appear, they persist in the dentition. The altered structures include divided or intercalated ridges, short ridge anomaly, changes in the shape, number and position of cusps, pattern loss, and fused ridges or cusps. Criteria used to distinguish alteration from normal conditions are the incidence of the character in the population, the associated changes in the jaw bone, and the position of the altered structure in the tooth plate. The occurrence of similar changes across a wide range of different species suggests that they may have a genetic cause, especially when they are a rare occurrence in most taxa, but common enough to be a part of the normal variation in others. Prevalence of related anomalies throughout the history of the group suggests that dipnoans of the tooth-plated lineage are closely related, despite significant differences in morphology, microstructure, and function of the denfitions.

Complicações perinatais no Hospital Universitário Cassiano Antonio de Moraes: uma questão de idade?

A população brasileira vem passando por uma transição demográfica e epidemiológica, caracterizadas por aumento na expectativa de vida, diminuições nas taxas de mortalidade, natalidade e fecundidade, aumento da escolaridade, diminuição do desemprego, aumento das enfermidades crônico-degenerativas e diminuição das enfermidades infectocontagiosas. Tais transições vêm afetando também a perinatologia, com aumento proporcional e absoluto das gestações tardias tanto no Espírito Santo quanto no Brasil. Este estudo realizou uma análise retrospectiva das gestações tardias no HUCAM, comparando as mesmas com as gestações de mulheres adolescentes e adultas jovens quanto aos seguintes desfechos perinatais: anomalia fetal, hipóxia no primeiro e quinto minuto de vida, duração da gestação, peso ao nascer e tipo de parto. As variáveis foram analisadas categoricamente, e comparadas através de análise bivariada, utilizando-se o Teste Exato de Fisher, e através de regressão logística. Na análise bivariada, foi encontrada apenas associação entre a idade materna e o tipo de parto, mas esta associação não foi confirmada na regressão logística. Analisando outros fatores relativos à gestação, restou evidenciado uma associação positiva entre um menor número de consultas pré-natais e uma maior frequência de hipóxia no recém-nascido e de prematuridade (odds ratio de 2,9 e 5,7, respectivamente). Ao final deste trabalho são elaboradas propostas para aprimoramento da coleta e do armazenamento de dados acerca da gestação no HUCAM, e para otimização da assistência pré-natal das gestantes atendidas pelo hospital, visando melhorar os desfechos perinatais encontrados.

Stratification of the earth beneath the Azores from P and S receiver functions

Seismic recordings of IRIS/IDA/GSN station CMLA and of several temporary stations in the Azores archipelago are processed with P and S receiver function (PRF and SRF) techniques. Contrary to regional seismic tomography these methods provide estimates of the absolute velocities and of the Vp/Vs ratio up to a depth of similar to 300 km. Joint inversion of PRFs and SRFs for a few data sets consistently reveals a division of the subsurface medium into four zones with a distinctly different Vp/Vs ratio: the crust similar to 20 km thick with a ratio of similar to 1.9 in the lower crust, the high-Vs mantle lid with a strongly reduced VpNs velocity ratio relative to the standard 1.8, the low-velocity zone (LVZ) with a velocity ratio of similar to 2.0, and the underlying upper-mantle layer with a standard velocity ratio. Our estimates of crustal thickness greatly exceed previous estimates (similar to 10 km). The base of the high-Vs lid (the Gutenberg discontinuity) is at a depth of-SO km. The LVZ with a reduction of S velocity of similar to 15% relative to the standard (IASP91) model is terminated at a depth of similar to 200 km. The average thickness of the mantle transition zone (TZ) is evaluated from the time difference between the S410p and SKS660p, seismic phases that are robustly detected in the S and SKS receiver functions. This thickness is practically similar to the standard IASP91 value of 250 km. and is characteristic of a large region of the North Atlantic outside the Azores plateau. Our data are indicative of a reduction of the S-wave velocity of several percent relative to the standard velocity in a depth interval from 460 to 500 km. This reduction is found in the nearest vicinities of the Azores, in the region sampled by the PRFs, but, as evidenced by SRFs, it is missing at a distance of a few hundred kilometers from the islands. We speculate that this anomaly may correspond to the source of a plume which generated the Azores hotspot. Previously, a low S velocity in this depth range was found with SRF techniques beneath a few other hotspots.

From unthinned continent to ocean: The deep structure of the West Iberia passive continental margin at 38 degrees N

The crustal and lithospheric mantle structure at the south segment of the west Iberian margin was investigated along a 370 km long seismic transect. The transect goes from unthinned continental crust onshore to oceanic crust, crossing the ocean-continent transition (OCT) zone. The wide-angle data set includes recordings from 6 OBSs and 2 inland seismic stations. Kinematic and dynamic modeling provided a 2D velocity model that proved to be consistent with the modeled free-air anomaly data. The interpretation of coincident multi-channel near-vertical and wide-angle reflection data sets allowed the identification of four main crustal domains: (i) continental (east of 9.4 degrees W); (ii) continental thinning (9.4 degrees W-9.7 degrees W): (iii) transitional (9.7 degrees W-similar to 10.5 degrees W); and (iv) oceanic (west of similar to 10.5 degrees W). In the continental domain the complete crustal section of slightly thinned continental crust is present. The upper (UCC, 5.1-6.0 km/s) and the lower continental crust (LCC, 6.9-7.2 km/s) are seismically reflective and have intermediate to low P-wave velocity gradients. The middle continental crust (MCC, 6.35-6.45 km/s) is generally unreflective with low velocity gradient. The main thinning of the continental crust occurs in the thinning domain by attenuation of the UCC and the LCC. Major thinning of the MCC starts to the west of the LCC pinchout point, where it rests directly upon the mantle. In the thinning domain the Moho slope is at least 13 degrees and the continental crust thickness decreases seaward from 22 to 11 km over a similar to 35 km distance, stretched by a factor of 1.5 to 3. In the oceanic domain a two-layer high-gradient igneous crust (5.3-6.0 km/s; 6.5-7.4 km/s) was modeled. The intra-crustal interface correlates with prominent mid-basement, 10-15 km long reflections in the multi-channel seismic profile. Strong secondary reflected PmP phases require a first order discontinuity at the Moho. The sedimentary cover can be as thick as 5 km and the igneous crustal thickness varies from 4 to 11 km in the west, where the profile reaches the Madeira-Tore Rise. In the transitional domain the crust has a complex structure that varies both horizontally and vertically. Beneath the continental slope it includes exhumed continental crust (6.15-6.45 km/s). Strong diffractions were modeled to originate at the lower interface of this layer. The western segment of this transitional domain is highly reflective at all levels, probably due to dykes and sills, according to the high apparent susceptibility and density modeled at this location. Sub-Moho mantle velocity is found to be 8.0 km/s, but velocities smaller than 8.0 km/s confined to short segments are not excluded by the data. Strong P-wave wide-angle reflections are modeled to originate at depth of 20 km within the lithospheric mantle, under the eastern segment of the oceanic domain, or even deeper at the transitional domain, suggesting a layered structure for the lithospheric mantle. Both interface depths and velocities of the continental section are in good agreement to the conjugate Newfoundland margin. A similar to 40 km wide OCT having a geophysical signature distinct from the OCT to the north favors a two pulse continental breakup.

Levantamento de anomalias nos sistemas impermeabilizantes de coberturas planas

As coberturas planas são um dos principais elementos construtivos de uma edificação, necessitando por isso de materiais com qualidade e certificados por organismos competentes, bem como de uma conceção e execução minuciosas. Em Portugal, os estudos sobre as anomalias realmente observadas em coberturas planas são ainda bastante reduzidos. Nesse âmbito, o presente trabalho teve como objetivo, efetuar o levantamento e a análise estatística das principais anomalias e causas identificadas em coberturas planas de 75 edifícios, permitindo assim a elaboração de um estudo que possa contribuir para a prevenção dessas anomalias e que indique também as medidas necessárias à reparação e os respetivos custos associados. As anomalias foram analisadas através da observação "in situ" das coberturas o que conduziu ao preenchimento de fichas de obra com os dados recolhidos. Da análise estatística efetuada aos edifícios, verificou-se que as principais anomalias detetadas estão relacionadas com perfurações e fissurações do sistema impermeabilizante, resultantes da falta de conhecimento dos utilizadores. Foi possível verificar erros de execução de remates em pontos singulares da cobertura, por falta de pormenores construtivos desses pontos ou erros de execução por parte do aplicador. Em muitos dos casos estudados, não foi detetada nenhuma anomalia, porque se considerou razoável considerar que o sistema impermeabilizante tenha atingido o fim de vida útil. O custo médio por metro quadrado associado à reabilitação de uma cobertura plana é influenciado principalmente por dois fatores: área e acessibilidade da cobertura. O tipo de anomalia e/ou a sua causa não determinaram o custo por metro quadrado da reparação efetuada, pois esta foi sempre de caracter integral e nunca pontual.

Segurança contra intrusão em redes informáticas

Devido ao facto de hoje em dia a informação que é processada numa rede informática empresarial, ser cada vez mais de ordem confidencial, torna-se necessário que essa informação esteja o mais protegida possível. Ao mesmo tempo, é necessário que esta a informação esteja disponível com a devida rapidez, para os parceiros certos, num mundo cada vez mais globalizado. Com este trabalho pretende-se efectuar o estudo e implementação da segurança, numa pequena e genérica rede de testes, que facilmente seja extrapolada, para uma rede da dimensão, de uma grande empresa com potenciais ramificações por diversos locais. Pretende-se implementar/monitorização segurança quer externamente, (Internet service provider ISP) quer internamente (activos de rede, postos de trabalho/utilizadores). Esta análise é baseada na localização (local, wireless ou remota), e, sempre que seja detectada qualquer anomalia, seja identificada a sua localização, sendo tomadas automaticamente acções de protecção. Estas anomalias poderão ser geridas recorrendo a ferramentas open source ou comerciais, que façam a recolha de toda a informação necessária, e tomem acções de correcção ou alerta mediante o tipo de anomalia.

Seismic imaging of the western Iberian crust using ambient noise: Boundaries and internal structure of the Iberian Massif

We present new Rayleigh-wave dispersion maps of the western Iberian Peninsula for periods between 8 and 30 s, obtained from correlations of seismic ambient noise, following the recent increase in seismic broadband network density in Portugal and Spain. Group velocities have been computed for each station pair using the empirical Green's functions generated by cross-correlating one-day-length seismic ambient-noise records. The resulting high-path density allows us to obtain lateral variations of the group velocities as a function of period in cells of 0.5 degrees x 0.5 degrees with an unprecedented resolution. As a result we were able to address some of the unknowns regarding the lithospheric structure beneath SW Iberia. The dispersion maps allow the imaging of the major structural units, namely the Iberian Massif, and the Lusitanian and Algarve Meso-Cenozoic basins. The Cadiz Gulf/Gibraltar Strait area corresponds to a strong low-velocity anomaly, which can be followed to the largest period inverted, although slightly shifted to the east at longer periods. Within the Iberian Massif, second-order perturbations in the group velocities are consistent with the transitions between tectonic units composing the massif. (C) 2013 Elsevier B.V. All rights reserved.

Classificação de anomalias e redução de falsos positivos em sistemas de detecção de intrusão baseados em rede utilizando métodos de agrupamento

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Interpretation of gravity data to delineate structural features connected to low-temperature geothermal resources at Northeastern Portugal

A great number of low-temperature geothermal fields occur in Northern-Portugal related to fractured rocks. The most important superficial manifestations of these hydrothermal systems appear in pull-apart tectonic basins and are strongly conditioned by the orientation of the main fault systems in the region. This work presents the interpretation of gravity gradient maps and 3D inversion model produced from a regional gravity survey. The horizontal gradients reveal a complex fault system. The obtained 3D model of density contrast puts into evidence the main fault zone in the region and the depth distribution of the granitic bodies. Their relationship with the hydrothermal systems supports the conceptual models elaborated from hydrochemical and isotopic water analyses. This work emphasizes the importance of the role of the gravity method and analysis to better understand the connection between hydrothermal systems and the fractured rock pattern and surrounding geology. (c) 2013 Elsevier B.V. All rights reserved.

Concepção de um reactor batch multifunções

Mestrado em Engenharia Química