Distribution kinetics of solutes in the isolated in-situ perfused rat head using the multiple indicator dilution technique and a physiological two-barrier model

The purpose of this study was to determine the pharmacokinetics of [C-14]diclofenac, [C-14]salicylate and [H-3]clonidine using a single pass rat head perfusion preparation. The head was perfused with 3-[N-morpholino] propane-sulfonic acid-buffered Ringer's solution. Tc-99m-red blood cells and a drug were injected in a bolus into the internal carotid artery and collected from the posterior facial vein over 28 min. A two-barrier stochastic organ model was used to estimate the statistical moments of the solutes. Plasma, interstitial and cellular distribution volumes for the solutes ranged from 1.0 mL (diclofenac) to 1.6 mL (salicylate), 2.0 mL (diclofenac) to 4.2 mL (water) and 3.9 mL (salicylate) to 20.9 mL (diclofenac), respectively. A comparison of these volumes to water indicated some exclusion of the drugs from the interstitial space and salicylate from the cellular space. Permeability-surface area (PS) products calculated from plasma to interstitial fluid permeation clearances (CLPI) (range 0.02-0.40 mL s(-1)) and fractions of solute unbound in the perfusate were in the order: diclofenac>salicylate >clonidine>sucrose (from 41.8 to 0.10 mL s(-1)). The slow efflux of diclofenac, compared with clonidine and salicylate, may be related to its low average unbound fraction in the cells. This work accounts for the tail of disposition curves in describing pharmacokinetics in the head.

Simulation of the load-unload response ratio and critical sensitivity in the lattice solid model

The Load-Unload Response Ratio (LURR) method is an intermediate-term earthquake prediction approach that has shown considerable promise. It involves calculating the ratio of a specified energy release measure during loading and unloading where loading and unloading periods are determined from the earth tide induced perturbations in the Coulomb Failure Stress on optimally oriented faults. In the lead-up to large earthquakes, high LURR values are frequently observed a few months or years prior to the event. These signals may have a similar origin to the observed accelerating seismic moment release (AMR) prior to many large earthquakes or may be due to critical sensitivity of the crust when a large earthquake is imminent. As a first step towards studying the underlying physical mechanism for the LURR observations, numerical studies are conducted using the particle based lattice solid model (LSM) to determine whether LURR observations can be reproduced. The model is initialized as a heterogeneous 2-D block made up of random-sized particles bonded by elastic-brittle links. The system is subjected to uniaxial compression from rigid driving plates on the upper and lower edges of the model. Experiments are conducted using both strain and stress control to load the plates. A sinusoidal stress perturbation is added to the gradual compressional loading to simulate loading and unloading cycles and LURR is calculated. The results reproduce signals similar to those observed in earthquake prediction practice with a high LURR value followed by a sudden drop prior to macroscopic failure of the sample. The results suggest that LURR provides a good predictor for catastrophic failure in elastic-brittle systems and motivate further research to study the underlying physical mechanisms and statistical properties of high LURR values. The results provide encouragement for earthquake prediction research and the use of advanced simulation models to probe the physics of earthquakes.

Effects of BDF 9198 on left ventricular contractility in advanced spontaneously hypertensive rats with heart failure

In the first part of this study, we characterized 24-month-old Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs), their heart weights, and the responses of the isolated left ventricles to electrical stimulation. In the main part of the study, we tested whether the positive inotropic effects of BDF 9198, which prevents the closure of the cardiac sodium channel, were present in senescence and heart failure. Thus, we studied the effects of BDF 9198 on the left ventricle strips of 24-month-old WKY rats (senescence) and SHRs using contractility methods. In comparison with WKY rats, the left ventricles of 24-month-old SHRs were hypertrophied and had prolonged times to peak contraction. BDF 9198 (10(-8) to 10(-6) m) was a positive inotrope on the left ventricles of WKY rats, with a maximum augmenting effect of 122% with BDF 9198 at 10(-7) m. The magnitude of the augmenting effects of BDF 9198 were reduced in SHR heart failure, with a maximum augmenting effect of 26% at 10(-7) m. BDF 9198 at 10(-6) m attenuated the responses of the SHR left ventricle to electrical stimulation. In conclusion, the potential of drugs that prevent closure of the sodium channel as positive inotropes in the treatment of heart failure should be further considered.

Oceanic interchange and nonequilibrium population structure in the estuarine dependent Indo-Pacific tasselfish, Polynemus sheridani

We assayed mtDNA haplotype [300 base pairs (bp) control region] geography and genealogy in the Indo-Pacific tasselfish, Polynemus sheridani from its contiguous estuarine distribution across northern Australia (n = 169). Eight estuaries were sampled from three oceanographic regions (Timor Sea, Gulf of Carpentaria and the Coral Sea) to assess the impact of Pleistocene sea level changes on the historical connectivity among P. sheridani populations. Specifically, we investigated the genetic consequences of disruption to Indian-Pacific Ocean connectivity brought about by the closure of the Torres Strait. Overall there was significant population subdivision among estuaries (F-ST = 0.161, (Phi(ST) = 0.187). Despite a linear distribution, P. sheridani did not show isolation by distance over the entire sampled range because of genetic similarity of estuaries greater than 3000 km apart. However, significant isolation by distance was detected between estuaries separated by less than 3000 km of coastline. Unlike many genetic studies of Indo-Pacific marine species, there was no evidence for an historical division between eastern and western populations. Instead, phylogeographical patterns were dominated by a starlike intraspecific phylogeny coupled with evidence for population expansion in both the Gulf of Carpentaria and the Coral Sea but not the Timor Sea. This was interpreted as evidence for recent west to east recolonization across of northern Australia following the last postglacial marine advance. We argue that although sufficient time has elapsed postcolonization for populations to approach gene flow-drift equilibrium over smaller spatial scales (< 3000 km), the signal of historical colonization persists to obscure the expected equilibrium pattern of isolation by distance over large spatial scales (> 3000 km).

What happens after the swallow? Introducing the glottal release sound

Cervical auscultation presents as a noninvasive screening assessment of swallowing. Until now the focus of acoustic research in swallowing has been the characterization of swallowing sounds,. However, it may be that the technique is also suitable for the detection of respiratory sounds post swallow. A healthy relationship between swallowing and respiration is widely accepted as pivotal to safe swallowing. Previous investigators have shown that the expiratory phase of respiration commonly occurs prior to and after swallowing. That the larynx is valved shut during swallowing is also accepted. Previous research indicates that the larynx releases valved air immediately post swallow in healthy individuals. The current investigation sought to explore acoustic evidence of a release of subglottic air post swallow in nondysphagic individuals using a noninvasive medium. Fifty-nine healthy individuals spanning the ages of 18 to 60+ years swallowed 5 and 10 milliliters (ml) of thin and thick liquid boluses. Objective acoustic analysis was used to verify presence of the sound and to characterize its morphological features. The sound, dubbed the glottal release sound, was found to consistently occur in close proximity following the swallowing sound. The results indicated that the sound has distinct morphological features and that these change depending on the volume and viscosity of the bolus swallowed. Further research will be required to translate this information to a clinical tool.

Variation in articulatory timing of three English consonants: An electropalatographic investigation

Increasingly, electropalatography (EPG) is being used in speech pathology research to identify and describe speech disorders of neurological origin. However, limited data currently exists that describes normal articulatory segment timing and the degree of variability exhibited by normal speakers when assessed with EPG. Therefore, the purpose of the current investigation was to use the Reading EPG3 system to quantify segmental timing values and examine articulatory timing variability for three English consonants. Ten normal subjects repeated ten repetitions of CV words containing the target consonants /t/, /l/, and /s/ while wearing an artificial palate. The target consonants were followed by the /i/ vowel and were contained in the carrier phrase 'I saw a __'. Mean duration of the approach, closure/constriction, and release phases of consonant articulation were calculated. In addition, inter-subject articulatory timing variability was investigated using descriptive graphs and intra-subject articulatory timing variability was investigated using a coefficient of variation. Results revealed the existence of intersubject variability for mean segment timing values. This could be attributed to individual differences in the suprasegmental features of speech and individual differences in oral cavity size and structure. No significant differences were reported for degree of intra-subject variability between the three sounds for these same phases of articulation. However, when this data set was collapsed, results revealed that the closure/constriction phase of consonant articulation exhibited significantly less intra-subject variability than both the approach and release phases. The stabilization of the tongue against the fixed structure of the hard palate during the closure phase of articulation may have reduced the levels of intra-subject variability.

Numerical simulations of wind and temperature structure within an Alpine lake basin, Lake Tekapo, New Zealand

High-resolution numerical model simulations have been used to study the local and mesoscale thermal circulations in an Alpine lake basin. The lake (87 km(2)) is situated in the Southern Alps, New Zealand and is located in a glacially excavated rock basin surrounded by mountain ranges that reach 3000 m in height. The mesoscale model used (RAMS) is a three-dimensional non-hydrostatic model with a level 2.5 turbulence closure scheme. The model demonstrates that thermal forcing at local (within the basin) and regional (coast-to-basin inflow) scales drive the observed boundary-layer airflow in the lake basin during clear anticyclonic summertime conditions. The results show that the lake can modify (perturb) both the local and regional wind systems. Following sunrise, local thermal circulations dominate, including a lake breeze component that becomes embedded within the background valley wind system. This results in a more divergent flow in the basin extending across the lake shoreline. However, a closed lake breeze circulation is neither observed nor modelled. Modelling results indicate that in the latter part of the day when the mesoscale (coast-to-basin) inflow occurs, the relatively cold pool of lake air in the basin can cause the intrusion to decouple from the surface. Measured data provide qualitative and quantitative support for the model results.

A coupled knowledge-based expert system for design of liquid-retaining structures

This paper describes a coupled knowledge-based system (KBS) for the design of liquid-retaining structures, which can handle both the symbolic knowledge processing based on engineering heuristics in the preliminary synthesis stage and the extensive numerical crunching involved in the detailed analysis stage. The prototype system is developed by employing blackboard architecture and a commercial shell VISUAL RULE STUDIO. Its present scope covers design of three types of liquid-retaining structures, namely, a rectangular shape with one compartment, a rectangular shape with two compartments and a circular shape. Through custom-built interactive graphical user interfaces, the user is directed throughout the design process, which includes preliminary design, load specification, model generation, finite element analysis, code compliance checking and member sizing optimization. It is also integrated with various relational databases that provide the system with sectional properties, moment and shear coefficients and final member details. This system can act as a consultant to assist novice designers in the design of liquid-retaining structures with increase in efficiency and optimization of design output and automated record keeping. The design of a typical example of the liquid-retaining structure is also illustrated. (C) 2003 Elsevier B.V All rights reserved.

Electropalatographic assessment of tongue-to-palate contacts exhibited in dysarthria following traumatic brain injury: Spatial characteristics

Consonant imprecision has been reported to be a common feature of the dysarthric speech disturbances exhibited by individuals who have sustained a traumatic brain injury (TBI). Inaccurate tongue placements against the hard palate during consonant articulation may be one factor underlying the imprecision. To investigate this hypothesis, electropalatography (EPG) was used to assess the spatial characteristics of the tongue-to-palate contacts exhibited by three males (aged 23-29 years) with dysarthria following severe TBI. Five nonneurologically impaired adults served as control subjects. Twelve single-syllable words of CV or CVC construction (where initial C = /t, d, S, z, k, g/, V=/i, a/) were read aloud three times by each subject while wearing an EPG palate. Spatial characteristics were analyzed in terms of the location, pattern, and amount of tongue-to-palate contact at the frame of maximum contact during production of each consonant. The results revealed that for the majority of consonants, the patterns and locations of contacts exhibited by the TBI subjects were consistent with the contacts generated by the group of control subjects. One notable exception was one subject's production of the alveolar fricatives in which complete closure across the palate was demonstrated, rather than the characteristic groove configuration. Major discrepancies were also noted in relation to the amount of tongue-to-palate contact exhibited, with two TBI subjects consistently demonstrating increased contacts compared to the control subjects. The implications of these findings for the development of treatment programs for dysarthric speech disorders subsequent to TBI are highlighted.

As novas formas de explora????o do trabalho no capitalismo contempor??neo e as pol??ticas p??blicas de combate ?? desigualdade

O mercado de trabalho sofreu profundas transforma????es desde o come??o do capitalismo at?? o momento atual, sendo poss??vel compar??-lo a uma loteria, na qual os trabalhadores passaram a competir entre si por ascens??o profissional. Os bilhetes dessa loteria s??o os investimentos em capital humano. Nela haver??, necessariamente, vencedores e perdedores, com os primeiros apropriando-se do trabalho dos ??ltimos. Dessa realidade, surge uma nova forma de explora????o do trabalho, cujo instrumento de legitima????o ?? o capital humano, que refor??a a tend??ncia inerente do capitalismo ?? gera????o de desigualdade e coloca limita????es ?? vis??o tradicional de combate ?? desigualdade baseada na democratiza????o do capital humano. O crescimento tamb??m tem limita????es na redu????o da desigualdade, tendo em vista que a motiva????o microecon??mica que gera o crescimento macroecon??mico ?? justamente a busca pela desigualdade.

Avan??os desiguais e inten????es indefinidas: a reforma do estado do M??xico e a estrat??gia de gerenciamento

Este paper defende duas id??ias. A primeira, ?? apresentar os diferentes processos da reforma do Estado mexicano, analisados sob as prioridades diversas no decorrer do tempo. As reformas econ??mica, pol??tica, social e administrativa tiveram prioridades e objetivos divergentes. A reforma econ??mica foi sistem??tica e congruente, a pol??tica foi defensiva e pouco abrangente, e a social foi problem??tica e confusa. A reforma administrativa foi, comparativamente, limitada. Uma proposta para desenvolver um sistema administrativo respons??vel pelo servi??o p??blico foi postergada nos ??ltimos 12 anos at?? que, em maio de 1997, finalmente a atual administra????o prop??s um programa de moderniza????o. A segunda id??ia ?? que, mesmo que a atual administra????o tenha a inten????o de desenvolver um novo sistema de accountability e um plano de carreira para o servi??o p??blico, parece plaus??vel que a tradicional pol??tica de controle, atrav??s da estrutura administrativa, possa ser prejudicada se essas propostas realmente reduzirem o poder discricion??rio dos altos cargos p??blicos e submeterem reservas p??blicas a um esquema de controle social mais aberto e formal. Logo, ?? poss??vel dizer que a alternativa escolhida pelos reformistas foi usar uma abordagem gerenciadora, onde a melhoria dos procedimentos e a implementa????o de algumas t??cnicas administrativas avan??adas substituem, pelo menos at?? agora, uma transforma????o mais profunda da estrutura administrativa. Uma estrat??gia de gerenciamento permite, pelo menos at?? o momento, a melhoria dos servi??os atrav??s do aumento da participa????o de servidores p??blicos, sem prejudicar a atual administra????o, como um instrumento para implementar diferentes agendas pol??ticas usando recursos p??blicos. Nosso argumento ?? que, como o programa de moderniza????o est?? sendo implantado, ?? importante estudar minuciosamente as possibilidades de se implementar a reforma do servi??o p??blico e melhorar a responsabilidade do sistema, dada a particular rela????o que existe entre a administra????o p??blica e o sistema pol??tico no M??xico.

Interven????o estatal, centraliza????o pol??tica e reforma burocr??tica: o significado dos departamentos administrativos no Estado Novo

O objetivo deste artigo ?? expor e explicar um momento espec??fico da evolu????o pol??tico institucional brasileira. S??o explorados os conflitos que est??o na origem da escolha e a implementa????o de uma nova ordem pol??tico-administrativa no p??s-1930. S??o examinadas as origens, a concep????o e os objetivos que guiaram a inven????o de um aparelho burocr??tico que, juntamente com o interventor federal, n??o s?? controlou as elites pol??ticas regionais, mas tamb??m contribuiu para a organiza????o do poder do Estado em bases nacionais, cooperando para viabilizar a capacidade estatal: os Departamentos Administrativos. Analiso o contexto pol??tico, os antecedentes legais e as inova????es institucionais do decreto-lei n?? 1202/39, a fim de responder a duas quest??es bem espec??ficas: por que e com que objetivo essa lei sobre a administra????o dos estados e dos munic??pios foi criada durante o Estado Novo?

Aprender a governar: a aprendizagem de funcion??rios p??blicos para as carreiras de estado

Esta tese investiga como dois grupos de funcion??rios p??blicos seleciona dos para as carreiras de Estado no Brasil aprendem a desempenhar as suas fun????es. Deste m odo, busca compreender os processos de aprendizagem, formais e informais, da e ntrada desses servidores p??blicos como alunos nos espa??os destinados ?? sua forma????o, at?? sua inser ????o nos espa??os de trabalho, como aprendizes. A pesquisa justifica-se porque, sendo as am ostras estudadas consideradas boas refer??ncias no servi??o p??blico, faz-se necess??ri o compreender como se d?? a aprendizagem para o exerc??cio dessas carreiras de Estado. Quatro dimens??es s??o consideradas para investigar a aprendizagem dos funcion??rios p??blicos: primeira, o surgimento e evolu????o da forma????o em administra????o p??bli ca no Pa??s. Segunda, as escolas de governo, lugares prop??cios ?? aprendizagem, influente s para a administra????o p??blica do Pa??s, inclinados ?? discuss??o de novas solu????es e cr??ticos na identifica????o, an??lise e apropria????o das experi??ncias verificadas em outras realidades. Te rceira, os cursos de forma????o inicial, espa??os para o primeiro contato com a fun????o escol hida e os seus desafios, saberes necess??rios e ferramentas dispon??veis. Quarta, a inse r????o no ambiente de trabalho, decisiva para o processo de aprendizagem social dos funcion??rios novatos por interm??dio das comunidades de pr??tica.